Prognosis in early stage cutaneous T-cell lymphoma treated with psoralen plus ultraviolet A irradiation and low-dose interferon-α: Long-term efficacy and survival according to conventional and emerging clinical endpoints.

Patients with early stage cutaneous T cell lymphoma (CTCL) usually have a benign and chronic disease course, characterized by temporally response to conventional skin directed therapies and intrinsic possibility to evolve. Using the combination of psoralen plus ultraviolet A irradiation (PUVA) and low-dose interferon-α (INF), the principal treatment goal is to keep confined the disease to the skin, preventing disease progression. Among 87 patients with early stage IA to IIA MF treated with low-dose IFN-α2b and PUVA in our center, complete remission (CR) were reported in 70 patients (80.5%) and the overall response rate (ORR) was 97.8% (n = 85), with a median time to best response to therapy of 5 months (range, 1-30). Among the responders, only the 8% of patients had a relapse with major event. The median follow-up was 207 months (range, 6-295). Survival data showed a median overall survival (OS) not reached (95% CI; 235-NR months), a disease free survival (DFS) of 210 months (95% CI; 200-226 months) and a median time to next treatment (TTNT) of 38.5 months (95% CI, 33-46 months). The long follow up of this study verifies our preliminary results already published in 2006 and confirms the efficacy of INF-PUVA combination therapy in a real world setting, according conventional (OS and DFS) and emerging (TTNT) clinical endpoint of treatment efficacy.

Italian expert-based recommendations on the use of photo(chemo)therapy in the management of mycosis fungoides: Results of an e-Delphi consensus.

BACKGROUND: Phototherapy is a mainstay for the treatment of MF. However, there is scarce evidence for its use, mostly due to the lack of a unified schedule. AIMS: The primary aim of this study was to establish the first structured, expert-based consensus regarding the indications and technical schedules of NB-UVB and PUVA for MF. The secondary aim was to determine the consensus level for each specific item. MATERIALS & METHODS: E-delphi study. Item-specific expert consensus was defined as the number of "Totally Agree" results to ≥80% of the panelists. Cronbach alpha index ≥0.7 was used as a measure of homogeneity in the responses among questions related to the same topic. RESULTS: Overall, there was a high homogeneity among responders (0.78). On specific topics, the highest grade was observed for technical items (0.8) followed by indications for early (0.73) and advanced stages (0.7). CONCLUSIONS: Items related to the most canonical indications of phototherapy and to treatment schedules showed the highest agreements rates. There is consensus about the use of standardized treatment schedules for the induction and consolidation phases for NB-UVB and PUVA in MF.

Analysis of Sentinel Node Biopsy and Clinicopathologic Features as Prognostic Factors in Patients With Atypical Melanocytic Tumors.

BACKGROUND: Atypical melanocytic tumors (AMTs) include a wide spectrum of melanocytic neoplasms that represent a challenge for clinicians due to the lack of a definitive diagnosis and the related uncertainty about their management. This study analyzed clinicopathologic features and sentinel node status as potential prognostic factors in patients with AMTs. PATIENTS AND METHODS: Clinicopathologic and follow-up data of 238 children, adolescents, and adults with histologically proved AMTs consecutively treated at 12 European centers from 2000 through 2010 were retrieved from prospectively maintained databases. The binary association between all investigated covariates was studied by evaluating the Spearman correlation coefficients, and the association between progression-free survival and all investigated covariates was evaluated using univariable Cox models. The overall survival and progression-free survival curves were established using the Kaplan-Meier method. RESULTS: Median follow-up was 126 months (interquartile range, 104-157 months). All patients received an initial diagnostic biopsy followed by wide (1 cm) excision. Sentinel node biopsy was performed in 139 patients (58.4%), 37 (26.6%) of whom had sentinel node positivity. There were 4 local recurrences, 43 regional relapses, and 8 distant metastases as first events. Six patients (2.5%) died of disease progression. Five patients who were sentinel node-negative and 3 patients who were sentinel node-positive developed distant metastases. Ten-year overall and progression-free survival rates were 97% (95% CI, 94.9%-99.2%) and 82.2% (95% CI, 77.3%-87.3%), respectively. Age, mitotic rate/mm2, mitoses at the base of the lesion, lymphovascular invasion, and 9p21 loss were factors affecting prognosis in the whole series and the sentinel node biopsy subgroup. CONCLUSIONS: Age >20 years, mitotic rate >4/mm2, mitoses at the base of the lesion, lymphovascular invasion, and 9p21 loss proved to be worse prognostic factors in patients with ATMs. Sentinel node status was not a clear prognostic predictor.

