ABSTRACT
In the last decade, dupilumab, a monoclonal human antibody inhibiting IL-4/IL-13 signaling, has revolutionized the therapeutic management of moderate-to-severe atopic dermatitis (AD), permitting a long-term control of its signs and symptoms. The aim of this study was to identify histologic predictors of dupilumab efficacy after 16 weeks of treatment in a cohort of forty adult patients with moderate to severe AD who had undergone a skin biopsy for diagnostic purposes prior to treatment initiation. We found that EASI 75 and EASI 90 responses at week 16 were significantly associated with perivascular localization (OR=17.6, p=0.038) and lichenoid distribution (OR=31.8, p=0.025) of the immune infiltrate. Moreover, for each unit increase in the number (cells/m2) of CD4+ cells, the likelihood to achieve EASI75 response decreased by 1% (OR=0.99, p=0.037). In conclusion our study suggested a few pre-treatments qualitative and quantitative immunohistochemical features as promising markers predicting dupilumab response in AD patients.
ABSTRACT
Background: Psoriatic disease, a chronic immune-mediated systemic inflammatory condition, significantly impairs patients' quality of life. The advent of highly targeted biological therapies has transformed treatment strategies, emphasizing the importance of selecting the most effective and cost-efficient option. Secukinumab, an IL-17A inhibitor, has demonstrated efficacy and safety in treating moderate-to-severe plaque psoriasis (PsO). However, long-term real-world data on its effectiveness and persistence rate are limited. Methods: This retrospective study, conducted across eight Italian dermatology centers, aimed to evaluate the 6-year persistence rate and effectiveness of secukinumab in patients with PsO. Additionally, the study investigated the onset of psoriatic arthritis during treatment. Results: Overall, 166 adult patients were analyzed. Their median age was 53.9 years. The mean BMI was 26.5. Of the 166 patients, 64 were bio-experienced while 102 were bio-naïve. A progressive reduction in PsO severity measured by PASI scores over 6 years of treatment was revealed: the PASI score decreased from a baseline value of 18.1 (±9.1) to 0.7 (±1.6) after 6 years of follow-up. Adverse events, including mucocutaneous fungal infections and cardiovascular disturbances, were reported in 19.9% of patients. The persistence rate was 86.8% at 24 months, decreasing to 66.4% at 72 months. Psoriatic arthritis onset during treatment was observed in 15 (9.0%) of patients. Conclusions: This study highlights the sustained effectiveness and favorable safety profile of secukinumab over 6 years, providing valuable real-world evidence. Understanding the long-term persistence rate and predictors of discontinuation could help clinicians optimize treatment decisions and improve patient outcomes in PsO management. We found that the absence of scalp PsO, no involvement of the genital area and normal weight were the best factors of persistence in secukinumab treatment in the long term.
ABSTRACT
INTRODUCTION: Night shift work disrupts circadian rhythms and has been associated with immune system alterations and various health conditions. However, there is limited data regarding its impact on psoriasis. The aim of our study was to compare psoriasis severity and the hormonal and immunological profile in patients with a night shift work to those with a daytime occupation. METHODS: In this case-control study, we enrolled psoriatic patients aged >18 years engaged in night shift work and a control group of psoriatic patients with a daytime occupation. A further categorization was performed by the duration of night shift work: < or ≥7 days a month and < or ≥8 years. Disease severity was evaluated by PASI, BSA, and DLQI, and blood samples were taken to measure various hormonal and immunological markers. Univariable and multivariable analysis were performed to assess differences between the two groups. RESULTS: A total of 40 night shift workers were included, along with 36 patients in the control group. Patients who worked night shifts at least 7 days a month had significantly higher PASI scores (11.2 ± 6.6 vs. 8.5 ± 6.6; p = 0.04) and higher IL-8 serum (115.33 ± 463.65 pg/mL vs. 19.98 ± 29.78 pg/mL; p = 0.006) compared to patients who did not. Night shifts workers for at least 8 years had higher BMI (28.65 ± 4.56 vs. 25.32 ± 5.50, p = 0.010), and females had higher testosterone levels (0.46 ± 0.53 ng/mL vs. 0.23 ± 0.13 ng/mL; p = 0.055). CONCLUSION: Night shift might increase psoriasis severity and have an impact on chronic inflammation, obesity, and hormonal imbalances.
