Drug survival, effectiveness and safety of ixekizumab for moderate-to-severe psoriasis up to 5 years.

INTRODUCTION: Ixekizumab proved to be effective and safe for psoriasis treatment in several randomized clinical trials and real-life studies. Nevertheless, long-term real-world experiences are still lacking, with little data up to 4 years of treatment. OBJECTIVES: To analyse survival, effectiveness and safety of ixekizumab in a real-life cohort of patients affected by moderate-to-severe psoriasis or psoriatic arthritis up to 260 weeks (5 years). METHODS: We included all patients treated with ixekizumab from December 2017 to March 2021. Drug survival (DS) was analysed in patients at risk for up to 5 years. Cox analysis was adopted to evaluate possible predictive factors of discontinuation. Psoriasis Area Severity Index (meanPASI and PASI100, 90, and ≤3) was used as outcomes of effectiveness on observed patients at 16, 52, 104, 156, 208 and 260 weeks. Logistic regression was performed to identify possible predictive factors of response. RESULTS: DS was 65.5% at 260 weeks, with being a super-responder patient (achievement of PASI100 at 16 weeks and maintained at 28 weeks) correlated with less risk of discontinuation. PASI100, 90 and ≤3 was achieved by 54.1%, 60.5% and 73% of observed patients, respectively, at 16 weeks, and by 59.1%, 81.8% and 95.5%, respectively, at 260 weeks. High mean BMI was the only factor strongly associated with less achievement of the outcomes at the earlier time points: PASI100 at 16 weeks (OR 0.93, CI 0.87-0.98, p = 0.014) and at 104 weeks (OR 0.91, CI 0.84-0.98, p = 0.019), PASI90 achievement at 16 weeks (OR 0.94, CI 0.88-0.99, p = 0.028) and 104 weeks (OR 0.91, CI 0.83-0.99, p = 0.027), and PASI ≤3 (OR 0.86, CI 0.76-0.97, p = 0.018) at 104 weeks. No severe adverse events were observed. CONCLUSIONS: Ixekizumab showed high effectiveness and safety for up to 5 years, with survival of 2/3 of treated patients. Rapid response to treatment is predictive of long-term response.

Clinicopathological definition, management and prognostic value of mogamulizumab-associated rash and other cutaneous events: A systematic review.

Mogamulizumab is a first-in-class IgG1k monoclonal antibody that selectively targets the chemokine receptor type 4. The drug has received Food and Drug administration authorisation for mycosis fungoides and Sézary syndrome following failure of at least one previous course of systemic therapy and now is available in Europe. One of the most common treatment-related side effects observed has been the mogamulizumab-associated rash (MAR), which affects up to a quarter of patients and is the most frequent adverse event leading to drug discontinuation. The aim of this study is to perform a systematic review of the literature on patients diagnosed with MAR and other mogamulizumab-related cutaneous events to describe the clinical and histological characteristics, the management in clinical practice and to assess whether these events have prognostic implications. In total, 2073 records were initially identified through a literature search, 843 of which were duplicates. After screening for eligibility and inclusion criteria, 49 articles reporting mogamulizumab-associated cutaneous events were included. Totally, 1516 patients were retrieved, with a slight male prevalence as for the available data (639 males and 570 females, i.e. 52.9% vs. 47.1%). Regarding the reported clinicopathological findings of the cutaneous reactions, the five most common patterns were spongiotic/psoriasiform dermatitis (22%), eruptions characterized by the presence of papules and/or plaques (16.1%), cutaneous granulomatosis (11.4%), morbilliform or erythrodermic dermatitis (9.4%) and photodermatitis (7.1%). Our results highlight how the majority of the reported cutaneous adverse events on mogamulizumab are of mild-to-moderate entity and generally manageable in clinical practice, though prompt recognition is essential and case-by-case assessment should be recommended. Future research will need to focus on the MAR prognostic implications and to identify genomic and molecular markers for a more rapid and accurate diagnosis.

Real-life effectiveness and safety of baricitinib in patients with severe alopecia areata: A 24-week Italian study.

