Ixekizumab as a successful treatment in pediatric generalized pustular psoriasis Maria Esposito, Paolo Antonetti, Emanuele Vagnozzi, Andrea De Berardinis, Roberta Bertelli, et al. Italian Journal of Pediatrics, 2025 Background Generalized Pustular Psoriasis (GPP) is an autoinflammatory, multisystemic disease, characterized by widespread eruption of neutrophilic pustules on erythematous base, accompanied by systemic symptoms such as fever, leukocytosis, arthralgia, and general malaise. Globally, the disease is rare, particularly in children. If not adequately diagnosed and treated, systemic inflammation and multiorgan involvement can be life-threatening. The pathogenesis of GPP mainly involves the innate immune system, with inflammatory processes and neutrophil activation driven primarily by IL-36, but also by IL-1, TNF-alpha, IL-17 A. In particular, IL-17 A acts as a potent inducer of neutrophil recruitment. We report the case of a 7-years-old girl with GPP successfully treated with Ixekizumab, an IL-17 A antagonist. Case presentation A 7-years-old girl with an history of plaque psoriasis came to our attention for the sudden appearance of erythematous patches surmounted by pustules on the trunk and lower limbs, following repeated episodes of purulent tonsillitis. We started therapy with cyclosporine at a dosage of 3,5 mg/kg/day, with no clinical benefit and progression of manifestations to a sub-erythrodermic state after 2 weeks. Blood tests showed neutrophilic leukocytosis, and the patient experienced hyperpyrexia and malaise. Since ixekizumab was recently approved for pediatric use in patients with moderate to severe plaque psoriasis, we started therapy with 80 mg Ixekizumab, combined with prednisone at a dosage of 12.5 mg/day, gradually tapered until discontinuation after 15 days. A second dose of Ixekizumab 40 mg was administered at week-4, according to the indication of ixekizumab in pediatric plaque psoriasis. At week-8 the patient achieved complete remission of skin manifestations and normalization of blood count. After achieving a stable remission, at week 36 we decided to increase the administration interval to 6 weeks. The patient is still on therapy with ixekizumab 40 mg every 6 weeks, maintaining complete remission during a 52-week follow-up, without safety concerns. Conclusions This report supports the use of ixekizumab as a safe and effective option, both in the short and long-term, in the treatment of GPP, even at pediatric age. Larger studies are needed to confirm this positive, real-life experience.
Clinical course of atopic dermatitis after dupilumab discontinuation: a multicentre real-world study Francesca Barei, Stefano Macchi, Paolo Calzari, Simone Ribero, Michela Ortoncelli, et al. Clinical and Experimental Dermatology, 2025 Background Limited data exist on the clinical course of atopic dermatitis (AD) after the discontinuation of dupilumab. Objectives To assess disease progression following dupilumab discontinuation. Methods A multicentre, retrospective study was conducted on 208 patients with severe AD who discontinued dupilumab for reasons unrelated to inefficacy. The Eczema Area and Severity Index (EASI), pruritus numerical rating scale (P-NRS), Atopic Dermatitis Control Tool (ADCT) and Dermatology Life Quality Index (DLQI) were used to assess disease activity after discontinuation. Kaplan–Meier analysis was used to estimate the time and probability of disease worsening (defined as EASI > 7.0, EASI increase ≥ 6.6, P-NRS ≥ 4, P-NRS increase ≥ 4, ADCT ≥ 7, ADCT increase ≥ 5, or DLQI increase ≥ 4), as well as the need to restart systemic treatment. Results The main reasons for discontinuing dupilumab were clinical remission or good clinical control (43.3%), patient’s decision (11.1%) and pregnancy or desire to become pregnant (20.7%). Patients with a family history of AD or nonclassical phenotypes had a significantly higher likelihood of disease worsening. A significant portion (42.8%) of patients resumed systemic treatment within a median time of 47 weeks. They had a baseline median EASI score of 10.0 and a median P-NRS of 6.0. The probability of resuming systemic treatment was 25% at 31 weeks and 50% at 94 weeks. Reinitiation of dupilumab significantly improved EASI and P-NRS scores within 16 weeks. Conclusions Discontinuing dupilumab is associated with disease recurrence in some patients, especially those with a family history or nonclassical AD. Dupilumab reinitiation is effective, leading to significant clinical improvements and supporting its use after treatment interruption.