Subject(s)
Psoriasis , Severity of Illness Index , Shift Work Schedule , Humans , Psoriasis/blood , Psoriasis/immunology , Psoriasis/physiopathology , Case-Control Studies , Female , Male , Adult , Shift Work Schedule/adverse effects , Middle Aged , Circadian Rhythm , Interleukin-8/blood , Testosterone/bloodABSTRACT
INTRODUCTION: Pigmentation of lip and/or genitalia is mainly due to the development of benign melanotic macules, with a less occurrence of melanocytic and other non-melanocytic lesions. Mucosal melanoma has worse prognosis compared with cutaneous counterpart, hence identification of atypical features for an early diagnosis is crucial. OBJECTIVES: The aim of this study was to report further data of confocal features characterizing pigmented mucosal lesions of genital area and of the lips and test the diagnostic role of the reflectance confocal microscopy (RCM)lip score. METHODS: Clinical, dermoscopic and RCM images of histologically proven pigmented lesions, involving the genital area (vulva or glans penis) and lip, were retrospectively reviewed. RCM images were evaluated for malignant criteria, and statistical analysis was conducted for categorical variables. RESULTS: Seventy pigmented lesions were included in the study and divided into two groups based on the body area location: lip (17) and genital area (53). Architectural disarray (P = 0.002), dendritic (P = 0.031) and roundish cells in epidermis (P < 0.0001), interpapillary dendritic cells (P = 0.039) and junctional atypical cells (P = 0.002) were associated to genital melanoma. Melanoma involving the lip was characterized by roundish cells in epidermis, a criterion found in one labial benign lesion, only (P = 0.005). Main limitations of the study are the inclusion of low melanomas and the presence of epidermal dendritic cells in melanosis and melanoma, as a confusing factor in imaging. CONCLUSIONS: Dermatologists should consider confocal microscopy as an adjunctive tool to dermoscopy in the differential diagnosis of pigmented mucosal lesions, especially in presence of clinical and dermoscopic findings suspicious for malignancy.
ABSTRACT
Papulopustular rash (PPR) is the most frequent cutaneous adverse event during treatment with epidermal growth factor receptor inhibitors (EGFRis). Although often mild in severity, it can impair patients' quality of life and may also be a reason for discontinuing or changing the dose of the antineoplastic treatment. During COVID-19 pandemics, the use of surgical masks drastically increased and it had an impact on the face skin microenvironment, favoring the worsening of dermatological pathologies. We reported the relapse of PPR in patients treated with EGFR inhibitors who consistently wore face masks (>6 hours/day). All the patients developed the PPR within 6 months of starting mask use. Compared to the PPR occurred previously, after mask use, the skin eruption was more severe and affected mainly those regions of the face which came into contact with the mask. Patients received topical or systemic treatment, obtaining complete response in 65.7% of the cases. The establishment of an early treatment for the PPR allows continuing the oncologic treatment, without any suspension which could result in a decreased oncologic outcome. In conclusion, when using these devices, it is recommended to use special precautions, particularly in oncologic patients, by using a daily prophylactic skincare and replacing masks regularly with regular and frequent breaks.
ABSTRACT
Hidradenitis suppurativa (HS) is a chronic-relapsing inflammatory skin disease. It usually appears in the second and third decades, but a smaller proportion of patients develop late-onset HS. Geriatric HS, defined as the persistence or the development of HS after the age of 65 years, has been poorly explored. This study aimed to investigate the clinical features, treatment management and response to therapies of HS elderly subjects (≥65 years old). We designed a multicentric observational study, gathering data from seven Italian university hospitals. Demographic and clinical data of HS patients aged over 65 years were collected at baseline, week 12 and week 24. Overall, 57 elderly subjects suffering from HS were enrolled. At baseline, disease severity was predominantly moderate-to-severe, with 45.6% of patients classified as Hurley III. The gluteal phenotype was the most frequently observed; it also appeared to affect patients' quality of life more than other phenotypes. Gluteal involvement was detected in about half (49.1%) of cases and associated with severe stages of the disease. In terms of therapeutic response, Hurley III patients showed the persistency of higher values of mean IHS4, DLQI, itch- and pain-NRS scores compared to Hurley I/II. In conclusion, disease severity in this subpopulation appears high and treatment is often challenging.