BACKGROUND: Alopecia areata is an autoimmune condition characterized by rapid hair loss in the scalp, eyebrows and eyelashes, for which treatments are limited. Baricitinib, an oral inhibitor of Janus kinases 1 and 2, has been recently approved to treat alopecia areata. MATERIALS AND METHODS: We conducted a retrospective study involving 23 medical centres across Italy, enrolling patients affected by severe alopecia areata (SALT >50), for more than 6 months. Clinical and trichoscopic assessment was performed at each visit and impact on quality of life, anxiety and depression were evaluated using the Skindex-16 and the Hospital Anxiety and Depression Scale (HADS), respectively. RESULTS: A total of 118 patients were enrolled, with a mean age of 39 years and a mean SALT >95. The mean value of the SALT score decreased from an average of 96.6 (±8.23 sd) to 48 (±35.2 sd) after 24 weeks of treatment and 42.3% of patients achieved a SALT 30, 31.3% a SALT 20 and 20.3% a SALT 10 by Week 24. Trichoscopic signs showed fewer yellow dots and black dots significantly earlier than hair regrowth. Adverse events during the treatment period (mild laboratory test abnormalities) were reported in 12.7% patients. No drop-out were registered. CONCLUSION: Data on the effectiveness and safety of baricitinib are promising and support the use of this drug in severe forms of AA, also in the early stages. We also suggest performing trichoscopy in order to reveal early response to therapy.

Multicenter analysis of the surgical management and adjuvant therapy of patients with melanoma and a positive sentinel lymph node biopsy. / Análisis multicéntrico del manejo quirúrgico y tratamiento adyuvante de los pacientes con melanoma y positividad en la biopsia selectiva del ganglio centinela.

INTRODUCTION: Complete lymph node dissection (CLND) was the standard practice for patients with melanoma and a positive sentinel lymph node biopsy (SLNB) until the results of 2 clinical trials published in 2016 and 2017 demonstrated that it did not improve melanoma-specific survival (MSS). However, it continues to be performed in some scenarios. No studies have ever been published on lymph node management after a positive SLNB in the routine clinical practice in our setting. OBJECTIVES: To determine the evolution of the indication for CLND in patients with a positive SLNB, as well as the characteristics associated with its performance. MATERIAL AND METHODS: We conducted a multicenter retrospective observational study with patients with skin melanoma and positive sentinel lymph nodes diagnosed from 2017 through 2022 at 8 Spanish centers and 1 Italian center. RESULTS: A total of 430 patients were included, 54% men, with 358 (75.1%) aged between 45 and 80 years. A total of 133 cases (31%) exhibited Breslow thickness > 4mm, 206 cases (49.1%) were ulcerated, and in 213 cases (55.7%), lymph node metastasis was > 1mm. Isolated lymphadenectomy or followed by adjuvant therapy was performed in 146 patients (34.1%). After multivariate logistic regression, the factors associated with the performance of CLND were the acral lentiginous melanoma histological subtype, lymph node metastasis size > 1mm, extracapsular spread, and the participant hospital. Age > 80 years was inversely associated. CONCLUSION: While the frequency of CLND in patients with melanoma and positive SLNB has decreased, the indication for systemic adjuvant therapy in these patients has increased. However, CLND is still indicated in patients with high-risk characteristics.

Efficacy of anti-IL-23 and anti-IL-17 after adalimumab failure in psoriatic patients.

BACKGROUND: Many national guidelines at the European level recommend first-line therapy based on the anti-TNF-alpha adalimumab for treatment of psoriasis and psoriatic arthritis, mainly for economic reasons. Consequently, patients being treated with newer IL-17 and IL-23 inhibitors underwent previous unsuccessful first-line adalimumab-based therapy. OBJECTIVES: Evaluate the efficacy and safety of IL-17 and IL-23 inhibitors after treatment with adalimumab compared to adalimumab-naive psoriatic patients. METHODS: We retrospectively analysed 1053 psoriatic patients treated with anti-IL17 and anti-IL23 agents, which included 68 and 24 adalimumab-experienced and 399 and 260 bio-naive patients. Efficacy was assessed with mean PASI, PASI90, PASI100, and <3. RESULTS: Concerning the achieving of PASI100, PASI90 and PASI < 3 in patients treated with anti-IL17 agents, no significant differences were observed between adalimumab-experienced and bio-naive patients. In patients treated with an anti-IL-23 agent, a faster response was observed in bio-naive patients, with PASI < 3 significantly higher than ADA-experienced patients at 16 weeks (77% vs. 58% p = 0.048). In a sub-analysis that evaluated the performance of anti-IL17 and anti-IL23 agents in adalimumab-experienced patients with a history of secondary failure, no significant differences were found. In multivariate analysis of PASI100, only anti-IL-17 therapy appeared to have a negative impact at 52 weeks (OR: 0.54 p = 0.04) independently of previous treatment. For PASI90, type of treatment and bio-naïve status did not seem to have an impact at any time point. CONCLUSIONS: Anti-IL 23 and anti-IL 17 agents are not significantly different in terms of efficacy in bio-naive patients or as second-line therapy after failure with a biosimilar or originator adalimumab.

