The ATTRACT study: screening for the early identification of axial psoriatic arthritis in a cohort of Italian psoriatic patients.

OBJECTIVE: There is growing interest in the early identification of patients with axial psoriatic arthritis (axPsA). We aimed to evaluate whether a dermatology-based screening strategy could help to identify axPsA patients. METHODS: The dermatologist-centered screening (DCS) questionnaire was administrated by Dermatologists to consecutive patients fulfilling the inclusion criteria (1. age ≥ 18 years and 2. clinical diagnosis of psoriasis made by a dermatologist) to identify patients eligible (affirmative answers 1-3c of the DCS) for rheumatological evaluation. Clinical, laboratory, genetic, and imaging data were collected from all referred patients. RESULTS: Among the 365 patients screened, 265 fulfilled the inclusion criteria and 124/265 (46.8%) were eligible for rheumatological referral. Diagnosis of axPsA, with or without peripheral PsA (pPsA), was made in 36/124 (29.0%) patients; pPsA without axial involvement was found in 21/124 (16.9%) patients. Back pain at screening was recorded in 174 (66%) patients, with 158 (60%) reporting a back pain duration longer than 3 months, and 140 (53%) reporting back pain onset before the age of 45. Active inflammatory and/or structural post-inflammatory changes in the sacroiliac joints and/or spine were observed in all axPsA patients.Patients with PsA showed a numerically longer duration of back pain and higher CRP levels in comparison with patients with Pso without PsA. CONCLUSION: The DCS tool proved to be a valuable screening strategy for detecting and characterizing patients with axPsA in a real-life cohort of psoriasis patients in a dermatological setting and helped to identify a substantial number of patients affected by undiagnosed pPsA.

Skin, Autoimmunity and Inflammation: A Comprehensive Exploration through Scientific Research.

Human skin, as the body's largest organ, orchestrates a multifaceted interplay of cellular interactions that regulate essential physiological processes, including inflammation, immune responses, wound healing, and angiogenesis [...].

miRNAs, Mesenchymal Stromal Cells and Major Neoplastic and Inflammatory Skin Diseases: A Page Being Written: A Systematic Review.

Micro RNAs (miRNAs) are a type of non-coding RNA (ncRNA) and typically interact with specific target mRNAs through complementary base pairing, affecting their translation and/or stability. MiRNAs regulate nearly all cellular functions, including the cell fate of mesenchymal stromal cells (MSCs). It is now accepted that various pathologies arise at the stem level, and, in this scenario, the role played by miRNAs in the fate of MSCs becomes of primary concern. Here we have considered the existing literature in the field of miRNAs, MSCs and skin diseases, classified as inflammatory (such as psoriasis and atopic dermatitis-AD) and neoplastic (melanoma and non-melanoma-skin-cancer including squamous cell and basal cell carcinoma) diseases. In this scoping review article, the evidence recovered indicates that this topic has attracted attention, but it is still a matter of opinion. A protocol for this review was registered in PROSPERO with the registration number "CRD42023420245". According to the different skin disorders and to the specific cellular mechanisms considered (cancer stem cells, extracellular vesicles, inflammation), miRNAs may play a pro- or anti-inflammatory, as well as a tumor suppressive, or supporting, role, indicating a complex regulation of their function. It is evident that the mode of action of miRNAs is more than a switch on-off, and all the observed effects of their dysregulated expression must be checked in a detailed analysis of the targeted proteins. The involvement of miRNAs has been studied mainly for squamous cell carcinoma and melanoma, and much less in psoriasis and AD; different mechanisms have been considered, such as miRNAs included in extracellular vesicles derived both from MSCs or tumor cells, miRNAs involved in cancer stem cells formation, up to miRNAs as candidates to be new therapeutic tools.

New Insight into the Molecular Pathomechanism and Immunomodulatory Treatments of Hidradenitis Suppurativa.