ABSTRACT
Despite the introduction of targeted (BRAFi/MEKi) and immune checkpoint inhibitors (ICIs) has significantly reduced the recurrence rate and improved the overall survival (OS) of patients with Stage III and IV melanoma, only a percentage will benefit of durable disease control. The aim of this study was to examine whether the levels of circulating tumour DNA (ctDNA) in plasma of advanced melanoma patients undergoing BRAFi/MEKi or ICIs vary according to the patients' survival outcomes (i.e. progression-free survival (PFS) and OS) and disease progression. Plasma samples of Stage III-IV melanoma patients were collected at baseline (treatment initiation) and thereafter every 3 months. Circulating BRAFV600E/K and NRASQ61R/K mutations were analysed through droplet digital PCR (ddPCR, Bio-Rad) in a total of 177 plasma samples from 48 melanoma patients (19 Stage III, 29 Stage IV). Baseline ctDNA concentration was significantly associated with OS (HR = 1.003, 95% CI = 1.000-1.006, p = 0.043) and PFS (HR = 1.004, 95% CI = 1.000-1.007, p = 0.029) independent of clinical-prognostic confounders. For each unit increase in the ∆ctDNA (concentration difference between the last follow-up and baseline) there was a 24% increased risk of disease progression, irrespective of treatment type and stage at diagnosis (OR = 1.24, 95% CI = 1.03-1.49, p = 0.020, AUC = 0.93). Patients with reduction of ctDNA level from baseline to the last follow-up had longer OS (HR = 0.14; 95% CI = 0.05-0.44, p = 0.001) and PFS (HR = 0.08; 95% CI = 0.03-0.27, p < 0.0001) compared to patients with increased ctDNA, including adjustment for confounding factors. Our findings suggest that variation of ctDNA over time during melanoma treatment reflects the clinical outcome and tumour response to therapy and might be helpful in clinical monitoring.
ABSTRACT
OBJECTIVES: The purpose of this study was to analyze the drug survival rate of dupilumab up to 2 years in a large real-world cohort of adult patients affected by moderate/severe atopic dermatitis (AD), and to investigate the clinical, demographic and predictive factors influencing the patients' treatment persistence. MATERIAL AND METHODS: This study included adult patients affected by moderate-to-severe AD treated with dupilumab for at least 16 weeks who visited 7 dermatologic outpatient clinics in Lazio, Italy, from January 2019 until August 2021. RESULTS: A total of 659 adult patients (345 male [52.3%], mean age: 42.8 years) with an average treatment duration of 23.3 months were enrolled in the study. Overall, 88.6% and 76.1% of patients were still on treatment after 12 and 24 months, respectively. The drug survival rate for discontinuation due to AEs and dupilumab ineffectiveness was 95.0% at 12 months and 90.0% at 24 months. The main reasons for drug discontinuation included inefficacy (29.6%), failed compliance (17.4%), persistent efficacy (20.4%) and adverse events (7.8%). Adult AD onset (≥18 years) and EASI score severity measured at the last follow-up visit were the only factors significantly associated with lower drug survival. CONCLUSION: This study revealed an increased cumulative probability of dupilumab survival at 2 years, reflected by a sustained effectiveness and a favorable safety profile of the drug.