Identifying locally advanced basal cell carcinoma eligible for treatment with vismodegib: an expert panel consensus.

Basal cell carcinoma (BCC) is the most common skin cancer worldwide. Most occur on the head and neck, where cosmetic and functional outcomes are critical. BCC can be locally destructive if not diagnosed early and treated appropriately. Surgery is the treatment of choice for the majority of high-risk lesions. Aggressive, recurrent or unresectable tumors can be difficult to manage. Until recently, no approved systemic therapy was available for locally advanced or metastatic BCC inappropriate for surgery or radiotherapy. Vismodegib provides a systemic treatment option. However, a consensus definition of advanced BCC is lacking. A multidisciplinary panel with expertise in oncology, dermatology, dermatologic surgery and radiation oncology proposes a consensus definition based on published evidence and clinical experience.

Defining the Profile of Patients with Primary Merkel Cell Carcinoma in Central Italy: A Retrospective Analysis.

Merkel cell carcinoma (MCC) is a rare neuroendocrine skin cancer that usually occurs in elderly people on sun-exposed areas, with a predisposition to local recurrence. Evidence suggests a growing incidence over the past decade; however, robust epidemiologic data are still lacking. We describe the MCC population in clinical practice in a retrospective analysis of demographic, clinical, and tumor characteristics from medical records of primary MCC patients, between 2015 and 2020, at six dermatology clinics in Central Italy. Ninety-four patients were included (57.4% male; mean age 78.2 ± 10.1 years, range 47-99 years). The estimated incidence rate of MCC was 0.93 per 100,000 inhabitants/year. Lower limbs were the most frequently affected site (31.5%), and 54% of patients for whom information was available were immunosuppressed. Lymph node involvement was reported in 42.5% of patients, and distant metastases in almost 20%. Most patients underwent surgery for tumor excision and were mainly referred to specialized dermatology clinics by dermatologists (47.9%) and general surgeons (28.7%). Apart from the relatively balanced prevalence of MCC in men and women, the predominant location on lower limbs, and the higher incidence rate compared with previous reports in Italy, this population is, overall, similar to the populations described in other observational studies. MCC management requires the involvement of several specialties. Increased awareness of MCC and standardization of its management are urgently needed.

Mental Health Consequences of the COVID-19 Pandemic Long-Term Exposure in Italian Dermatologists.

The present study aimed at assessing the consequences of prolonged exposure to COVID-19 distress on mental health in non-frontline health care workers. For this purpose, we have conducted a survey on 425 Italian dermatologists, in the period February-March 2021. The psychopathological symptoms, depression, anxiety, post-traumatic stress symptoms (PTSD), as well as resilience, have been evaluated. The main factors that influence the physician's psychological health have been also investigated. Our study showed that the physicians older than 40 years, as well as those who lived this period in company, reported more personal resources, better managing the distress. Resilience, COVID-19 beliefs, COVID-19 working difficulties, and age were the common predictors of the severe psychopathological symptoms. An interesting result is that the lower level of resilience was the most powerful predictor of a more severe depression, as well as of a higher severity of generalized anxiety disorder, but not of COVID-19 PTSD. The fear of COVID-19 was the most powerful predictor of COVID-19 PTSD. Home conditions and previous SARS-CoV2 infection constituted significant predictors of severe depressive symptoms, but not of anxiety and COVID-19 PTSD. These results are useful in a better understanding of protective and risk factors involved in COVID-19 long-term distress exposure.

Cost-effectiveness analysis of TNF-alpha blockers for the treatment of chronic plaque psoriasis in the perspective of the Italian health-care system.

