Real-Life Effectiveness and Safety of Guselkumab in Patients with Psoriasis Who Have an Inadequate Response to Ustekinumab: A 3-Year Multicenter Study.

Background: Guselkumab is the first approved human IgG1λ monoclonal antibody selectively targeting the p19 subunit of IL23. Its effectiveness and safety were widely reported by clinical trials. However, these results must be confirmed in real life since its safety deals with more complicated subjects with respect to trials. Currently, real-life data on the use of guselkumab following treatment failure with ustekinumab are limited, and existing studies usually show a small cohort and/or a reduced follow-up period. In this context, the aim of our study was to evaluate the use of guselkumab in patients who previously did not respond to ustekinumab after up to 3 years of treatment. Methods: A multicenter retrospective study was performed. The study enrolled patients affected by moderate-to-severe plaque psoriasis undergoing treatment with guselkumab who were attending the Psoriasis Center of nine different centers in the Campania region of Italy. Demographic and clinical features were collected for each patient at baseline. Moreover, data on psoriasis severity and adverse events (AEs) were collected at each follow-up visit (week (W)16-W36-W52-W104-W156). Results: A total of 112 patients (70 male, 62.5%; mean age 54.8 ± 11.7 years old) were enrolled. Of these, 48 (42.9%), 34 (30.4%), and 16 (14.3%) reached 1, 2, and 3 years, respectively, of follow-up under guselkumab. A statistically significant clinical improvement was observed since W16, and sustained effectiveness was reported at each timepoint up to W156. No serious AEs were collected. Moreover, a sub analysis on the body mass index, involvement of difficult-to-treat areas, and presence of psoriatic arthritis (PsA) showed that the presence of PsA or palmoplantar psoriasis was associated with a reduced clinical improvement at W16 and W36, without differences from W52. In contrast, the efficacy of guselkumab does not seem to be affected by the BMI, involvement of fingernails, or location in the genital or scalp area. Conclusions: To sum up, our long-term real-life multicenter retrospective study confirmed the efficacy and safety of guselkumab following ustekinumab discontinuation up to 156 weeks of treatment.

Melanoma in children: A systematic review and individual patient meta-analysis.

The current evidence on paediatric melanoma is heterogeneous, especially regarding the prognosis of different histological subtypes. We sought to systematically review the evidence on paediatric melanoma, highlighting the major sources of heterogeneity and focusing on available data on single patients. A systematic search was performed from 1948 to 25 January 2021. Only studies reporting at least one case of cutaneous melanoma in patients aged ≤18 years were included. Unknown primary and uncertain malignant melanomas were excluded. Three couples of authors independently performed title/abstract screening and two different authors reviewed all the relevant full texts. The selected articles were manually cross-checked for overlapping data for qualitative synthesis. Subsequently data on single patients were extracted to perform a patient-level meta-analysis. PROSPERO registration number: CRD42021233248. The main outcomes were melanoma-specific survival (MSS) and progression-free survival (PFS) outcomes. Separate analyses were done of cases with complete information on histologic subtype, focusing on superficial spreading (SSM), nodular (NM) and spitzoid melanomas, as well as of those classified as de-novo (DNM) and acquired or congenital nevus-associated melanomas (NAM). The qualitative synthesis covered 266 studies; however, data on single patients were available from 213 studies including 1002 patients. Among histologic subtypes, NM had a lower MSS than both SSM and spitzoid melanoma, and a lower PFS than SSM. Spitzoid melanoma had a significantly higher progression risk than SSM and trended toward lower mortality. Focusing on nevus-associated status, DNM demonstrated better MSS after progression than congenital NAM, and no differences were highlighted in PFS. Our findings describe the existence of different biological patterns in paediatric melanoma. Specifically, spitzoid melanomas demonstrated intermediate behaviour between SSM and NM and showed a high risk of nodal progression but low mortality. This raises the question of whether spitzoid lesions are being over-diagnosed as melanoma in childhood.

Real-World Experience With Topical 5-Fluorouracil 4% (40 mg/g) Cream for the Treatment of Actinic Keratosis.