Hidradenitis suppurativa (HS) is an immune-mediated inflammatory disorder characterized by deep-seated nodules, abscesses, sinus tracts and scars localized in the intertriginous areas. It is accompanied by pain, malodourous secretion and a dramatically decreased quality of life. Although the pathogenesis has not been entirely elucidated, the primary event is follicular hyperkeratosis of the pilosebaceous apocrine unit. Since the registration of the tumor necrosis factor-alpha inhibitor Adalimumab in 2015, several cytokines have been implicated in the pathomechanism of HS and the research of novel therapeutic targets has been intensified. We provide an update on the inflammatory cytokines with a central role in HS pathogenesis and the most promising target molecules of future HS management.

Vitiligo, from Pathogenesis to Therapeutic Advances: State of the Art.

Vitiligo is an acquired hypopigmentation of the skin due to a progressive selective loss of melanocytes; it has a prevalence of 1-2% and appears as rounded, well-demarcated white macules. The etiopathology of the disease has not been well defined, but multiple factors contribute to melanocyte loss: metabolic abnormalities, oxidative stress, inflammation, and autoimmunity. Therefore, a convergence theory was proposed that combines all existing theories into a comprehensive one in which several mechanisms contribute to the reduction of melanocyte viability. In addition, increasingly in-depth knowledge about the disease's pathogenetic processes has enabled the development of increasingly targeted therapeutic strategies with high efficacy and fewer side effects. The aim of this paper is, by conducting a narrative review of the literature, to analyze the pathogenesis of vitiligo and the most recent treatments available for this condition.

Latest combination therapies in psoriasis: Narrative review of the literature.

Biological therapies revolutionized the treatment of many chronic inflammatory skin diseases, first of all psoriasis, thanks to their high efficacy and the reduced number of side effects. However, the use of a single biologic drug does not always provide complete control of the disease or associated comorbidities over time. The first biological drugs used for the treatment of psoriasis, tumor necrosis factor alpha inhibitors, have long been used in combination with traditional topical and systemic therapies to induce a complete remission of the disease that could not be achieved with innovative drug alone. Even with the advent of new biological therapies with more precise molecular targets, the challenge of using combination therapies remained. Psoriatic patients often have major comorbidities, such as arthritis, inflammatory bowel disease, uveitis or have other concomitant conditions such as chronic spontaneous urticaria and atopic dermatitis, which may require different biologic treatments than those indicated in psoriasis. The objective of this article is, through a comprehensive revision of the literature, to analyze in which cases the use of the combination of the latest therapies for psoriasis may be useful.

Should we be concerned about gastrointestinal-related adverse events in patients with plaque psoriasis receiving secukinumab therapy? A retrospective, real-life study.

Real-world secukinumab gastrointestinal-related adverse events (GIRAE) data in psoriatic patients treated with secukinumab are lacking. A descriptive, retrospective study was performed by reviewing the medical records of patients who received secukinumab for plaque psoriasis for at least 1 year and who made a follow-up visit to the dermatology clinic of "Ospedali Riuniti Umberto I" in Ancona between December 1, 2021, and March 31, 2022. The patients' medical history and clinical data were collected at T0, before treatment, and at T1, corresponding to the last follow-up visit. Special attention was given to gastrointestinal adverse events (GIRAE). A total of 108 patients were included in the study. At baseline median PASI was 14.8 (range 2.2-27, SD 6.1), and median DLQI was 9.3 (5-16, SD 2.6). The median PASI for treated patients was 0.7 (0-3, SD 0.8; p < 0.00) 1and median DLQI was 0.3 (0-1, SD 0.5; p < 0.001). At T1 54/114 patients (50%) reached PASI100, of the other 54, 48 (88.9%) reached PASI 90 while the other six discontinued for secondary ineffectiveness. Only three patients reported a GIRAE (diarrhea), however, when screened, no IBD was found. Consistent with data in the literature, secukinumab is an effective and safe drug for the treatment of plaque psoriasis also in a real-life experience context. There should be no concern in choosing the drug for fear of possible IBDs-related GIRAE if there is no personal history or familiarity for IBDs.