The cost-effectiveness of biological treatments for psoriasis is not well determined and may vary from country to country. The objectives of this study was to perform a cost-effectiveness analysis of infliximab compared with other anti-tumor necrosis factor-alpha agents for the treatment of psoriasis in Italy. The incremental cost-effectiveness ratio per patients achieving at least 75% improvement in the psoriasis area and severity index assessed over 24- and 48-50-week periods was calculated. Efficacy data were drawn from randomized controlled trials when available or from open label studies. Considering patients achieving psoriasis area and severity index at week 24 and 48-50, infliximab was dominant (more effective and less costly) over etanercept given at 50 mg twice weekly. In contrast, infliximab was not dominant over etanercept at other dosages or over adalimumab. When considering the impact of therapy on quality of life at Week 12 using the Dermatology Life Quality Index equal to zero, infliximab resulted more effective and less costly than etanercept. Therefore, infliximab seems to be cost-effective in the therapy of psoriasis. Further cost-efficacy evaluations based on head-to-head trials are necessary to address health economic considerations.

Treating psoriasis with etanercept in italian clinical practice: prescribing practices and duration of remission following discontinuation.

BACKGROUND: conventional antipsoriatic therapies are often administered until remission, with treatment resumed in the case of relapse, in order to reduce the likelihood of cumulative, dose-dependent toxicities. Biological agents have been safely used in continuous therapy. OBJECTIVE: to assess the use of etanercept for psoriasis in clinical practice in Italy. METHODS: this was an observational study carried out in 13 dermatological centres across Italy in patients with plaque psoriasis (with a Psoriasis Area and Severity Index [PASI] score >or=10) treated with etanercept. The study comprised a treatment and subsequent discontinuation period. Patients were eligible if they had plaque psoriasis and had begun treatment with etanercept between 1 September 2007 and 1 April 2008. Patients were evaluable for the duration of discontinuation analysis if they achieved a PASI reduction >or=50% (PASI50) and a PASI score <10 at the end of treatment. Etanercept treatment was restarted if the PASI score reached >or=10 or the patient had a clinical relapse. Data were collected retrospectively up to June 2008 and prospectively between July 2008 and January 2009. Patients received etanercept during the treatment period, followed by no etanercept treatment (other psoriasis treatment permitted) during the discontinuation period, and etanercept again during re-treatment. The main outcome measures were: PASI scores (type A responders: PASI reduction >or=75% [PASI75]; type B responders: PASI50 and PASI final score <10), Dermatology Life Quality Index (DLQI) scores and body surface area (BSA) involvement. Time from discontinuation to re-treatment was evaluated. Use of other antipsoriatic medications was recorded throughout. RESULTS: eighty-five patients were evaluable for the treatment period. Overall, 55 (64.7%) of these patients were prescribed etanercept 50 mg twice weekly. The mean treatment duration was approximately 25 weeks. In total, 79 patients (92.9%) were considered type B responders and 77 of these patients were evaluable for the duration of discontinuation analysis. Overall, 68/85 (80%) were type A responders. During the treatment period, 7/85 (8.2%) patients received other antipsoriatic therapies. Improvements in mean DLQI score (-71.5%) and mean BSA involvement (-79.2%) were also observed. Etanercept was well tolerated. During the discontinuation period, 40/77 (51.9%) patients used other antipsoriatic medications (group 1) and 37/77 (48.1%) did not (group 2). The mean duration of discontinuation was significantly longer in group 1 (174 days) than in group 2 (117 days, log-rank test: p = 0.0013). CONCLUSION: in clinical practice, the duration of discontinuation from etanercept was in accordance with previously reported data, and was longer in patients who received other antipsoriatic drugs during discontinuation of etanercept than in those who did not. High rates of PASI50 and PASI75 response were obtained with etanercept, and these rates were higher than those observed in controlled clinical studies. Etanercept treatment was flexible, effective and well tolerated, and was associated with improved quality of life.

Sunburn-related variables, secular trends of improved sun protection and short-term impact on sun attitude behavior in Italian primary schoolchildren: Analysis of the educational campaign "Il Sole Amico" ("The sun as a friend").