Subject(s)
Dermatitis, Atopic , Humans , Adult , Male , Dermatitis, Atopic/drug therapy , Treatment Outcome , Severity of Illness Index , Antibodies, Monoclonal, Humanized/adverse effects , Double-Blind MethodABSTRACT
BACKGROUND: Dupilumab is a monoclonal antibody against the IL-4/IL-13 receptor-subunit approved for the treatment of moderate-severe atopic dermatitis (AD). Some attempts to increase dose interval have been described in both trial and real-world settings. OBJECTIVE: This study aimed to identify predictive clinical and demographic factors affecting patient selection for dose spacing or treatment withdrawal due to satisfactory response. MATERIALS AND METHODS: This retrospective study included adult patients with moderate-to-severe AD treated with dupilumab for at least 16 weeks. Descriptive statistics were performed to analyze demographic and clinical variables. Logistic regression models were used to identify predictor variables. RESULTS: A total of 818 adult patients with moderate-to-severe AD was included in the study and 12% (97/818) of them performed dose spacing to 3-4 weeks or treatment withdrawal (8%, 67/818). The presence of non-cutaneous atopic manifestations (OR = 1.59, 95%CI = 1.06-2.38, p = 0.024), prurigo nodularis phenotype (OR = 4.5, 95%CI = 1.87-10.9, p = 0.001) and the age at treatment initiation (OR = 1.82, 95%CI = 1.12-2.94, p = 0.015) were confirmed as the strongest predictors of dose spacing or treatment withdrawal while maintaining dupilumab effectiveness. CONCLUSION: Our findings contribute to define the patient profile that could maintain the therapeutic response after dose spacing or treatment withdrawal.
Predicting factors identified patients with dupilumab who could benefit of dose spacing or treatment withdrawal.
Subject(s)
Dermatitis, Atopic , Humans , Dermatitis, Atopic/drug therapy , Retrospective Studies , Treatment Outcome , Severity of Illness Index , Interleukin-4 Receptor alpha SubunitABSTRACT
Introduction: Pustular psoriasis is considered a separate entity from plaque psoriasis and can be categorized as generalized pustular psoriasis (GPP), acrodermatitis continua of Hallopeau, or palmoplantar pustulosis (PPP). Current guidelines mostly include treatment options that have not been specifically developed for the treatment of pustular psoriasis. The majority of them does not have indication for the treatment of pustular psoriasis. Their effectiveness and safeness have been described in small cohort-based studies or case series with a low level of evidence. Previous studies evaluated treatment response through physician-based assessment but none reported patient satisfaction to treatment, quality of life and patient perception of disease severity during systemic therapies, particularly with biologics commonly used in plaque psoriasis. This study aimed to investigate patient satisfaction to treatment and patients' quality of life during treatment, correlating patient-reported outcomes with residual disease severity. Methods: A cross-sectional, cohort-based, single center study included patients affected by pustular psoriasis undergoing treatment with systemic agents. Demographic, clinical characteristics were collected. Treatment satisfaction as well as disease severity were assessed through dedicated assessment scores. Results: A total of 31 patients affected by GPP or PPP were included. Despite biologic treatment, 80.6% of patients continued to experience mild-to-severe disease activity, with discrepancies between patient and physician assessments. Patients reported a substantial impairment in their quality of life, with notable limitations in physical activity and emotional distress. Mental health conditions, such as depression and anxiety disorders, were common. Treatment satisfaction varied, with moderate scores for effectiveness and convenience. Only a small proportion of patients (41.9%) reported complete or high overall treatment satisfaction. GPP and PPP subcohorts exhibited similar quality of life and treatment satisfaction levels. Discussion: This study highlights the suboptimal control of PP despite biologic therapies, resulting in a significant impact on patients' quality of life and treatment satisfaction. The findings highlight the need for specific therapies and standardized guidelines for managing PP. New targeted therapies, such as spesolimab, hold promise for optimizing treatment satisfaction and improving patients' quality of life in this challenging condition. Future research should focus on refining treatment strategies to address the unmet needs of PP patients comprehensively.