Biological Treatments for Pediatric Psoriasis: State of the Art and Future Perspectives.

Psoriasis is a chronic systemic inflammatory disease that primarily affects the skin and is associated with multiple comorbidities with a considerable reduction in quality of life of affected patients. One-third of psoriasis cases begin in childhood and are associated with significant medical comorbidities such as obesity, metabolic syndrome, arthritis, and psychiatric disorders. In addition, because of its chronic nature and frequent relapses, psoriasis tends to require long-term treatment. Treatment of pediatric psoriasis usually involves the same methods used for adults. However, most treatments for pediatric psoriasis are used off-label, and research in this regard is still lacking. Targeted therapies involving the use of newly developed biologic drugs are also increasingly being applied to childhood psoriasis. This review summarizes the clinical features of pediatric psoriasis and focuses mainly on the updated concepts of pathogenesis and biological treatments of pediatric psoriasis.

Mesenchymal Stem Cells and Psoriasis: Systematic Review.

Mesenchymal Stem Cells (MSCs) are multipotent non-hematopoietic stromal cells found in different body tissues such as bone marrow, adipose tissue, periosteum, Wharton's jelly, umbilical cord, blood, placenta, amniotic fluid, and skin. The biological behavior of MSCs depends mainly on their interaction with the microenvironment in which they are found, whose quality deeply influences the regenerative and immunomodulatory properties of these cells. Several studies confirm the interaction between MSCs and inflammatory microenvironment in the pathogenesis of psoriasis, designating MSCs as an important factor driving psoriasis development. This review aims to describe the most recent evidence on how the inflammatory microenvironment that characterizes psoriasis influences the homeostasis of MSCs and how they can be used to treat the disease.

The efficacy of in vivo administration of Apremilast on mesenchymal stem cells derived from psoriatic patients.

INTRODUCTION: Psoriasis cellular hallmarks, such as the imbalance between Th1/Th17 and Th2 cytokines and the dysregulated expression of vascular endothelial growth factor (VEGF), inducible nitric oxide synthase, (iNOS) and indoleamine 2,3-dioxygenase (IDO), are all detectable in mesenchymal stem cells (MSCs) suggesting that psoriasis originates at mesenchymal level. AIM OF THE STUDY: In this scenario, MSCs may become the new therapeutic target and interest in the effects of traditionally used drugs, such as Apremilast, on MSCs has greatly increased. MATERIALS AND METHODS: MSCs from control subjects (C-MSCs) and from psoriatic patients before (PsO MSCs T0) and after in vivo treatment with Apremilast (PsO-MSCs T12) were isolated and characterized; subsequently, the effects of Apremilast on VEGF, iNOS and IDO expression were evaluated by immunocytochemistry (ICC). The expression of VEGF, iNOS and IDO was also detected in skin sections by immunohistochemistry (IHC). RESULTS: The results indicate that in vivo administration of Apremilast is able to drive the altered profile of PsO-MSCs towards a more physiological pattern. In skin sections, the role of Apremilast is evident in reducing VEGF, iNOS and IDO expression. CONCLUSION: Apremilast treatment influences the expression of VEGF, iNOS and IDO not only by keratinocytes but also by MSCs, restoring their intrinsic profile and their natural anti-inflammatory action, and decreasing the auto-inflammatory process that underpins the development of psoriasis.

Long-term efficacy and safety of apremilast in the treatment of plaques psoriasis: A real-world, single-center experience.