Topical ruxolitinib: A new treatment for vitiligo.

Vitiligo is a chronic autoimmune skin disorder whose diagnosis is often psychologically upsetting. The efficacy of the available therapies, including topical corticosteroids and topical calcineurin inhibitors, has historically been limited and the management of vitiligo is still challenging. As vitiligo is a chronic disease limited to the skin, topical rather than systemic therapies may be preferable (especially among patients with localised lesions) to avoid the long-term side-effects of the latter. A topical formulation of ruxolitinib, a selective JAK1/2 inhibitor, has recently been approved in the United States for the treatment of non-segmental vitiligo in patients aged >12 years based on data from the phase III TRuE-V1 and TRuE-V2 clinical trials. The aim of this review is to describe the current evidence concerning the efficacy and safety of topical ruxolitinib in the treatment of vitiligo, and discuss issues regarding its use in younger children and pregnant or breastfeeding women, as well as the duration and durability of treatment. The promising results obtained so far suggest that 1.5% ruxolitinib cream is an effective means of treating vitiligo.

Use of Dupilumab in 543 Adult Patients With Moderate-to-Severe Atopic Dermatitis: A Multicenter, Retrospective Study.

BACKGROUND: Dupilumab has proven to be an effective treatment for patients with moderate-to-severe atopic dermatitis (AD) in clinical trials. However, real-world experience with dupilumab in a broader population is limited. METHODS: The study population comprised adult patients with moderate-to-severe AD, defined as an Eczema Area Severity Index (EASI) score of 24 or higher, treated with dupilumab at 10 Italian teaching hospitals. We analyzed physician-reported outcome measures (EASI), patient-reported outcome measures (pruritus and sleep score, Dermatology Life Quality Index [DLQI]), and serological markers (IgE and eosinophil count) after 16 weeks. RESULTS: We enrolled 543 patients with moderate-to-severe AD. Two patients (0.4%) discontinued treatment. The median (IQR) change from baseline to 16 weeks of treatment in the EASI score was -87.5 (22.0) (P<.001). The EASI-50, EASI-75, and EASI-90 response rates were 98.1%, 81.5%, and 50.8% after 16 weeks. At 16 weeks, 93.0% of the patients had achieved a 4-point or higher improvement in DLQI from baseline. During treatment with dupilumab, 12.2% of the patients developed conjunctivitis, and total IgE decreased significantly (P<.001). Interestingly, in the multivariate logistic regression model, the risk of developing dupilumab-related conjunctivitis was associated with early onset of AD (OR, 2.25; 95%CI, 1.07-4.70; P=.03) and presence of eosinophilia (OR, 1.91; 95%CI, 1.05-3.39; P=.03). CONCLUSION: This is the broadest real-life study in AD patients treated with dupilumab to date. We observed more significant improvements induced by dupilumab in adult patients with moderate-to-severe AD than those reported in clinical trials.

Digital dermoscopy monitoring of melanocytic lesions: Two novel calculators combining static and dynamic features to identify melanoma.

BACKGROUND: Early diagnosis is the most effective intervention to improve the prognosis of cutaneous melanoma. Even though the introduction of dermoscopy has improved the diagnostic accuracy, it can still be difficult to distinguish some melanomas from benign melanocytic lesions. Digital dermoscopy monitoring can identify dynamic changes of melanocytic lesions: To date, some algorithms were proposed, but a universally accepted one is still lacking. OBJECTIVES: To identify independent predictive variables associated with the diagnosis of cutaneous melanoma and develop a multivariable dermoscopic prediction model able to discriminate benign from malignant melanocytic lesions undergoing digital dermoscopy monitoring. METHODS: We collected dermoscopic images of melanocytic lesions excised after dermoscopy monitoring and carried out static and dynamic evaluations of dermoscopic features. We built two multivariable predictive models based on logistic regression and random forest. RESULTS: We evaluated 173 lesions (65 cutaneous melanomas and 108 nevi). Forty-two melanomas were in situ, and the median thickness of invasive melanomas was 0.35 mm. The median follow-up time was 9.8 months for melanomas and 9.1 for nevi. The logistic regression and random forest models performed with AUC values of 0.87 and 0.89, respectively, were substantially higher than those of the static evaluation models (ABCD TDS score, 0.57; 7-point checklist, 0.59). Finally, we built two risk calculators, which translate the proposed models into user-friendly applications, to assist clinicians in the decision-making process. CONCLUSIONS: The present study demonstrates that the integration of dynamic and static evaluations of melanocytic lesions is a safe approach that can significantly boost the diagnostic accuracy for cutaneous melanoma. We propose two diagnostic tools that significantly increase the accuracy in discriminating melanoma from nevi during digital dermoscopy monitoring.