INTRODUCTION: 5-fluorouracil (5-FU) is one of the most effective topical treatments for actinic keratosis (AK). A new 4% formulation of 5-FU was recently approved in Europe. OBJECTIVES: This study aimed at evaluating 4% 5-FU cream safety and effectiveness in a real-world setting. METHODS: Adult AK patients were retrospectively selected from the University of Campania Dermatology Unit database. Selection criteria included a diagnosis of non-hyperkeratotic, non-hypertrophic AK (Olsen grade I and II) of the face, ears, and/or scalp, treatment with 4% 5-FU once daily for 4 weeks, and at least 3 follow-up visits (4 and 8 weeks after treatment initiation, and 6 months after treatment end). The primary objectives were to evaluate AK lesions improvement at 8 weeks and relapse rate at 6 months. Patient-reported erythema and burning sensation intensity were also assessed at 4 weeks. RESULTS: Ninety-eight patients were included in this analysis (male/female 80/18, mean age 74.7 years). AK lesions improvement at 8 weeks resulted complete or significant in 74.5% and 20.4% of the patients, respectively. At 6 months, 65.3% of the patients did not show AK relapses. Burning sensation at 4 weeks was reported as light, moderate, or absent by 44.9%, 22.4%, and 31.6% of the patients, respectively. Erythema was reported as light, moderate, or absent by 37.8%, 51%, and 10% of the patients, respectively. Burning sensation and erythema disappeared gradually during follow-up. No other side effects were reported. CONCLUSIONS: In this real-world study 4% 5-FU proved to be highly effective for AK lesions clearance with a favorable safety profile.

The current clinical approach to difficult-to-treat basal cell carcinomas.

INTRODUCTION: Basal cell carcinoma (BCC) is the most common malignant tumor in adult white populations. If BCCs are not treated for years, if they cause massive destruction of the surrounding tissues, if they are considered unresectable or not eligible for radiotherapy they become progressively 'locally advanced' (laBCC) or metastatic (mBCC). These tumors are defined as 'difficult-to-treat BCC.' AREAS COVERED: A comprehensive search on PubMed was conducted to identify relevant literature about the several approved and recommended treatment options for the management of difficult-to-treat BCC published from January 2012 to July 2022. Surgical options, radiotherapy, hedgehog inhibitors, immunotherapy, and combined treatments are discussed. The keywords used were basal cell carcinoma; difficult-to-treat BCC; management of difficult-to-treat BCC; surgical therapy; radiotherapy; hedgehog inhibitors; immunotherapy. EXPERT OPINION: Identifying the best approach to DTT BCCs is one of the main challenges for the dermato-oncologist. The introduction of HHI for the treatment of advanced BCCs has revolutionized the clinical management of DTT BCCs. The immune checkpoint inhibitor cemiplimab has been approved for the treatment of locally advanced or metastatic BCC refractory to HHI therapy or in patients intolerant to HHI therapy. Multidisciplinary teams (MDTs) play a key role in managing these complex patients.

Reflectance confocal microscopy in paediatric patients: Applications and limits.

Reflectance confocal microscopy (RCM) is a non-invasive diagnostic tool extensively studied for adult patients. In this retrospective case series conducted at the Dermatology Unit of the University of Campania, Naples, Italy, all patients under 19 years old who were submitted to RCM from January 2011 to December 2021 where evaluated. The aim of the study was to review the most usual indications and possible benefits that it might add for children. Data collection included 215 patients (86 males and 129 females, mean age: 12). Most of the exams (n = 85; 39.5%) were performed for lesions clinically compatible with Spitz nevi, congenital nevi (n = 50 23,2%) and atypical melanocytic lesions (n = 46; 21%) among which two melanomas were detected. RCM can be an useful instrument when evaluating paediatric patients and may help avoid unnecessary biopsy in most cases, representing an additional instrument to improve diagnostic accuracy.

Poikiloderma With Neutropenia and Mastocytosis: A Case Report and a Review of Dermatological Signs.

Poikiloderma with neutropenia (PN) is a very rare genetic disorder mainly characterized by poikiloderma and congenital neutropenia, which explains the recurrence of respiratory infections and risk of developing bronchiectasis. Patients are also prone to develop hematological and skin cancers. Here, we present the case of a patient, the only child of apparently unrelated Serbian parents, affected by PN resulting from the homozygous mutation NM_024598.3:c.243G>A (p.Trp81Ter) of USB1; early onset of poikiloderma (1 year of age) was associated with cutaneous mastocytosis. We also provide a review of the literature on this uncommon condition with a focus on dermatological findings.

