Shedding Light on Novel Pathogenic and Therapeutic Aspects Related to Immune-Mediated Skin Diseases

Great advances in the understanding of the pathogenic mechanisms characterizing various immune-mediated skin diseases have been achieved. As a consequence, new potential therapeutic targets have been identified. This Special Issue proposes insights on various immune-mediated disorders, shedding light on peculiar pathogenic features and novel therapeutic aspects that could be of great interest. In common inflammatory skin disorders, including psoriasis and atopic dermatitis, whose pathogenic models have been mostly elucidated in the last two decades, the current research field is mostly oriented toward identifying novel treatment strategies or toward tailoring and personalizing treatment approaches

Dusky Red Swelling of the Penis in Association with Fever and Diarrhoea: A Quiz.

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Spotlight on dupilumab in the treatment of atopic dermatitis: Design, development, and potential place in therapy

Atopic dermatitis (AD) is among the most common inflammatory skin diseases in children and adults in industrialized countries. Up to one-third of adults (probably a smaller proportion in childhood) suffer from moderate-to-severe AD, whose recommended treatment is usually based on systemic therapies. The currently available therapeutics are limited, and AD management becomes challenging in most cases. Over the last few years, new advances in the understanding of AD pathogenic mechanisms and inflammatory pathways have led to the identification of specific therapeutic targets and new molecules have been tested. Dupilumab is a fully human monoclonal antibody directed against the IL-4 receptor α subunit that is able to block the signaling of both IL-4 and IL-13 and achieve rapid and significant improvements in adults with moderate-to-severe AD. Dupilumab is ready to inaugurate a long and promising biological target treatment option for Th2 cell-mediated atopic immune response that characterizes AD

Psoriasis: talking points from recent clinical trials

Psoriasis is a chronic inflammatory skin disease that includes a wide spectrum of clinical variants. The most common form of psoriasis is chronic plaque psoriasis, which manifests as well- demarked, erythematous, and scaly plaques. The pathogenic mechanisms underlying either plaque or pustular psoriasis overlap because of the central role of the interleukin-(IL-)23/ IL-17A axis in both conditions, though pustular psoriasis is characterized by a more prominent contribution of the innate immune compartment involving the IL-1 cytokine family [1]. Besides the development of antibodies targeting either solu-ble pathogenic cytokines or their receptor, the inhibition of the intracellular signaling induced by multiple cytokines and chemokines has been proposed as an alternative therapeutic strategy. Nowadays, the therapeutic paradigm for plaque psor-iasis includes topical, phototherapy, conventional systemic treatments, different classes of biological agents, and small molecules. Contrary to plaque psoriasis, only one biologic agent has received approval for the treatment of pustular psoriasis. The pipeline of plaque psoriasis consists of topical and systemic agents that showed promising results in phase II trials, as well as for pustular psoriasis, with one additional IL-36 receptor antagonist under investigation. This editorial aimed to collect and discuss clinical outcomes deriving from the most advanced trials testing promising agents, either topical or systemic. A narrative review for selected agents with a robust clinical trial program was performed

Urticaria associated with hyper-IgE in a patient with psoriasis undergoing treatment with efalizumab.

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Scanning the immunopathogenesis of psoriasis

Psoriasis is a chronic inflammatory skin disease, the immunologic model of which has been profoundly revised following recent advances in the understanding of its pathophysiology. In the current model, a crosstalk between keratinocytes, neutrophils, mast cells, T cells, and dendritic cells is thought to create inflammatory and pro-proliferative circuits mediated by chemokines and cytokines. Various triggers, including recently identified autoantigens, Toll-like receptor agonists, chemerin, and thymic stromal lymphopoietin may activate the pathogenic cascade resulting in enhanced production of pro-inflammatory and proliferation-inducing mediators such as interleukin (IL)-17, tumor necrosis factor (TNF)-α, IL-23, IL-22, interferon (IFN)-α, and IFN-γ by immune cells. Among these key cytokines lie therapeutic targets for currently approved antipsoriatic therapies. This review aims to provide a comprehensive overview on the immune-mediated mechanisms characterizing the current pathogenic model of psoriasis