Sun protection early in life is an essential issue for primary prevention of skin cancers. The Il Sole per Amico was an educational campaign among 66 Italian primary schools. A total of 12,188 questionnaires were completed at baseline. Overall, 9.4% children reported >1 sunburn during the last year and 44.7% parents a use of sunlamps. Independent factors associated with sunburns were: age, lower level of parents' education, light eye and skin color, freckles, nevi on arms, intense sun exposure during the last year, sporadic use of sunscreens, and parental use of sunlamps. A total of 7280 (59.7%) questionnaires were completed at the end of the educational intervention. No significant difference was documented about behavior between the pre- and post-intervention periods. A significant reduction was instead found in both prevalence of recent sunburns and total number of sunburn episodes after comparison with the data obtained by identical questionnaire in the same geographic areas in the "Sole Si Sole No" project in 2001.

Effects of TNFα inhibitors in patients with psoriasis and metabolic syndrome: a preliminary study.

BACKGROUND: Psoriasis is an inflammatory disease, that is increasingly being considered as a systemic disorder. Among associated comorbidities, metabolic syndrome plays an important role. The effects of biological therapies on metabolic syndrome is controversial. METHODS: Thirty-one psoriatic patients with metabolic syndrome, eligible to treatment with anti-TNFα agents, were enrolled. Metabolic parameters were measured during 4 subsequent visits, one every 40 to 60 days. PASI, BSA and DLQI assessed the severity of psoriasis and the impact on quality of life. RESULTS: We include 31 patients, 18 treated with etanercept and 13 with adalimumab. Metabolic parameters evaluated at V4 in both groups showed different trends in the blood glucose values: a slight decrease in adalimumab group, an increase in etanercept group, with an almost significant comparison test (P=0.073). Similarly, the lipid profile revealed an opposing trend, with an increase in triglycerides in adalimumab patients, and a decrease in the other group, without statistically significant differences. No statistically significant difference was recorded in HDL cholesterol. An improvement in systolic and diastolic pressure was appreciated in both groups, although not significantly. The waist circumference slightly decreased in both groups. PASI 75 score was reached in 60% of the patients. In addition, BSA and DLQI improved. CONCLUSIONS: Our study showed a slight improvement of metabolic parameters, at times with a trend toward significance. Additional long-term studies and a larger number of patients are needed to more clearly define the association between psoriasis and cardiovascular disease and understand the effect of biological therapies on metabolic parameters.

When basal cell carcinomas became giant: an Italian multicenter study.

BACKGROUND: Giant basal cell carcinoma (GBCC) is a basal cell carcinoma (BCC) enlarged in a diameter more than 5 cm. Since GBCCs are a highly infrequent entity and the occurrence rate is approximately 0.5-1% out of all BCC types, only anecdotal cases are reported, and causes and characteristics inducing development of this tumor are not defined. OBJECTIVES: Evaluate causative factors and clinico-histological characteristics of GBCCs. METHODS: The study is a 6-month, hospital-based case series study performed in 12 Italian dermatologic centers. RESULTS: A total of 59 cases and 458 control BCCs were collected. No significant differences existed between the two groups if we take into account social or cultural factors. The average duration of GBCCs is considerably longer than controls. GBCCs are located on unexposed areas while BCCs are on areas not usually covered by clothes. Superficial histological subtype was more frequent in the BCCs group, while infiltrative in GBCCs. GBCCs showed significantly higher local invasiveness, and greater metastatic capacity. More than half of GBCCs had been previously treated with one or more treatments. CONCLUSIONS: Patients with GBCCs appear to belong to two categories: (i) those who present with GBCC due to delay in accessing medical attention, and (ii) those who have BCCs previously treated with inappropriate strategies. Only very few cases can be carried out with intrinsic biological features of tumor aggressiveness. Social and cultural conditions do not appear to be involved in the development of GBCCS. These observations may help clinicians in selecting correct therapeutic strategies in the treatment of BCCs, which give rise to GBCC.

Low-frequency low-intensity ultrasounds do not influence the survival and immune functions of cultured keratinocytes and dendritic cells.