Are we born and do we die without nevi? A cross-sectional study.

BACKGROUND: It is well known that the number of nevi varies with age. However, there are a few data in the literature concerning total nevus count at different ages. The aim of this study was to assess and compare the total nevus count among different age groups. METHODS: The total nevus count was assessed in consecutive patients belonging to nine age groups. Median nevus count was calculated and compared for each age group. Multivariate logistic regression analysis was used to define the influence of sex and phototype on the association between nevus count and age. RESULTS: We enrolled 900 patients (461, 51.2% females), with a median age of 46 years and a total of 18,136 nevi. Significant differences were found in the median total nevus count among all age groups (P < 0.001), with a significant increase in the first two decades and a significant decrease after the age of 50 years. A similar trend was also observed in subgroups. The differences observed in the total body nevus count among age groups were independent of sex and phototype. CONCLUSIONS: We demonstrate that the total nevus count significantly increases during childhood and gradually decreases in the elderly.

Nevocentric erythema multiforme in a child.

A 9-year-old girl presented with multiple, ring-shaped, erythematous, nonscaly plaques on the trunk, face and arms, most surrounding preexisting melanocytic nevi. She had experienced recurring episodes of herpes simplex labialis over several years (average 4/year), the last occurring 10 days prior.

Italian expert consensus paper on the management of patients with actinic keratoses.

Two round tables involving experts were organized in order to reach a consensus on the management of patients with actinic keratosis (AK). In the first, seven clinical questions were selected and analyzed by a systematic literature review, using a Population, Intervention, Control, and Outcomes framework; in the second, the experts discussed relevant evidences and a consensus statement for each question was developed. Consensus was reached among experts on how to best treat AK patients with respect to different clinical scenarios and special populations. Lesion-directed treatments are preferred in patients with few AKs. Patients with multiple AKs are challenging, with more than one treatment usually needed to achieve complete lesion clearance or a high lesion response rate, therapy should be personalized, based on previous treatments, patient, and lesion characteristics. Methyl aminolevulinate-PDT, DL (day light) PDT, and imiquimod cream were demonstrated to have the lowest percentage of new AKs after post treatment follow-up. For IMQ 5% and 3.75%, a higher intensity of skin reactions is associated with higher efficacy. Photodynamic therapy (PDT) is the most studied treatment for AKs on the arms. Regular sunscreen use helps preventing new AKs. Oral nicotinamide 500 mg twice daily, systemic retinoids and regular sunscreen use were demonstrated to reduce the number of new squamous cell carcinomas in patients with AKs. Limited evidence is available for the treatment of AKs in organ transplant recipients. There is no evidence in favor or against the use of any of the available treatments in patients suffering from hematological cancer.

Plasma radiofrequency ablation for treatment of benign skin lesions: Clinical and reflectance confocal microscopy outcomes.

BACKGROUND: In the latest few years, plasma radiofrequency ablation has turned out a good option for treatment of several benign skin lesions. The technique can be easily performed to treat skin lesions with limited tissue invasion and no residual scars or hypo/hyperpigmentation areas. OBJECTIVE: The aim of this study was to assess the effects of plasma radiofrequency ablation in treatment of benign skin lesions, through clinical and reflectance confocal microscopy outcomes. METHODS: Six patients who presented benign skin lesions underwent long-wave plasma radiofrequency ablation treatment with DAS medical device (Technolux, Italia). Reflectance confocal microscopy analysis was performed at baseline and after 1 month. RESULTS: The treatment was well tolerated; only a slight erythema and a thin crust on the treated area were referred for 3-7 days after treatment. After one month from treatments, we observed the complete disappearance of the lesions and no significant signs of inflammation, redness, hypo/hyperpigmentation, or scars on the site of the treated areas; these clinical data were also confirmed by reflectance confocal microscopy analysis. CONCLUSIONS: Long-wave plasma radiofrequency ablation actually can be considered a well-tolerated, painless, safe, effective, and low-cost procedure for skin treatments.