Primary cutaneous lymphoma patients seen at a referral dermatological centre in 1 year: A single-centre observational retrospective cohort study of the diagnoses and staging, comorbidities and associated symptoms, treatment performed and clinical course.

IMPORTANCE: Primary cutaneous lymphomas (PCL) are rare diseases, but the indolent course makes their prevalence high. Although there are many treatment options, no hierarchy is recommended. OBJECTIVE: To identify the burden of PCL and describe clinical-pathologic features; associated comorbidities; analyse treatment approaches in real-life and the parameters associated with the achievement of complete response (CR). DESIGN, SETTING AND PARTICIPANTS: In this study, all the PCL patients (384 patients) consecutively seen at the Dermatologic Clinic of the University of Turin from January 1, 2019 to December 31, 2019, with follow-up updated to December 2020, were included. MAIN OUTCOMES AND MEASURES: Subtype of PCL, demographic data, time elapsed between first lesions and diagnosis, associated symptoms, comorbidities, staging at diagnosis, high-grade transformation, blood involvement, stage progression, therapies used and response were assessed. RESULTS: 247 were cutaneous T-cell lymphomas (CTCL, 64.3%), 137 cutaneous B-cell lymphomas (CBCL, 35.7%) and the most frequent subtype was MF (48.4%). 62.3% of CTCL patients showed at least one comorbidity, mainly cardiovascular (28.7%), 20.2% show other not cutaneous neoplasms. The main approaches were skin-directed therapies (topical steroids 65.6%; phototherapy 50.2%). 39.3% patients achieved a CR during the disease course. Pruritus, the presence of comorbidities and high-grade transformation were factors associated with failure to achieve CR, whereas stage IA of MF was associated with greater achievement of CR. CONCLUSIONS AND RELEVANCE: The Th2 cytokine related development of pruritus could justify increased resistance to treatment, while the presence of associated comorbidities could reduce treatment options as well as treatment compliance.

Natural history of naevi: a two-wave study.

BACKGROUND: Naevi number changes with age. Thus, a better understanding of naevus biology will shed more light on the genetic and environmental factors involved in melanoma development. OBJECTIVES: To use a two-wave study to better understand the evolution of naevi in healthy adults. METHODS: This study is a prospective two-wave study based on adult twins from the TwinsUK registry (n = 414) who underwent total body naevus counts with an interval of at least 15 years. A negative binomial hierarchical model with two levels, the individual and the twin pair, was used to estimate expected changes in naevus count between the first and second visit, at any specific body site and on the whole body. The model was adjusted for age, calendar year at the first visit, height and skin type. RESULTS: The mean age of participants was 46 years at the first visit and 63 years at the second visit (the mean elapsed time between visits was 17 years). An increase in naevus count was observed in 235 (57%) participants and a decrease was observed in 166 (40%). The mean difference in total naevus count between the two visits was nine. The expected total body naevus count increased, on a logarithmic scale, by 0·28 [95% confidence interval (CI) 0·16-0·40] with a change in the incidence rate of total body naevus count of 32% (95% CI 17-49%). However, the observed increase in naevus count over time was observed only on the upper parts of the body, whereas there was no evidence of an increase on the lower parts. CONCLUSIONS: Naevus counts increased slightly over time at older ages, but this was dependent on body site. The overall decrease in naevus counts previously reported in cross-sectional studies has not been confirmed by this longitudinal study.

The prognostic impact of the extent of ulceration in patients with clinical stage I-II melanoma: a multicentre study of the Italian Melanoma Intergroup (IMI).