Apremilast is a small molecule approved for the treatment of plaques psoriasis and adult psoriatic arthritis. Pivotal studies have demonstrated short and long term efficacy and safety of apremilast but few data in real life are still available. The aim of this study is to report the efficacy and safety results of apremilast in clinical practice in patients with moderate-to-severe plaque psoriasis, focusing on therapeutic results obtained after 24 and 52 weeks of treatment. From May 2018 to December 2018, 40 patients with plaques psoriasis have been enrolled. Psoriasis Area Severity Index (PASI), body surface area, Physician Global Assessment, and Dermatology Life Quality Index (DLQI) were performed at baseline at 24 (W24) and 52 (W52) weeks after treatment initiation. Primary endpoint was to evaluate the percentage of patient that achieved PASI 75, PASI 90 and PASI 100 at week 24 and 52 of treatment. Additional measure of efficacy was percentage of patients reaching the minimal disease activity (MDA = PGA0/1 and DLQI 0/1) after 24 and 52 weeks of treatment. As secondary endpoint, we evaluated the percentage of patient that achieved DLQI 0-1 at W24 and W52, and long-term safety of apremilast. The percentage of patients who achieved PASI75, PASI90 and PASI100 was 47.5%, 30% and 10% and 25%, 35% and 10% at W24 and W52 respectively. About the half of the reported patients reached MDA at W24 (n = 21) and at W52 (n = 20). The 60% of patients achieved and maintained DLQI 0-1 at W24 until W52. Diarrhea, nausea, headache, insomnia, and other AEs have been reported by 28 patients. Apremilast in real life experience confirmed the levels of efficacy and safety obtained in pivotal trials. In particular, the good initial response to the treatment is predictive of the maintenance or improvement of the outcome over W52. The efficacy is supported by an excellent safety profile even in frail patients.

Telogen effluvium related to post severe Sars-Cov-2 infection: Clinical aspects and our management experience.

Telogen effluvium (TE) is one of the most common form of hair loss in women. Many triggers have been identified, as stress, drugs, trauma, endocrine disease, nutritional deficiencies, and febrile states. We report three cases of TE occurred after severe Sars-Cov-2 infection and provide our clinical management, according to Sars-Cov-2 hygiene measures. Only one case report has been found in the literature associating anagen effluvium during severe Sars-Cov-2 infection. Other studies reported the exacerbation of a preexisting TE, correlated to the stress of lockdown. In our cases, patients never had a TE diagnosis before and did not report previous evident hair loss. TE can be associated with post severe Sars-Cov-2 infection. From our revision of the literature, this is the first case-series describing TE in post severe Sars-Cov-2 patients. Further studies are needed to evaluate the relationship between TE and Sars-Cov-2 infection.

Saliva Proteomics as Fluid Signature of Inflammatory and Immune-Mediated Skin Diseases.

Saliva is easy to access, non-invasive and a useful source of information useful for the diagnosis of serval inflammatory and immune-mediated diseases. Following the advent of genomic technologies and -omic research, studies based on saliva testing have rapidly increased and human salivary proteome has been partially characterized. As a proteomic protocol to analyze the whole saliva proteome is not currently available, the most common aim of the proteomic analysis is to discriminate between physiological and pathological conditions. The salivary proteome has been initially investigated in several diseases: oral squamous cell carcinoma and oral leukoplakia, chronic graft-versus-host disease, and Sjögren's syndrome. Otherwise, salivary proteomics studies in the dermatological field are still in the initial phase, thus the aim of this review is to collect the best research evidence on the role of saliva proteomics analysis in immune-mediated skin diseases to understand the direction of research in this field. The results of PRISMA analysis reported herein suggest that human saliva analysis could provide significant data for the diagnosis and prognosis of several immune-mediated and inflammatory skin diseases in the next future.

Management of patients with hidradenitis suppurativa during the COVID-19 pandemic: Risk and benefit of immunomodulatory therapy.

Coronavirus disease 2019 (COVID-19) is a clinical syndrome caused by a new coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Italy has been the first nation affected by the coronavirus pandemic and is the second in the number of reported deaths in the European Union. In the United Hospital of Ancona, a specialist outpatient clinic dealing with diagnosis and treatment of immunomediated skin diseases has been operating since 1985, and 291 patients with hidradenitis suppurativa (HS) are currently being treated. Several cutaneous immunomediated diseases, including HS, are treated with biologic and nonbiologic immunosuppressive and immunomodulatory drugs. Since the end of February 2020, when the SARS-CoV-2 pandemic had already spread in most of Italy, a task force comprised of seven specialists has been set up with the aim of addressing problems relating to the specific risk for this class of patients in relation to SARS-CoV-2 infection and immunosuppressive ongoing therapy. In this article, the management of HS disease during the COVID-19 pandemic is discussed. The main goal was to evaluate the risk/benefit in modulating treatment taking into consideration patients' risk of exposure to SARS-CoV-2 virus.