ABSTRACT
BACKGROUND: Localization of atopic dermatitis (AD) in exposed areas such as the hands, head, and neck has been considered as a negative factor impacting on dupilumab response, although a comparison of exposed versus unexposed areas is not currently available. OBJECTIVES: The aim of this study is to evaluate the clinical response to dupilumab depending on the presence or persistency of AD skin manifestations in specific body areas. METHODS: The study retrospectively collected clinical and demographic data of adult patients affected by moderate to severe AD. Based on the anatomical sites involved, 5 subcohorts of patients were identified. RESULTS: A total of 41 patients were included in the study. Disease amelioration was detected during the study period, although baseline head/neck and hand localization was associated with a significantly lower likelihood of achieving an Eczema Area Severity Index (EASI) ≤1. In addition, patients with head/neck persistency showed a significantly lower response when compared to patients without persistency of head/neck AD in terms of both mean EASI and Dermatology Life Quality Index (DLQI) reduction. CONCLUSION: AD localization in exposed areas at the baseline and AD persistency at the head/neck may have a negative impact on certain treatment response parameters to dupilumab therapy.
Subject(s)
Antibodies, Monoclonal, Humanized , Dermatitis, Atopic , Adult , Antibodies, Monoclonal, Humanized/therapeutic use , Dermatitis, Atopic/complications , Dermatitis, Atopic/drug therapy , Humans , Retrospective Studies , Severity of Illness Index , Treatment OutcomeABSTRACT
A number of genes have been implicated in the pathogenesis of BCC in addition to the Hedgehog pathway, which is known to drive the initiation of this tumour. We performed in-depth analysis of 13 BCC-related genes (CSMD1, CSMD2, DPH3 promoter, PTCH1, SMO, GLI1, NOTCH1, NOTCH2, TP53, ITIH2, DPP10, STEAP4, TERT promoter) in 57 BCC lesions (26 superficial and 31 nodular) from 55 patients and their corresponding blood samples. PTCH1 and TP53 mutations were found in 71.9% and 45.6% of BCCs, respectively. A high mutation rate was also detected in CSMD1 (63.2%), NOTCH1 (43.8%) and DPP10 (35.1%), and frequent non-coding mutations were identified in TERT (57.9%) and DPH3 promoter (49.1%). CSMD1 mutations significantly co-occurred with TP53 changes (p = 0.002). A significant association was observed between the superficial type of BCC and PTCH1 (p = 0.018) and NOTCH1 (p = 0.020) mutations. In addition, PTCH1 mutations were significantly associated with intermittent sun exposure (p = 0.046) and the occurrence of single lesions (p = 0.021), while NOTCH1 mutations were more frequent in BCCs located on the trunk compared to the head/neck and extremities (p = 0.001). In conclusion, we provide further insights into the molecular alterations underlying the tumorigenic mechanism of superficial and nodular BCCs with a view towards novel rationale-based therapeutic strategies.
Subject(s)
Carcinoma, Basal Cell/genetics , Neoplasms, Basal Cell/genetics , Skin Neoplasms/genetics , Aged , Carcinoma, Basal Cell/pathology , Female , Humans , Male , Mutation/genetics , Neoplasms, Basal Cell/pathology , Promoter Regions, Genetic/genetics , Signal Transduction/genetics , Skin Neoplasms/pathologyABSTRACT
BACKGROUND: Few and small studies have described the management of immunomodulant/immunosuppressive therapies or phototherapy in atopic dermatitis (AD) patients during coronavirus disease 2019 (COVID-19) pandemic. METHODS: A national registry, named DA-COVID-19 and involving 35 Italian dermatology units, was established in order to evaluate the impact of COVID-19 pandemic on the management of adult AD patients treated with systemic immunomodulant/immunosuppressive medications or phototherapy. Demographic and clinical data were obtained at different timepoints by teledermatology during COVID-19 pandemic, when regular visits were not allowed due to sanitary restrictions. Disease severity was assessed by both physician- and patient-reported assessment scores evaluating itch intensity, sleep disturbances, and AD severity. RESULTS: A total of 1831 patients were included, with 1580/1831 (86.3%) continuing therapy during pandemic. Most patients were treated with dupilumab (86.1%, 1576/1831) that was interrupted in only 9.9% (156/1576) of cases, while systemic immunosuppressive compounds were more frequently withdrawn. Treatment interruption was due to decision of the patient, general practitioner, or dermatologist in 39.9% (114/286), 5.6% (16/286), and 30.1% (86/286) of cases, respectively. Fear of increased susceptibility to SARS-CoV-2 infection (24.8%, 71/286) was one of the main causes of interruption. Sixteen patients (0.9%) resulted positive to SARS-CoV-2 infection; 3 of them (0.2%) were hospitalized but no cases of COVID-related death occurred. CONCLUSIONS: Most AD patients continued systemic treatments during COVID pandemic and lockdown period, without high impact on disease control, particularly dupilumab-treated patients.