BACKGROUND: The presence of ulceration has been recognized as an adverse prognostic factor in primary cutaneous melanoma (PCM). OBJECTIVES: To investigate whether the extent of ulceration (EoU) predicts relapse-free survival (RFS) and overall survival (OS) in PCM. MATERIALS AND METHODS: We retrieved data for 477 patients with ulcerated PCM from databases of the Italian Melanoma Intergroup. Univariate and multivariable Cox proportional hazard models were used to assess the independent prognostic impact of EoU. RESULTS: A significant interaction emerged between Breslow thickness (BT) and EoU, considering both RFS (P < 0·0001) and OS (P = 0·0006). At multivariable analysis, a significant negative impact of EoU on RFS [hazard ratio (HR) (1-mm increase) 1·26, 95% confidence interval (CI) 1·08-1·48, P = 0·0047] and OS [HR (1-mm increase) 1·25, 95% CI 1·05-1·48, P = 0·0120] was found in patients with BT ≤ 2 mm, after adjusting for BT, age, tumour-infiltrating lymphocytes, sentinel lymph node status and mitotic rate. No impact of EoU was found in patients with 2·01-4 mm and > 4 mm BT. CONCLUSIONS: This study demonstrates that EoU has an independent prognostic impact in PCM and should be recorded as a required element in pathology reports.

Treatment of early-stage mycosis fungoides: results from the PROspective Cutaneous Lymphoma International Prognostic Index (PROCLIPI) study.

BACKGROUND: The PROspective Cutaneous Lymphoma International Prognostic Index (PROCLIPI) study is a prospective analysis of an international database. Here we examine front-line treatments and quality of life (QoL) in patients with newly diagnosed mycosis fungoides (MF). OBJECTIVES: To identify (i) differences in first-line approaches according to tumour-nodes-metastasis-blood (TNMB) staging; (ii) parameters related to a first-line systemic approach and (iii) response rates and QoL measures. METHODS: In total, 395 newly diagnosed patients with early-stage MF (stage IA-IIA) were recruited from 41 centres in 17 countries between 1 January 2015 and 31 December 2018 following central clinicopathological review. RESULTS: The most common first-line therapy was skin-directed therapy (SDT) (322 cases, 81·5%), while a smaller percentage (44 cases, 11·1%) received systemic therapy. Expectant observation was used in 7·3%. In univariate analysis, the use of systemic therapy was significantly associated with higher clinical stage (IA, 6%; IB, 14%; IIA, 20%; IA-IB vs. IIA, P < 0·001), presence of plaques (T1a/T2a, 5%; T1b/T2b, 17%; P < 0·001), higher modified Severity Weighted Assessment Tool (> 10, 15%; ≤ 10, 7%; P = 0·01) and folliculotropic MF (FMF) (24% vs. 12%, P = 0·001). Multivariate analysis demonstrated significant associations with the presence of plaques (T1b/T2b vs. T1a/T2a, odds ratio 3·07) and FMF (odds ratio 2·83). The overall response rate (ORR) to first-line SDT was 73%, while the ORR to first-line systemic treatments was lower (57%) (P = 0·027). Health-related QoL improved significantly both in patients with responsive disease and in those with stable disease. CONCLUSIONS: Disease characteristics such as presence of plaques and FMF influence physician treatment choices, and SDT was superior to systemic therapy even in patients with such disease characteristics. Consequently, future treatment guidelines for early-stage MF need to address these issues.

Basal cell carcinoma characterization using fusion ex vivo confocal microscopy: a promising change in conventional skin histopathology.

