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Valentina Celoria,* Francois Rosset,* Valentina Pala, Paolo Dapavo, Simone Ribero, Pietro Quaglino, Luca Mastorino Dermatologic Clinic, Department of Medical Sciences, University of Turin, Turin, Italy*These authors contributed equally to this workCorrespondence: Valentina Celoria, Dermatologic Clinic, Department of Medical Sciences, University of Turin, Turin, Italy, Email valentina.celoria@edu.unito.itAbstract: The skin microbiome is made of various microorganisms, most of which have the function of protecting individuals from harmful pathogens, and they are involved in innate and adaptive immune responses. The skin acts as a physical and immunological barrier against external stimuli, including pathogens and physical damage. Changes in the composition of the skin microbiome can trigger inflammatory processes leading to inflammatory skin diseases in susceptible individuals. Psoriasis (PsO) is a chronic inflammatory disease with a multifactorial etiology, where breakdown of immune tolerance to cutaneous microorganisms is implicated in its pathogenesis. Dysregulation of the microbiome due to genetic and environmental factors plays a significant role in the development of psoriatic disease. Dermatologic conditions such as atopic dermatitis, acne, psoriasis, and rosacea have been associated with intestinal dysbiosis. The skin microbiota composition is crucial for the development of appropriate immune responses, and alterations in the skin microbiome can contribute to changes in physiology and susceptibility to skin diseases or inflammatory conditions. Understanding the microbial settlement of the skin and the network of interactions that occur throughout life is essential for comprehending the pathogenesis of skin diseases and developing innovative treatments. With this article we tried to explore the relationship between the human microbiome and psoriatic disease, shedding light on the functions of the microbiome and the inflammatory disease processes to identify additional therapeutic targets. This review aims to highlight the relationship between skin and gut microbiome functions and inflammatory processes in skin psoriasis and psoriatic arthritis (PsA). The goal is to facilitate future studies on the skin microbiome to identify potential novel therapies for patients with psoriatic disease.Keywords: psoriasis, skin microbiome, new therapies, gut microbiome, molecular precision medicines, next generation treatments

Gabriele Roccuzzo,* Luca Mastorino,* Giuseppe Gallo, Paolo Fava, Simone Ribero, Pietro Quaglino Department of Medical Sciences, Section of Dermatology, University of Turin, Turin, Italy*These authors contributed equally to this workCorrespondence: Giuseppe Gallo, Department of Medical Sciences, Section of Dermatology, University of Turin, Via Cherasco 23, Torino, Turin, 10126, Italy, Tel +39 0116335843 ; +39 0116335034, Email giuseppegallomd@gmail.comIntroduction: Folliculotropic mycosis fungoides (FMF) is the most frequent variant of mycosis fungoides (MF), with clinical features which differ from the classic form. As for therapeutic options, the latest guidelines on MF agree on a stage-driven strategy, in consideration of clinical presentation, symptom burden and patient’s comorbidities.Materials and Methods: A search on MEDLINE, PubMed, Scopus and Cochrane Library was conducted to gather the latest evidence on FMF clinical management. Manuscripts published in the last five years (January 2017–April 2022) were included. Our single-center experience was also described.Results: A total of 15 articles were analyzed, with a total of 432 patients (disease stage from IA to IVA2). The most widely-used treatment was psoralen ultra-violet A (PUVA) in monotherapy or in association with other drugs. Oral retinoid-based therapy was also described as a therapeutic option alone or in combination. Other therapy reported were based on Brentuximab Vedotin, Mogamulizumab, Carmustine, topical steroids, tazarotene and excimer laser, interferon, nitrogen mustard, imiquimod, systemic chemotherapy, extracorporeal photopheresis and stem cell transplantation.Discussion: FMF is characterized by specific clinical-pathologic features. Advanced forms assume characteristics more similar to classic MF (infiltrated plaques and nodules), whilst early stages can present in a wide range of clinical forms (acneiform lesions, follicular-like keratoses, erythematous patches). As for therapeutic options, in absence of specific guidelines, a high number of treatments are described in clinical practice, with variable results. Phototherapy in all its forms, especially as PUVA, appears to have the greatest initial therapeutic success. Retinoids, although widely used, appear to be poorly effective in monotherapy, particularly acitretin. Combination treatment with phototherapy seems to be advisable. Ionizing treatments, such as radiotherapy and TSEBT, appear effective, at least in the short term. Overall, an integrated approach is mandatory for the inconstant course of the disease and its multidisciplinary nature.Keywords: mycosis fungoides, folliculotropic mycosis fungoides, cutaneous lymphoma, primary cutaneous T-cell lymphoma, therapy

