Age affects drug survival rates of interleukin (IL)-17 and IL-23 inhibitors in patients with plaque psoriasis: Results from a retrospective, multicentric, multi-country, cohort study.

BACKGROUND: Scarce data related to the drug survival of biologic agents in psoriasis patients aged ≥65 years is available. OBJECTIVES: To evaluate the drug survival of interleukin (IL)-23 or the IL-17 inhibitors approved for the treatment of moderate-to-severe psoriasis in elderly patients (aged ≥65 years), compared with younger adult patients (aged <65 years), and to identify clinical predictors that can influence the drug survival. METHODS: This retrospective multicentric cohort study included adult patients with moderate-to-severe psoriasis, dissecting two-patient subcohorts based on age: elderly versus younger adults. Kaplan-Meier estimator and proportional hazard Cox regression models were used for drug survival analysis. RESULTS: We included 4178 patients and 4866 treatment courses; 934 were elderly (1072 treatment courses), and 3244 were younger patients (3794 treatment courses). Drug survival, considering all causes of interruption, was higher in patients aged <65 years than in elderly patients overall (log-rank p < 0.006). This difference was significant for treatment courses involving IL-23 inhibitors (p < 0.001) but not for those with IL-17 inhibitors (p = 0.2). According to both uni- and multi-variable models, elder age was associated with an increased risk of treatment discontinuation (univariable analysis: HR: 1.229, 95% CI 1.062-1.422; p < 0.006; multivariable analysis: HR: 1.199, 95% CI 1.010-1.422; p = 0.0377). Anti-IL-23 agents were associated with a reduced likelihood of treatment discontinuation after adjusting for other variables (HR: 0.520, 95% CI 0.368-0.735; p < 0.001). Being previously treated with IL-17 inhibitors increased the probability of discontinuation. CONCLUSION: Elderly patients with psoriasis have an increased risk of biologic treatment discontinuation compared with younger adult patients, particularly, if being treated with IL-23 inhibitors. However, in stratified analyses conducted in elderly patients, IL-23 inhibitors showed higher drug survival rates than IL-17 inhibitors.

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.

Dermatitis Artefacta: A Retrospective Descriptive Study on 46 Patients.

INTRODUCTION: Self-induced dermatoses are self-inflicted skin lesions, whose occurrence patient denies responsibility for. OBJECTIVES: The aim of this study was to retrospectively investigate all the clinical records of dermatitis artefacta (DA) in order to put special focus on: a) epidemiological aspects; b) location, shape and additional features of the lesions; c) availability of psychiatric details in the records. METHODS: A retrospective observational descriptive study on 46 patients affected by dermatitis artefacta was conducted from January 2015 to March 2021. The only inclusion criterion was clinical or histological diagnosis of DA in patients for which we had clinical images. RESULTS: The most frequent type of lesions were erosions/excoriations and ulcers (14/46, 30.4% and 13/46, 28.3% respectively) followed by ecchymoses (9/46, 19.5%), vasculitis-like lesions (5/46, 10.9%), crusted plaques (3/46, 6.5%), scales (1/46, 2.2%) and erythema (1/46, 2.2%). Thirty-three percent of the medical records generically referred to the presence of psychiatric disorder, but none of them included a specific psychiatric diagnosis. CONCLUSIONS: In our study the main dermatologic lesions observed in DA were represented by excoriations and ulcers and that the shape and location of the lesions are essential for a correct diagnosis.

Effectiveness and Safety After a Switch to Tildrakizumab: A Real World Multicenter Italian Study in Psoriasis.

INTRODUCTION: Tildrakizumab is a humanized IgG1κ monoclonal antibody targeting the p19 subunit of interleukin (IL)-23, approved in 2018 for the treatment of patients with moderate-to-severe chronic plaque psoriasis. OBJECTIVES: This study aimed to evaluate the effectiveness, safety and survival of tildrakizumab in the medium term (48 weeks) in psoriatic patients failure to previous biologic treatment in a real world setting. METHODS: This was a retrospective, multicenter observational study that included adult patients with moderate-to-severe plaque psoriasis, failure to previous biologic therapy, consecutively treated with tildrakizumab. Psoriasis Area Severity Index (PASI) and Body Surface Area (BSA) values were recorded at baseline, at 12 and 48 weeks of treatment. Safety and tolerability of tildrakizumab were investigated by examining the presence of any adverse events. RESULTS: Overall 51 patients were enrolled. Baseline disease severity was moderate to severe with a mean PASI score of 19.2 ± 8.5, mean BSA of 16 ± 10.4, and mean Dermatology Life Quality Index (DLQI) of 18.2 ± 6.8. A significant reduction in the mean PASI score was detected at 12 weeks of tildrakizumab therapy (3.5 ± 2.7, P < 0.001), with a further improvement at week 48 (0.6 ± 1.5, P < 0.001). At week 12, there was a great improvement in BSA score for all groups (P <0.001) with further increase at week 48. The effectiveness was confirmed also by DLQI assessment, with a significant decrease at week 12 and even more at week 48 (P <0.001). CONCLUSIONS: This study confirms the effectiveness of tildrakizumab in daily clinical practice in patients with moderate-to-severe plaque psoriasis.