Low-frequency ultrasounds (US) are used to enhance drug transdermal transport. Although this phenomenon has been extensively analyzed, information on US effects on the single skin cell components is limited. Here, we investigated the possible effects of low-frequency US on viability and immune functions of cultured human keratinocytes and dendritic cells (DC), skin cells involved in the regulation of many immune-mediated dermatoses. We demonstrated that US, employed at low-frequency (42 KHz) and low-intensity (0.15 W/cm(2)) values known to enhance drug and water transdermal transport, did not affect extracellular-signal-regulated-kinase (ERK)1/2 activation, cell viability, or expression of adhesion molecules in cultured keratinocytes. Moreover, US at these work frequency and intensity did not influence the keratinocyte expression and release of immunomodulatory molecules. Similarly, cultured DC treated with low-frequency low-intensity US were viable, and did not show an altered membrane phenotype, cytokine profile, nor antigen presentation ability. However, intensity enhancement of low-frequency US to 5 W/cm(2) determined an increase of the apoptotic rate of both keratinocytes and DC as well as keratinocyte CXCL8 release and ERK1/2 activation, and DC CD40 expression. Our study sustains the employment of low-frequency and low-intensity US for treatment of those immune skin disorders, where keratinocytes and DC have a pathogenetic role.

Switching from a biological therapy to another biologic agent in psoriatic patients: the experience of PsOMarche group.

BACKGROUND: Switching is a "hot" topic and the main reasons for switching prior biologic agent are for a primary failure, a secondary failure or drug intolerance, patient's dissatisfaction, physician decision. The aim of the study was to assess the optimization of the switching from a biologic agent to another. METHODS: Five Dermatological Units have participated to PsOMarche working group have studied thirty-eight patients affected moderate to severe chronic plaque psoriasis at time 0 (patient recruitment at time of switching from biological therapy to another), 8 weeks (T8), 16 weeks (T16). RESULTS: Twenty-eight males and 10 females were included in the study. At T0, 18 of 22 patients treated with etanercept had been switched to adalimumab and 4 to ustekinumab. Among 10 patients treated with adalimumab, 5 had been switched to ustekinumab, 2 to golimumab and 3 to certolizumab pegol. One patient treated with Infliximab and 5 patients treated with ustekinumab had been switched to adalimumab. Switching had been performed for primary inefficacy in 9 patients (23.6%) and a secondary failure was evidenced in 29 patients (73.4%). PASI75 was achieved in 53% and in 89.4% of patients after 8 weeks and 16 weeks of switching to the second biologic agent respectively; similarly, PsoDISK score significantly decreased at T8 and T16. CONCLUSIONS: The experience of PsOMarche group have shown that the switching to a biologic agent to another is a valuable treatment choice in patients with moderate to severe psoriasis experiencing a treatment failure with one biologic therapy, leading to a good improvement in skin disease and in patient's quality of life.

Pegylated liposomal doxorubicin in the treatment of primary cutaneous T-cell lymphomas.

Pegylated liposomal doxorubicin (Peg-Doxo) is a promising drug for advanced/recalcitrant primary cutaneous T-cell lymphomas (CTCLs). This prospective phase II trial enrolled 19 patients. We observed overall and complete response rates of 84.2% and 42.1% (with no significant differences between stage I-IIA and IIB-IV patients), and 11% grade III/IV toxicity. After a maximum 46 month-follow-up, median overall (OS), event-free (EFS) and progression-free (PFS) survival were 34, 18 and 19 months. OS, EFS and PFS rates at 46 months were 44%, 30% and 37% respectively. Peg-Doxo seems to be an active and safe principle that should be used in plurirelapsed, early stage-MF and in combination with other chemotherapeutic agents in advanced and aggressive CTCLs.

Results of a prospective phase II trial with oral low-dose bexarotene plus photochemotherapy (PUVA) in refractory and/or relapsed patients with mycosis fungoides.