Clinical and Ultrasonographic Assessment of Nail Psoriasis: A Comprehensive Study Maria Esposito, Lina Maria Magnanimi, Paolo Antonetti, Andrea De Berardinis, Cristina Pellegrini, et al. Dermatology Practical and Conceptual, 2025 Introduction: In patients with plaque type psoriasis (PSO), the progression to psoriatic arthritis (PsA) exacerbates the disease's impact and increases disability risk. Nail psoriasis (NP) affects up to 90% of PSO patients with a wide spectrum of clinical features and is a significant predictor of enthesitis, often associated with early PsA stages. Objective: This study aimed to clinically and ultrasonographically evaluate nail units in PSO patients, focusing on differences between those with/without PsA and those with/without onychopathy. Methods: Sixty patients were enrolled (23/60 PSO-37/60 PSO and PsA). PSO and PsA patients were evaluated and compared as well as patients with/without diagnosis of nail psoriasis in this cross-sectional single-center study. Nail abnormalities were evaluated by high frequency ultrasound (HFUS) using high frequency probes (27 MHz). After a descriptive assessment, the Nail Psoriasis Severity Index (NAPSI) and the Brown University Nail Enthesis Scale (BUNES) were used to clinically and ultrasonographically assess nails. Results: HFUS evaluation identified a spectrum of nail and blood flow alterations. Nail disease was characterized by median NAPSI 16 (range 28), median BUNES morphometry 1.5 (range 0.9), and median BUNES power Doppler (PD) 2.2 (range 4.03). Among the studied sample, 43/60 (71.7%) presented nail psoriasis, with 69.7% presenting coexisting PsA as compared to PSO patients (30.3%) (p = 0.04). Conclusion: Our findings highlight the importance of close collaboration between dermatologists and rheumatologists in the evaluation of PSO patients, taking advantage of both clinical and ultrasonographic assessment of nail damage.
Upadacitinib Monotherapy in Vitiligo Associated with Atopic Dermatitis: Killing Two Birds with One Stone Lina Maria Magnanimi, Andrea De Berardinis, Maria Esposito, Maria Concetta Fargnoli Case Reports in Dermatology, 2025 Introduction: An increased risk of developing vitiligo has recently been described in patients with atopic dermatitis (AD). Vitiligo and AD can be associated because of shared pathogenetic pathways, including alterations in the Janus kinases/signal transducer and activator of transcription (JAK/STAT) signaling, suggesting JAK inhibitors as a promising new therapeutic approach in vitiligo. Case Presentation: We describe a 25-year-old woman diagnosed with AD since childhood and subsequent onset of slowly progressive vitiligo at the age of 16. Systemic therapy with JAK1 inhibitor upadacitinib 15 mg daily was started, after a medical and laboratory evaluation to exclude pregnancy and other contraindications. Progressive improvement of AD was observed after the first weeks of treatment with clinical remission at week 16. At the same time, clear improvement of vitiligo was observed with an almost complete remission achieved at week 28 of treatment. Conclusion: The remission of both AD and vitiligo achieved with upadacitinib monotherapy supports the therapeutic utility of inhibition of JAK 1 signaling in these patients.
Assessment of gene signatures following the inhibition of IL-23: a study to evaluate the mechanistic effects behind the clinical efficacy of guselkumab in patients with psoriatic arthritis Mirco Mastrangelo, Piero Ruscitti, Manfredo Bruni, Eleonora Lucantonio, Andrea De Berardinis, et al. Frontiers in Immunology, 2025 ObjectivesThe aim of this study was to evaluate the transcriptome of peripheral blood mononuclear cells (PBMCs) derived from patients affected by psoriasis (PSO) and psoriatic arthritis (PSA) following treatment with guselkumab, an interleukin (IL)-23 inhibitor.MethodsmRNA was extracted by PBMCs, before and after 24 weeks of treatment with guselkumab, and RNA sequencing was performed in paired-end mode by Illumina technology using the Novaseq6000 platform. log2FoldChange > 1 and padj < 0.05 were the established cutoff to discriminate genes differentially expressed between pre- and post-therapy. For annotation and predictive enrichment analysis of deregulated genes in biological pathways, RStudio was used, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were queried. Cytoscape_v3.10.3 was used for the development of the network between deregulated genes.ResultsSix naïve active patients with PSO and PSA, diagnosed with a duration <2 years, were assessed before and after 24 weeks of treatment with guselkumab. Performing the quality check and filtering analyses, we found 506 transcripts deregulated between pre- and post-therapy, of which 129 were upregulated and 377 were downregulated. The most upregulated mRNAs included SYTL3, CPT1A, TMEM208, GINS4, and TNFRSF13C. The most downregulated mRNAs included CCR2, TPT1, MYCBP, CMPK1, and TMEM65. Enrichment with the GO database showed the following main deregulated processes: “protein targeting”, “the establishment of protein localization to membrane”, and “metabolism of fatty acids”. The analysis of the main macro-process showed the several pathways deregulated after therapy, including signaling related to ethanol metabolism, thermogenesis, oxidative phosphorylation, and fatty acid metabolism (KEGG).ConclusionsOur findings may give further insights into manipulated mechanistic pathways by IL-23 inhibition in patients with PSO and PSA.