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.

New Perspectives in the Management of Chronic Hand Eczema: Lessons from Pathogenesis.

Chronic hand eczema (CHE) is a common inflammatory skin condition that significantly impacts the quality of life. From work-related disabilities to social embarrassment, pain, and financial costs, the burden on society is substantial. Managing this condition presents challenges such as long-term treatment, poor patient compliance, therapy side effects, and economic feasibility. As a result, significant efforts have been made in this field in recent years. Specifically, the broader understanding of CHE pathogenesis has led to the development of new drugs, both topical and systemic. The aim of this narrative review is to summarize the current available data on hand eczema pathophysiology and explore the resulting developments in drugs for its treatment. A comprehensive search on PubMed and the other main scientific databases was conducted using keywords related to CHE and its pathogenesis. The most relevant pathways targeted by therapies include the JAK-STAT cascade, IL-4, and IL-13 axis, phosphodiesterase 4 enzyme, and chemo-attractant cytokines. In the near future, physicians will have a plethora of therapeutic alternatives. Consequently, they should be well-trained not only in how to use these alternatives but also how to combine these treatments to address the ongoing challenges related to efficacy, tolerability, and safety.

Evaluation of the Role of Faecal Calprotectin in the Management of Psoriatic Patients under Treatment with Biologic Drugs.

Background: Fecal calprotectin has emerged as a significant, validated, and non-invasive biomarker allowing for the evaluation of inflammatory bowel disease. Our study assessed the reliability of the use of faecal calprotectin as a valuable tool in the management of psoriatic patients on biological therapy. Methods: This was a single-centre prospective study including adult patients affected by moderate-to-severe psoriasis starting biological therapy. Faecal calprotectin levels were evaluated at baseline and at week 24 (W24) of treatment in all enrolled patients. Results: Overall, 129 patients were enrolled. The mean baseline faecal calprotectin levels were 74.7 µg/g and a significant reduction was detected at W24 of biological therapy (57.5 µg/g). An analysis of faecal CP values stratified by therapy type was performed. No significant reduction was assessed at W24 for any of the anti-IL17 drugs, whereas a significant reduction was detected for all IL23 inhibitors. Conclusions: Our study showed the potential use of faecal CP levels as a valuable tool for exploring intestinal inflammation in the management of psoriatic patients undergoing treatment with biologic drugs.

Dupilumab Treatment in Children Aged 6-11 Years With Atopic Dermatitis: A Multicentre, Real-Life Study.

BACKGROUND: The management of paediatric atopic dermatitis (AD) is challenging, mostly relying on emollients and topical corticosteroids. Dupilumab, a fully human monoclonal antibody, has been recently approved for the treatment of children aged 6-11 years with moderate-to-severe AD not adequately controlled with topical therapies or when those therapies are not advisable. OBJECTIVES: The aim of this study was to evaluate in real life the effectiveness and safety of dupilumab in the treatment of children aged from 6 to 11 years. METHODS: Demographic and clinical data of children aged 6-11 years, affected by moderate-to-severe AD and treated with dupilumab, were retrospectively collected from 24 dermatological and paediatric referral centres. Dupilumab was administered subcutaneously at an induction dose of 300 mg on day (D) 1, followed by 300 mg on D15 and 300 mg every 4 weeks. Disease severity was assessed at baseline and after week 2 (W2), W4 and W16 of dupilumab therapy using Eczema Area Severity Index (EASI), Pruritus Numerical Rating Scale (P-NRS) and Sleep NRS (S-NRS) and Children's Dermatology Life Quality Index (c-DLQI) score. RESULTS: A total of 55 AD children (24 males [43.64%], 31 females [56.36%]; mean age 9.35 ± 1.75 years) were included. A significant improvement in EASI score, P-NRS, S-NRS and c-DLQI was observed from baseline to W16 of treatment with dupilumab. In particular, at W16 the proportion of patients achieving EASI75 was 74.54%. Moreover, at the same timepoint a significant mean percentage reduction for P-NRS, S-NRS and c-DLQI was also observed (68.39%, 70.22% and 79.03%, respectively). CONCLUSIONS: Our real-life data seem to confirm the effectiveness of dupilumab in paediatric patients on all disease aspects, including extent and severity of signs, intensity of symptoms, sleep and QoL, with a good safety profile.

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.