BACKGROUND: Ex vivo confocal microscopy (CM) works under two modes, fluorescence and reflectance, allowing the visualization of different structures. Fluorescence CM (FCM) requires a contrast agent and has been used for the analysis of basal cell carcinomas (BCCs) during Mohs surgery. Conversely, reflectance CM (RCM) is mostly used for in vivo diagnosis of equivocal skin tumours. Recently, a new, faster ex vivo confocal microscope has been developed which simultaneously uses both lasers (fusion mode). OBJECTIVES: To describe the BCC features identified on reflectance, fluorescence and fusion modes using this novel device. To determine the best mode to identify characteristic BCC features. To develop a new staining protocol to improve the visualization of BCC under the different modes. METHODS: From September 2016 to June 2017, we prospectively included consecutive BCCs which were excised using Mohs surgery in our department. The lesions were evaluated using ex vivo CM after routine Mohs surgery. The specimens were first stained with acridine orange and then stained using both acetic acid and acridine orange. RESULTS: We included 78 BCCs (35 infiltrative, 25 nodular, 12 micronodular, 6 superficial). Most features were better visualized with the fusion mode using the double staining. We also identified new CM ex vivo features, dendritic and plump cells, which have not been reported previously. CONCLUSIONS: Our results suggest that nuclei characteristics are better visualized in FCM but cytoplasm and surrounding stroma are better visualized in RCM. Thus, the simultaneous evaluation of reflectance and fluorescence seems to be beneficial due to its complementary effect. What's already known about this topic? Ex vivo fluorescent confocal microscopy (FCM) is an imaging technique that allows histopathological analysis of fresh tissue. FCM is faster - at least one-third of the time - than conventional methods. FCM has a sensitivity of 88% and a specificity of 99% in detecting basal cell carcinomas (BCCs). What does this study add? Reflectance and fluorescence modes can be used simultaneously in a new ex vivo CM device. Each mode complements the other, resulting in an increase in the detection of BCC features in fusion mode. A combined staining using acetic acid and acridine orange enhances the visualization of tumour and stroma without damaging the tissue for further histopathological analysis.

Monthly changes in serum levels of S100B protein as a predictor of metastasis development in high-risk melanoma patients.

BACKGROUND: The role of S100B protein in detecting early melanoma relapses is controversial, since most metastasis occur within normal values of S100B. OBJECTIVE: The aim of this study was to assess the performance of S100B in detecting early disease progression in high-risk melanoma patients. METHODS: Retrospective cohort study including patients with an initial diagnosis of stage IIB, IIC and III melanoma between January 2003 and July 2013. All patients were followed up in accordance with an intensive protocol based on imaging studies and serum S100B levels every 3-6 months. We compared two methods to evaluate changes in S100B. The classic method referring to a single determination of S100B above the cut-off level at the time of metastasis, which was evaluated in all patients. And a new method based on monthly changes of S100, which was used in the setting of patients with S100B levels within the normal range. RESULTS: Overall, 289 of patients were followed up for 44 months (IQR 17-73) and 45% developed metastases. During the study period, 129 patients relapsed of which 46 (35.7%) present elevated values of S100B at the time of relapse. The classic method had a sensitivity and specificity of S100B protein of 35.7% and 92.5%, respectively. Furthermore, for the patients that relapsed with normal values of S100B, the new method was applied and showed a sensitivity and specificity of 41.1% and 92.4%, respectively, allowing to detect additional relapses that were missing by the classic method. CONCLUSION: During follow-up of high-risk melanoma patients, rising serum S100B values within the normal range can be an important clue to disease progression.

The association between pesticide use and cutaneous melanoma: a systematic review and meta-analysis.

BACKGROUND: The incidence of cutaneous melanoma (CM), the deadliest form of skin cancer, has gradually increased in the last decades among populations of European origin. Epidemiological studies suggested that farmers and agricultural workers are at an increased risk of CM because they were exposed to pesticides. However, little is known about the relationship between pesticides and CM. OBJECTIVES: To investigate the association between exposure to pesticides and CM by systematically reviewing the literature. Secondary aim was to determine the categories of pesticides mainly involved in CM development. METHODS: A systematic review of the literature was performed up to September 2018 using MEDLINE, Embase and Web of Science. Studies assessing CM risk in licensed pesticide applicators were considered. Strict criteria were established to select independent studies and risk estimates; random effect models, taking into account heterogeneity, were applied. A pooled risk estimate for CM was calculated for the use of each type of pesticide and type of exposure. Between-study and estimate heterogeneity was assessed and publication bias investigated. RESULTS: A total of nine studies (two case-controls and seven cohorts) comprising 184 389 unique subjects were included. The summary relative risks for the categories 'herbicides - ever exposure', 'insecticides - ever exposure', 'any pesticide - ever exposure' and 'any pesticide - high exposure' resulted 1.85 [95% confidence interval (CI): 1.01, 3.36], 1.57 (95% CI: 0.58, 4.25), 1.31 (95% CI: 0.85, 2.04) and 2.17 (95% CI: 0.45, 10.36), respectively. Herbicides and insecticides had no between-study heterogeneity (I2  = 0%), while a significant heterogeneity (I2  > 50%) was detected for the high exposure to any pesticide. No indication for publication bias was found. CONCLUSIONS: Individuals exposed to herbicides are at an increased risk of CM. Future properly designed observational studies are required to confirm this finding.