Combined treatment of palmar hyperhidrosis with botulinum toxin type A and oxybutynin chloride: Results of a clinical, multicenter, prospective study.

Oxybutynin chloride and botulinum toxin type A (BTX-A) have demonstrated to be effective treatments for primary palmar hyperhidrosis (PPH); however, both of them are not completely free from local and/or generalized side effects. Primary aim of this study is to compare efficacy and safety of a sequencing administration of oral oxybutynin chloride after BTX-A injections vs oral oxybutynin chloride in monotherapy in patients with PPH. Secondary aim is to evaluate if the sequencing approach can allow the control of hyperhidrosis with lower dose of oral oxybutynin. Patients enrolled were compared for short- and long-term efficacy and safety of treatments. Effectiveness was evaluated through the Hyperhidrosis Disease Severity Scale (HDSS), and the Dermatology Life Quality Index (DLQI) score; safety was assessed through collection of the adverse events reported by patients both at baseline, at 24 and 52 weeks. Patients receiving sequencing treatment showed significant greater improvement than patients receiving oxybutynin chloride alone at T24 (HDSS P = .0076 and DLQI P = .0139) and T52 (HDSS P = .0387 and DLQI P = .0087). The dose of oxybutynin chloride useful to control hyperhidrosis was lower, and retention rate to the treatment was higher in patients receiving sequencing treatment (P = .001), than patients receiving monotherapy (P = .04). A sequencing therapeutic approach to palmar hyperhidrosis increases both efficacy and safety compared with the use of oral oxybutynin chloride alone, and allows clinicians to keep lower dosage of oxybutynin chloride reducing generalized side effects and increasing the retention rate to the treatment.

Global coronavirus pandemic (SARS-CoV-2): Past, present, and future of pediatric dermatology.

Two months have passed since the World Health Organization (WHO) declared the pandemic of the Coronavirus Disease 19 (COVID-19), caused by the SARS-CoV-2 virus, on 11 March 2020. Medical and healthcare workers have continued to be on the frontline to defeat this disease, however, continual changes are being made to their working habits which are proving to be difficult. Although the skin is not the main target of the SARS-CoV-2 infection, it is strongly involved both directly and indirectly, in many aspects of dermatological disease management, and particularly in pediatric dermatology. In this manuscript, our goal was to provide a "up-to-date" account on this topic, through analysis of current literature and sharing our experiences during this pandemic.

Pyoderma gangrenosum successfully treated with golimumab: Case report and review of the literature.

Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis frequently related to chronic inflammatory bowel disease (IBD) often associated with exacerbation of intestinal disease and/or loss of treatment efficacy. However, in patients with comorbidities, such as diabetes, the diagnosis may be a challenge. Here, we report the case of a 68-year-old man with a history of ulcerative rectocolitis (URC), type II diabetes and arterial hypertension, who had been treated with infliximab and adalimumab in the past. In September 2017, patient developed an erythematous, infiltrated and painful lesion of the third distal part of his left leg, with ulcerative evolution, rapidly worsened despite a broad-spectrum antibiotic treatment had been introducted. A worsening of rectocolitis occurred simultaneously. In agreement with the gastroenterologists, patient started a new biological therapy with golimumab, and oral prednisone with slow tapering of steroid dosage following the improvement of both cutaneous and intestinal symptoms. Dermatologists should be aware about the risk of PG in patient suffering from IBDs, and consider this diagnosis in all patients affected by URC developing rapidly extending ulcerative skin lesion. Moreover, therapeutic choice should take into consideration the effectiveness of golimumab on the inflammatory background, which sustains both intestinal and skin disease in this type of patients.