Atopic Dermatitis in the Elderly Population

Acta DermatoVenereologica Atopic dermatitis is a common inflammatory disease with a chronic and relapsing course. Although considered a childhood disease, it is now evident that atopic dermatitis is also common in adulthood and in the elderly population. Atopic dermatitis typically manifests with bilateral and symmetrical eczematous lesions on the face, trunk and skin folds. Itch is invariably present and may be very severe, markedly affecting daily life and sleep. In older adults, atopic dermatitis may have a high level of impact on quality of life, frequently burdening an already complex comorbid situation. The full assessment of disease burden (localizations, itch severity, sleep alterations, impact on quality of life, disease history, comorbidities) is crucial to identify the most appropriate treatment. In many cases, moderate-to-severe atopic dermatitis in the elderly population can be successfully and safely treated with biological agents inhibiting the interleukin-4/-13 pathway, whereas the use of Janus kinase inhibitors may pose concerns about the safety profile

Complete Resolution of Erythrodermic Psoriasis in an HIV and HCV Patient Unresponsive to Antipsoriatic Treatments after Highly Active Antiretroviral Therapy (Ritonavir, Atazanavir, Emtricitabine, Tenofovir).

Background: Psoriasis is a chronic, inflammatory disease affecting 2–3% of the worldwide population, and it may worsen with HIV or be detected as HIV cutaneous manifestation. HIV-related psoriasis shows a severe and prolonged clinical course with more frequent exacerbations. The management of this condition is challenging because immunomodulating and immunosuppressant agents may have variable and partial efficacy, and therefore, antiretroviral treatment represents a potential adjunctive therapeutic option. Results: In the case we report, the HIV test was shown to be crucial for driving the therapeutic approach. Indeed, antiretroviral agents have been proven to be effective in the treatment of HIV+ psoriasis as first-line therapy. Conclusion: The HIV test should be considered in high-risk patients affected by severe psoriasis and resistant to conventional and biological treatments

AtopyReg®, the Prospective Italian Patient Registry for Moderate‐to‐Severe Atopic Dermatitis in Adults: Baseline Demographics, Disease Characteristics, Comorbidities, and Treatment History

Background and Objective AtopyReg® is a multicenter, prospective, observational, non-profit cohort study on moderate-tosevere atopic dermatitis in adults promoted in 2018 by the Italian Society of Dermatology and Venereology (SIDeMaST). We aimed to describe baseline demographics, disease characteristics, comorbidities, and therapeutic data of adult patients affected by moderate-to-severe atopic dermatitis. Methods Patients were selected based on the following inclusion criteria: age ≥ 18 years; Eczema Area and Severity Index score ≥ 16 or localization in visible or sensitive areas (face, neck, hands, or genitalia), or a Numeric Rating Scale itch score ≥ 7 or a Numeric Rating Scale sleep loss score ≥ 7, or a Dermatology Life Quality Index score ≥ 10. Demographic and clinical data at baseline were recorded and analyzed. Results A total of 1170 patients (male 51.1%; mean age: 44.7 years; range 18–90 years) were enrolled by 12 Italian Dermatology Units between January 2019 and November 2022. Skin lesions were eczematous in 83.2% of patients, the most involved site were the flexures (53.9%), face (50.9%), and neck (48.0%). Mean Eczema Area and Severity Index score was 22.3, mean Dermatology Life Quality Index value was 17.6, mean Patient Oriented Eczema Measure score was 13.1, and mean Numeric Rating Scale itch and sleep loss scores were 7.6 and 5.9, respectively. Previous systemic therapies were corticosteroids in 77.7% of patients, antihistamines in 50.3% of patients, and cyclosporine A in 42.6% of patients. Conclusions This baseline data analysis deriving from AtopyReg ® provides real-life evidence on patients with moderateto- severe atopic dermatitis in Italy confirming the high burden of atopic dermatitis with a significant impact on patients’ quality of life