Blastic Plasmacytoid Dendritic Cell Neoplasm, from a Dermatological Point of View.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive hematological malignancy derived from the precursors of plasmacytoid dendritic cells. Although disease awareness has increased over time, BPDCN represents a rare disease with an aggressive clinical course and a dismal prognosis. Due to the overlap in clinical and histological features with a large spectrum of inflammatory and neoplastic diseases, BPDCN is difficult to diagnose. Furthermore, given the rarity of the disease, treatment options for BPDCN are limited, sometimes changing by practitioner and hospitals. Treatment options range from conventional chemotherapy to the recently approved biologic agent tagraxofusp and stem cell transplantation. Therefore, a multidisciplinary approach with coordination among dermatologists, pathologists, and hematologists is ultimately imperative to reach the correct diagnosis and management of BPDCN.

Natalizumab treatment during pregnancy in multiple sclerosis-clinical and bioethical aspects of an ongoing debate.

BACKGROUND: Natalizumab is an approved treatment for relapsing remitting multiple sclerosis; however, its safety during pregnancy is not formally proven. CASE PRESENTATION: We report a woman with multiple sclerosis being treated with natalizumab before pregnancy. After withdrawal of natalizumab, she suffered a severe, disabling rebound. In agreement with the patient, natalizumab was restarted during pregnancy. Our patient improved substantially and gave birth to a healthy boy. CONCLUSION: Use of natalizumab during pregnancy may be an option in highly active multiple sclerosis.

Impact of Upadacitinib on Atopic Keratoconjunctivitis Exacerbated by Dupilumab Treatment in Atopic Dermatitis Patients: A Prospective Dermatological and Ophthalmological Clinical Evaluation in Common Clinical Practice.

Introduction: Atopic dermatitis (AD) is a prevalent chronic inflammatory skin condition with a substantial impact on patients, particularly due to ocular involvement known as atopic keratoconjunctivitis (AKC). Current therapeutic approaches, such as dupilumab, often lead to conjunctivitis, prompting exploration of alternative treatments like upadacitinib. Methods: We collected dermatological and ophthalmological prospective clinical evaluations of six adults with moderate-to-severe AD, undergoing treatment with upadacitinib after discontinuation of dupilumab due to the onset of AKC during therapy and the worsening of dermatitis in particular in the head and neck region. Clinical evaluations, including EASI scores, itch and sleep NRS, DLQI, and ocular parameters, were performed at baseline (during screening assessment before switching to upadacitinib) and then at week 12 and week 24. Clinical evaluation of AKC was performed by a team of ophthalmologists. Results: Upadacitinib not only improved atopic dermatitis in terms of EASI, itching, and sleep NRS, but also demonstrated a notable reduction in ocular signs and symptoms, as indicated by the Visual Analogue Scale (VAS), the Efron scale, and the Ocular Surface Disease Index Symptom Severity (OSDISS) scores. Discussion: Our observation of common clinical practice underscores the substantial impact of biological and small-molecule therapies on AD, emphasizing the limitation posed by dupilumab-associated conjunctivitis. Switching to upadacitinib significantly improved both clinical and functional ocular outcomes, suggesting its potential as an alternative therapeutic option for AD patients with ocular involvement. Conclusion: The presented data provides insights into the complex interplay between systemic therapies and ocular manifestations in AD. Upadacitinib emerges as a promising option to address dupilumab-associated conjunctivitis, offering improved quality of life for patients.

Dupilumab for Treatment of Prurigo Nodularis: Real-Life Effectiveness for up to 84 Weeks.

(1) Background: Prurigo nodularis (PN) is a persistent and inflammatory dermatological condition characterized by chronic itching and the formation of hardened nodules, significantly impacting the affected individuals' quality of life and psychological well-being. The management of PN poses challenges due to the limited efficacy and undesirable side effects associated with current interventions. (2) Methods: This article examines sixteen patients affected by PN treated with dupilumab, a fully human monoclonal antibody targeting interleukin IL-4 and IL-13 signaling. This involves a retrospective descriptive statistical analysis. (3) Results and (4) Conclusions: In all patients, dupilumab proves to be an effective drug in achieving disease clearance, as indicated by all the parameters considered as assessed by both physicians and patients at each evaluation point (Week 6, Week 16, Week 32, Week 52, Week 68, and Week 84), in comparison to the initial baseline.

Efficacy and Safety of Dupilumab in the Treatment of Hand Eczema: A Retrospective Study.

Background: Hand eczema (HE) is a prevalent chronic condition that exerts a substantial and enduring adverse effect on quality of life (QoL) and imposes an economic burden on society. Managing HE poses challenges due to the limited effectiveness and potential adverse effects associated with many currently available topical and systemic treatments. Methods: This article examines twenty-one patients affected by HE treated with dupilumab, a fully human monoclonal antibody targeting interleukin IL-4 and IL-13 signaling. This involves a retrospective descriptive statistical analysis. Results: At week 6, HECSI-75 was achieved by 12 patients (57.9%). The proportion of patients meeting the HECSI-75 criteria steadily increased over the observation weeks, reaching 90% at week 16 and 100% at week 104. Furthermore, HECSI-90 and HECSI-100 were achieved by 75% and 60% of patients at week 16 and by 100% and 85% of patients at week 68, respectively. All patients who reached week 104 maintained complete disease remission according to HECSI 100. Conclusions: In all patients, dupilumab was shown to be an effective drug in achieving disease clearance, as indicated by all the parameters considered at each evaluation point (Week 6, Week 16, Week 32, Week 52, Week 68, Week 84, and Week 104), in comparison to the initial baseline.

Characterization of Super-Responder Profile in Chronic Plaque Psoriatic Patients under Guselkumab Treatment: A Long-Term Real-Life Experience.