Subject(s)
COVID-19 , Dermatitis, Atopic , Adult , Communicable Disease Control , Dermatitis, Atopic/drug therapy , Dermatitis, Atopic/epidemiology , Humans , Italy/epidemiology , Pandemics , Registries , SARS-CoV-2ABSTRACT
PURPOSE: Introduction of cyclin-dependent inhibitors was a milestone in therapeutics for patients with estrogen receptor+/HER2- metastatic breast cancer. Despite the wide use of such agents and remarkable improvement of survival rates, drug-related adverse events are not yet fully characterized. We describe vitiligo-like lesions as a new adverse event occurring in patients with advanced breast cancer treated with cyclin-dependent inhibitors. METHODS: We performed an international retrospective study including patients with advanced breast cancer who developed vitiligo-like lesions during treatment with cyclin-dependent kinases 4 and 6 inhibitors, in the period January 2018-December 2019. Patients > 18 years, both males and females, were recruited at six Dermatology Departments located in Italy (3), France (1) and Greece (2). We evaluated epidemiological and clinical characteristics, impact on quality of life and outcome of vitiligo-like lesions in patients treated with cyclin-dependent 4 and 6 inhibitors. The percentage of skin involved by vitiligo-like lesions was assessed using the Body Surface Area (BSA) score. Changes in patients' quality of life were investigated through the evaluation of the Dermatology Life Quality Index (DLQI) questionnaire. RESULTS: Sixteen women (median age: 62.5 years; range 40-79 years) treated with cyclin-dependent kinases 4 and 6 inhibitors for advanced breast cancer presented with vitiligo-like lesions during follow-up visits. Cutaneous lesions consisted of white, irregular macules and patches located mainly on sun-exposed areas in 11/16 patients or diffuse to the entire body surface in 5/16. Cutaneous lesions clearly impaired the quality of life of patients tested (DLQI ≥ 10). CONCLUSIONS: We present for the first time, to our knowledge, a case series of vitiligo-like lesions developing in patients with advanced breast cancer treated with cyclin-dependent kinases 4 and 6 inhibitors. We showed that such lesions further impair the patients' quality of life and their treatment is challenging.
Subject(s)
Breast Neoplasms , Vitiligo , Adult , Aged , Breast Neoplasms/drug therapy , Breast Neoplasms/epidemiology , Female , France , Humans , Italy , Male , Middle Aged , Quality of Life , Retrospective Studies , Vitiligo/chemically induced , Vitiligo/epidemiologyABSTRACT
Basal cell carcinoma (BCC) represents the most commonly diagnosed human cancer among persons of European ancestry with etiology mainly attributed to sun-exposure. In this study we investigated mutations in coding and flanking regions of PTCH1 and TP53 and noncoding alterations in the TERT and DPH3 promoters in 191 BCC tumors. In addition, we measured CpG methylation within the TERT hypermethylated oncological region (THOR) and transcription levels of the reverse transcriptase subunit. We observed mutations in PTCH1 in 58.6% and TP53 in 31.4% of the tumors. Noncoding mutations in TERT and DPH3 promoters were detected in 59.2% and 38.2% of the tumors, respectively. We observed a statistically significant co-occurrence of mutations at the four investigated loci. While PTCH1 mutations tended to associate with decreased patient age at diagnosis; TP53 mutations were associated with light skin color and increased number of nevi; TERT and DPH3 promoter with history of cutaneous neoplasms in BCC patients. Increased reverse transcriptase subunit expression was observed in tumors with TERT promoter mutations and not with THOR methylation. Our study signifies, in addition to the protein altering mutations in the PTCH1 and TP53 genes, the importance of noncoding mutations in BCC, particularly functional alterations in the TERT promoter.