The evolving field of Dermato-oncology and the role of dermatologists: Position Paper of the EADO, EADV and Task Forces, EDF, IDS, EBDV-UEMS and EORTC Cutaneous Lymphoma Task Force.

BACKGROUND: The incidence of skin cancers has been increasing steadily over the last decades. Although there have been significant breakthroughs in the management of skin cancers with the introduction of novel diagnostic tools and innovative therapies, skin cancer mortality, morbidity and costs heavily burden the society. OBJECTIVE: Members of the European Association of Dermato-Oncology, European Academy of Dermatology and Venereology, International Dermoscopy Society, European Dermatology Forum, European Board of Dermatovenereology of the European Union of Medical Specialists and EORTC Cutaneous Lymphoma Task Force have joined this effort to emphasize the fundamental role that the specialist in Dermatology-Venereology has in the diagnosis and management of different types of skin cancer. We review the role of dermatologists in the prevention, diagnosis, treatment and follow-up of patients with melanoma, non-melanoma skin cancers and cutaneous lymphomas, and discuss approaches to optimize their involvement in effectively addressing the current needs and priorities of dermato-oncology. DISCUSSION: Dermatologists play a crucial role in virtually all aspects of skin cancer management including the implementation of primary and secondary prevention, the formation of standardized pathways of care for patients, the establishment of specialized skin cancer treatment centres, the coordination of an efficient multidisciplinary team and the setting up of specific follow-up plans for patients. CONCLUSION: Skin cancers represent an important health issue for modern societies. The role of dermatologists is central to improving patient care and outcomes. In view of the emerging diagnostic methods and treatments for early and advanced skin cancer, and considering the increasingly diverse skills, knowledge and expertise needed for managing this heterogeneous group of diseases, dermato-oncology should be considered as a specific subspecialty of Dermatology-Venereology.

Improving the disease awareness: how a communication campaign brings hidradenitis suppurativa to the light.

BACKGROUND: Hidradenitis suppurativa is an inflammatory skin disease that presents a recurrence of painful and suppurating lesions in the apocrine gland-bearing regions, with a strong impact on the patients' life quality. Despite its peculiar presentation, early forms are often underestimated by patients and this would inevitably result in late diagnosis and delayed therapy. OBJECTIVES: Improved communication around the disease could facilitate self-diagnosis and a quicker response from healthcare practitioners, especially in this moment when we dispose of effective treatment against this disease. METHODS: A HS awareness campaign was conducted for 2 years with the help of a media agency and a patients' association. RESULTS: Results confirm that a better communication has a strong impact on the disease awareness. CONCLUSIONS: This paper demonstrates that the more this disease awareness is carried on, the more quick, effective and efficient the patient's management could be.

Favourable prognostic role of histological regression in stage III positive sentinel lymph node melanoma patients.

BACKGROUND: Sentinel lymph node (SLN)-positive melanoma patients are a heterogeneous group of patients with survival rates ranging from ∼20 to over 80%. No data are reported concerning the role of histological regression on survival in stage III melanoma. METHODS: The study included 365 patients with positive SLN from two distinct hospitals. The model was developed on patients from 'AOU Città della Salute e della Scienza di Torino', and externally validated on patients from IRCCS of Candiolo. Survival analyses were carried out according to the presence of regression and adjusted for all other prognostic factors. RESULTS: Among patients followed at 'AOU Città della Salute e della Scienza di Torino' (n=264), the median follow-up time to death or censoring (whatever two events occurred earlier) was 2.7 years since diagnosis (interquartile range: 1.3-5.8). In all, 79 patients died from melanoma and 11 from other causes. Histological regression (n=43) was associated with a better prognosis (sub-HR=0.34, CI 0.12-0.92), whereas the other factors above showed an inverse association. In the external validation, the concordance index was 0.97 at 1 year and decreased to 0.66 at 3 years and to 0.59 at 5 years. Adding histological regression in the prognostic model increased the discriminative ability to 0.75 at 3 years and to 0.62 at 5 years. Finally, using a cutoff of 20% for the risk of death led to a net re-classification improvement of 15 and 11% at 3 and 5 years after diagnosis, respectively. CONCLUSIONS: Histological regression could lead to an improvement in prognostic prediction in patients with stage III-positive SLN melanoma.