Background: The term "super responder" identifies a group of patients who exhibit a rapid and optimal response to biological treatment compared to the overall treated population. The primary objective of our study is to characterize this subgroup of patients to enable the early identification of those who will respond most effectively to the proposed treatment while also evaluating clinical efficacy. Methods: This retrospective study evaluated 232 patients treated with guselkumab in monotherapy for at least 20 weeks between November 2018 and November 2023. Patients were divided into two groups: those who achieved complete clear skin (PASI = 0) during the first 20 weeks of treatment were defined as super responders (SRe) and non-super responders (nSRe) were the remaining patients. PASI was assessed at weeks 0, 4, and subsequently every eight weeks. Predictors of the SRe status were evaluated by univariate and multivariate logistic regression analyses. Results: The univariate analyses showed that patients with psoriatic arthritis at the baseline, bio-naïve patients, or those who had not received an interleukin (IL) 17 inhibitor as their last therapy before guselkumab administration were more likely to be super responders to the proposed treatment. Multivariate logistic analysis models suggested that the combination of psoriatic arthritis at the baseline and the bio-naïve condition was the strongest predictive model for the SRe status. At week 204, the main difference between the two groups concerned the achievement of PASI100, maintained by 86.8 of SRe compared to 62.8% of nSRe. Conclusions: The efficacy and safety of guselkumab are confirmed in our real-life experience. Identifying the SRe status will undoubtedly play a role in clinical practice and the therapeutic decision-making algorithm.

Evaluating the Clinical Meaning of Dermatology Life Quality Index Scores Between Different Phenotypes of Atopic Dermatitis in Patients Before and After Biologic Therapy With Dupilumab.

Background and Objective: Atopic Dermatitis (AD) is the most prevalent inflammatory skin disorder resulting in an intense impact on patients quality of life. The aim of this study is to evaluate the clinical meaning of the DLQI scores documented between different phenotypes of AD patients under biologic therapy with Dupilumab. Method: We conducted a retrospective analysis of 209 patients with AD treated with Dupilumab for 2 years. These patients were categorized into different clinical phenotypes. Severity of the disease was assessed by using the Eczema Area and Severity Index (EASI), Numerical Scale Rating (NRS) for sleep (NRS sleep), pruritus (NRS pruritus) and Dermatology Life Quality Index (DLQI) at baseline and subsequently at 4,12 and 24 months. Results: Our results show that the higher DLQI scores (mean: 18.6, range:9-30) achieved at T0 are associated with a prurigo nodularis AD pattern, while after 24 months (T3) of therapy with Dupilumab, the worst quality of life index results were reported in Flexural and Head-Neck combined clinical phenotypes. Conclusions: Quality of life is probably what matters most as an overall endpoint in AD. Assessing the clinical meaning of DLQI scores across different AD phenotypes could be a further aid when considering decision making factors in patient management.

Long-Term Persistence Rate of Secukinumab in Psoriatic Patients: A Six-Year Multicenter, Real-World Experience, Retrospective Study.

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.

Deucravacitinib, a selective tyrosine kinase 2 inhibitor, for the treatment of moderate-to-severe plaque psoriasis.

INTRODUCTION: Protein kinases play a crucial role in intracellular signaling pathways that lead to inflammation and cell proliferation. New understandings of the involvement of these metabolic pathways in the pathogenesis of psoriasis allowed the development of a new class of drugs. Unlike biologics, these compounds work by blocking intracellular targets involved in the immune response. AREAS COVERED: Deucravacitinib is an oral small-molecule inhibitor of TYK2 that binds the pseudokinase domain and locks the kinase in an inactive state by an allosteric mechanism, arresting TYK2-mediated signaling cascades and disabling the upregulation of proinflammatory genes implicated in psoriasis. The authors present the results of phase I-III clinical trials of deucravacitinib for the treatment of psoriasis. EXPERT OPINION: At week 16 about 56% of the patients treated with deucravacitinib achieved PASI75. No serious infections were reported, nor were thromboembolic events or laboratory abnormalities. Efficacy was reported to be persistent and safety profiles were shown to be consistent for up to 2 years. Deucravacitinib can potentially become a safe, effective, well-tolerated treatment for patients suffering from moderate-to-severe disease. Future studies and real-life experiences will be important to determine the exact role of this drug in the treatment of psoriasis.

Guselkumab for treatment of moderate-to-severe plaque psoriasis: real-life effectiveness and drug-survival for up to 148 weeks.

BACKGROUND: Real-world data are useful to guide the management of psoriasis. Here, we present data on the effectiveness and survival of guselkumab in moderate-to-severe chronic plaque psoriasis for up to 148 weeks. RESEARCH DESIGN AND METHODS: Cross-sectional study of 122 patients receiving guselkumab (100 mg at weeks 0 and 4, and then every 8 weeks thereafter) for>12 weeks, from November 2018 to April 2022. MAIN OUTCOME MEASURES: Clinical features and drug survival were analyzed up to 148 weeks. RESULTS: Obese patients (32.8%) and those receiving prior biologics (64.8%) were included. Guselkumab treatment was associated with a rapid decrease in PASI, from 16.2 to 3.2 at week 12, and long-term improvements in all subgroups (97.6%, 82.9%, and 63.4% of patients, respectively, achieved PASI 75, 90, and 100 after 148 weeks). More non-obese than obese patients achieved PASI 100 at week 148 (86.4% vs 38.9%), as did bio-naïve vs bio-experienced patients (86.7% vs 50.0%). Previous biologic therapy was a negative prognostic factor for achieving PASI 100 over the long-term by multivariate analysis (p = 0.005). Overall, 96% of patients were on treatment after 2 years. CONCLUSIONS: Real-world data confirm the long-term effectiveness of guselkumab in patients with psoriasis.