Exploring the interplay of atopic dermatitis severity with sleep and mental health: a case-control study in adult patients Maria Esposito, Giulia Amicucci, Federico Salfi, Cristina Pellegrini, Andrea De Berardinis, et al. Postgraduate Medicine, 2024 OBJECTIVES Atopic dermatitis (AD) is a chronic inflammatory skin disease often associated with non-atopic comorbidities. Recently, a severity-dependent relationship between AD and sleep/mental health diseases has been proposed. However, few studies investigated these comorbidities and their association with AD severity through validated questionnaires. This study aimed to use a set of validated instruments to assess the impact of AD on sleep and psychological disorders and estimate the association of itch and AD severity with sleep disorders and psychological symptoms, distinguishing between clinical-oriented and patient-oriented measures. METHODS We conducted a case-control study, recruiting 57 adult AD patients (mean age ± std. dev. 34.28 years ± 13.07; 27 males) matched for age and sex with 57 healthy adults (34.39 years ± 13.09; 27 males). To investigate the differences in sleep quality, insomnia, depression, and anxiety between the two groups, we performed independent sample t-Tests. Moreover, we conducted univariate linear regression analyses to examine the relationship between itch and objective/subjective severity of AD and sleep quality, insomnia, and psychological symptoms. RESULTS AD patients reported lower sleep quality (p = 0.002), more severe insomnia (p = 0.006) and depression (p = 0.013), and higher stress levels than healthy adults (p = 0.049). Itch intensity was linked to sleep disturbances and psychological symptoms (R2range = 0.13-0.19, prange = 0.02-<0.001). Objective and subjective AD severity were similarly associated with worse sleep quality (R2 = 0.26, p < 0.001; R2 = 0.24, p < 0.001; respectively), anxiety (R2 = 0.15, p = 0.04; R2 = 0.17, p = 0.001; respectively), and self-perceived stress (R2 = 0.10, p = 0.02; R2 = 0.07, p = 0.049; respectively). However, subjective AD severity was more strongly associated with insomnia (R2 = 0.31, p < 0.001) and depression (R2 = 0.20, p < 0.001) than clinical-oriented AD severity (R2 = 0.19, p < 0.001; R2 = 0.05, p = 0.098; respectively). CONCLUSIONS The study demonstrated poor sleep quality and high levels of insomnia, depression, and stress in AD patients, with an aggravated psychological status for adults with more severe skin disease. We suggest implementing a multidisciplinary approach to AD management/treatment that considers objective and subjective measures of disease severity.
The role of insomnia in the vulnerability to depressive and anxiety symptoms in atopic dermatitis adult patients Federico Salfi, Giulia Amicucci, Michele Ferrara, Daniela Tempesta, Andrea De Berardinis, et al. Archives of Dermatological Research, 2023 Atopic dermatitis (AD) is a common inflammatory chronic skin disease typically associated with atopic comorbidities and other non-atopic conditions such as sleep disturbances, and mood/anxiety disorders. A growing literature proposed a crucial role of sleep disturbances in the development of mental health problems in AD. We tested this assumption by mediation model analyses in adult AD patients.A total of 57 patients (mean age ± std. dev., 34.28 ± 13.07 years; 27 males; range 18–67 years) diagnosed with AD participated in a cross-sectional study. We evaluated self-perceived severity of AD, insomnia, depression, and anxiety symptoms using validated questionnaires: the Patient-Oriented Eczema Measure (POEM), the Insomnia Severity Index (ISI), the Beck Depression Inventory-second edition (BDI-II), and the Generalized Anxiety Disorder-7 scale (GAD-7), respectively. Two mediation models were performed, testing the mediation effect of insomnia symptoms on the relationship between AD severity and depression (model 1) and anxiety (model 2). AD symptoms, as expressed by POEM, were positively associated with insomnia, depression, and anxiety severity. Insomnia fully mediated the effect of AD severity on depression and anxiety. Specifically, insomnia accounted for 81.64% of the relationship between atopic eczema severity and depression, and for 81.84% of the effect of AD severity on anxiety symptoms. The present study proposed a critical role of insomnia in predisposing adult AD patients to experience depression and anxiety. Early interventions focused on treating sleep disturbances could indirectly be beneficial on mental health of patients with AD, counteracting the onset and exacerbation of anxiety and depression disorders.