INTRODUCTION: Bexarotene is a synthetic retinoid effective in early and advanced stages of mycosis fungoides (MF)/Sezary Syndrome (SS) both in monotherapy and combination schemes. We aimed to assess disease response to low-dose bexarotene and PUVA in maintenance in refractory and/or resistant patients with early and advanced stage MF/SS. METHODS: We followed prospectively 21 patients (stages IB-IV): 15 with early stage MF and 6 with advanced disease. "Mini" and standard protocols were respectively applied to patients who failed PUVA or several systemic regimens. The dose of bexarotene and the administration of PUVA were titrated individually and tailored during induction and maintenance according to previous therapy, disease stage and toxicity. We evaluated overall response (OR) at the end of maintenance, safety and event-free survival (EFS). RESULTS: After induction phase, OR was 85.6%, higher in early MF (93.4%) than in advanced disease (66.6%). At the end of maintenance, OR was 76.2%, including 33.3% of CR. Median EFS for the whole group was 31 months. Bexarotene was well tolerated regarding the side effects, with prophylaxis and progressive drug increase in the induction phase of the protocol. Side effects were mainly of low and moderate grades. CONCLUSIONS: We observed a favorable rate of therapeutic effects and few, generally mild, side effects with low doses of bexarotene combined with PUVA.

The transitioning from conventional therapy to biological treatment in psoriatic patients: STRATOS, a project of Marche Region.

BACKGROUND: STRATOS is the acronym of the "STRuctured Approach to the Treatment of psOriatic patientS". The optimization of the psoriasis's therapeutic management is one of the most important goals for dermatologists. According to Mrowietz's consensus report, the transitioning from conventional therapy to biological therapy is mainly due to the lack/loss of efficacy and/or for safety reasons. The aim of the manuscript was to describe the principal results obtained by the Dermatologic Clinic of Polytechnic University of Marche Region and the Units of Dermatology of the Marche Region applying, in our regional reality, Mrowietz's protocol for the daily management of patients with moderate-to-severe plaque. METHODS: Forty-seven patients with moderate to severe chronic plaque psoriasis have been monitored during the six-months study period. RESULTS: Psoriatic patients with diabetes showed further concomitant comorbidities compared to non-diabetics, as hypertension and hypercholesterolemia. Moreover, based on WHO classification, overweight was diagnosed in female patients, whereas obesity was prevalent in male patients. This aspect confirms the strict link between the multifaceted aspects of psoriatic patient which is primarily related to the persistent low-grade inflammation. In our psoriatic group, 10% of monitored patients were affected by Crohn disease or ulcerative colitis. CONCLUSIONS: The Mrowietz's transitioning protocol is a useful, reliable and feasible tool to manage the therapeutic iter of psoriatic patients in an Italian clinical setting also at regional level.

Relationship between cause of referral and diagnostic outcome in pigmented lesion clinics: a multicentre survey of the Italian Multidisciplinary Group on Melanoma (GIPMe).

Pigmented lesion clinics (PLCs) are permanent units to which subjects presenting with suspicious pigmented skin lesions can be rapidly referred and which can provide a prompt response to an individual's concern about melanoma. However, little is known about the melanoma detection rate in these clinics, in particular with regard to intermediate risk populations. We report a survey involving more than 1000 subjects consecutively referred by family doctors to six Italian PLCs. Using a histological diagnosis of melanoma as the endpoint, the pooled melanoma detection rate at these PLCs was 1.5% (one melanoma for diagnosed every 64 subjects examined), and the ratio between the number of melanomas and benign lesions excised for diagnostic verification was 1: 5.8 (16 melanomas and 93 benign lesions). Almost all the melanomas (15 out of 16) were detected in subjects who had requested referral for a specific doubtful lesion (group A) or for the presence of melanoma risk factors (previous melanoma, large number of common and atypical naevi, family history of melanoma) (group B). Only one melanoma was detected amongst the 418 subjects seeking consultation for concern about their moles (group C) (P = 0.004). The positive and negative predictive values of the referral groups A and B combined were 2.5% and 99.7%, respectively. Since the probability of detecting a melanoma in subjects referred only for reassurance about their moles, which nevertheless represented 43% of the subjects examined, is very low, an optimized role for PLCs in melanoma prevention would be to limit consultation to subjects who present for examination of a specific lesion or who have one or more risk factors for melanoma.