Mogamulizumab is a first‐in‐class IgG1k monoclonal antibody that selectively targets the chemokine receptor type 4. The drug has received Food and Drug administration authorisation for mycosis fungoides and Sézary syndrome following failure of at least one previous course of systemic therapy and now is available in Europe. One of the most common treatment‐related side effects observed has been the mogamulizumab‐associated rash (MAR), which affects up to a quarter of patients and is the most frequent adverse event leading to drug discontinuation. The aim of this study is to perform a systematic review of the literature on patients diagnosed with MAR and other mogamulizumab‐related cutaneous events to describe the clinical and histological characteristics, the management in clinical practice and to assess whether these events have prognostic implications. In total, 2073 records were initially identified through a literature search, 843 of which were duplicates. After screening for eligibility and inclusion criteria, 49 articles reporting mogamulizumab‐associated cutaneous events were included. Totally, 1516 patients were retrieved, with a slight male prevalence as for the available data (639 males and 570 females, i.e. 52.9% vs. 47.1%). Regarding the reported clinicopathological findings of the cutaneous reactions, the five most common patterns were spongiotic/psoriasiform dermatitis (22%), eruptions characterized by the presence of papules and/or plaques (16.1%), cutaneous granulomatosis (11.4%), morbilliform or erythrodermic dermatitis (9.4%) and photodermatitis (7.1%). Our results highlight how the majority of the reported cutaneous adverse events on mogamulizumab are of mild‐to‐moderate entity and generally manageable in clinical practice, though prompt recognition is essential and case‐by‐case assessment should be recommended. Future research will need to focus on the MAR prognostic implications and to identify genomic and molecular markers for a more rapid and accurate diagnosis. [ABSTRACT FROM AUTHOR]

Amelanotic/hypomelanotic melanoma (AHM) may be difficult to diagnose because of a lack of pigmentation. To evaluate whether dermoscopy can be useful for the diagnosis of early AHM, 133 digital dermoscopic images of lesions histopathologically diagnosed as amelanotic/hypomelanotic superficial spreading melanoma with ≤1 mm thickness (AHSSMs) (n = 27), amelanotic/hypomelanotic non‐melanocytic lesions (AHNMLs) (e.g., seborrhoeic keratosis and basal cell carcinoma) (n = 79), and amelanotic/hypomelanotic benign melanocytic lesions (AHBMLs) (e.g., compound and dermal nevi) (n = 27), were dermoscopically assessed by three blinded dermatologists. Using multivariate analysis, we found a significantly increased risk of diagnosing AHSSM versus AHNML and AHBML when the lesion was characterized by the presence of more than one shade of pink (odds ratio [OR] 37.11), irregular dots/globules (OR 23.73), asymmetric pigmentation (OR 8.85), and structureless pattern (OR 7.33). In conclusion, dermoscopy may improve early AHM detection, discriminating AHSSM from amelanotic/hypomelanotic non melanoma lesions. [ABSTRACT FROM AUTHOR]

Introduction: Ixekizumab proved to be effective and safe for psoriasis treatment in several randomized clinical trials and real‐life studies. Nevertheless, long‐term real‐world experiences are still lacking, with little data up to 4 years of treatment. Objectives: To analyse survival, effectiveness and safety of ixekizumab in a real‐life cohort of patients affected by moderate‐to‐severe psoriasis or psoriatic arthritis up to 260 weeks (5 years). Methods: We included all patients treated with ixekizumab from December 2017 to March 2021. Drug survival (DS) was analysed in patients at risk for up to 5 years. Cox analysis was adopted to evaluate possible predictive factors of discontinuation. Psoriasis Area Severity Index (meanPASI and PASI100, 90, and ≤3) was used as outcomes of effectiveness on observed patients at 16, 52, 104, 156, 208 and 260 weeks. Logistic regression was performed to identify possible predictive factors of response. Results: DS was 65.5% at 260 weeks, with being a super‐responder patient (achievement of PASI100 at 16 weeks and maintained at 28 weeks) correlated with less risk of discontinuation. PASI100, 90 and ≤3 was achieved by 54.1%, 60.5% and 73% of observed patients, respectively, at 16 weeks, and by 59.1%, 81.8% and 95.5%, respectively, at 260 weeks. High mean BMI was the only factor strongly associated with less achievement of the outcomes at the earlier time points: PASI100 at 16 weeks (OR 0.93, CI 0.87–0.98, p = 0.014) and at 104 weeks (OR 0.91, CI 0.84–0.98, p = 0.019), PASI90 achievement at 16 weeks (OR 0.94, CI 0.88–0.99, p = 0.028) and 104 weeks (OR 0.91, CI 0.83–0.99, p = 0.027), and PASI ≤3 (OR 0.86, CI 0.76–0.97, p = 0.018) at 104 weeks. No severe adverse events were observed. Conclusions: Ixekizumab showed high effectiveness and safety for up to 5 years, with survival of 2/3 of treated patients. Rapid response to treatment is predictive of long‐term response. [ABSTRACT FROM AUTHOR]