Dataset Information

Chronic Nodular Prurigo: An Update on the Pathogenesis and Treatment.

ABSTRACT: Chronic nodular prurigo (CNPG) is a recalcitrant chronic itchy disorder that affects the quality of life. It can be triggered by multiple etiologies, such as atopic dermatitis, diabetes, and chronic renal diseases. The mechanisms of CNPG are complicated and involved the interaction of the cutaneous, immune, and nervous systems. Diverse immune cells, including eosinophils, neutrophils, T cells, macrophages, and mast cells infiltrated the lesional skin of CNPG, which initiated the inflammatory cytokines and pruritogens release. In addition, the interaction between the immune cells and activated peripheral sensory nerve fibers by neurotransmitters caused neuroinflammation in the skin and intractable itch. This itch-scratch vicious cycle of CNPG results in disease exacerbation. CNPG is difficult to treat with traditional therapies. Recently, great advances have been made in the pathophysiology of both inflammation and pruritus transmission in CNPG. In this review, we summarize the updated mechanisms and novel therapies for CNPG.

SUBMITTER: Wong LS

PROVIDER: S-EPMC9604302 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Chronic Nodular Prurigo: An Update on the Pathogenesis and Treatment.

Wong Lai-San LS Yen Yu-Ta YT

International journal of molecular sciences 20221016 20

Chronic nodular prurigo (CNPG) is a recalcitrant chronic itchy disorder that affects the quality of life. It can be triggered by multiple etiologies, such as atopic dermatitis, diabetes, and chronic renal diseases. The mechanisms of CNPG are complicated and involved the interaction of the cutaneous, immune, and nervous systems. Diverse immune cells, including eosinophils, neutrophils, T cells, macrophages, and mast cells infiltrated the lesional skin of CNPG, which initiated the inflammatory cyt ...[more]

PMID: 36293248

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Project description:Chronic prurigo (CPG) is a neuroinflammatory, fibrotic dermatosis that is defined by the presence of chronic pruritus (itch lasting longer than 6 weeks), scratch-associated pruriginous skin lesions and history of repeated scratching. Patients with CPG experience a significant psychological burden and a notable impairment in their quality of life. Chronic prurigo of nodular type (CNPG; synonym: prurigo nodularis) represents the most common subtype of CPG. As CNPG is representative for all CPG subtypes, we refer in this review to both CNPG and CPG. We provide an overview of the clinical characteristics and assessment of CPG, the burden of disease and the underlying pathophysiology including associated therapeutic targets. The information provided results from a PubMed search for the latest publications and a database search for current clinical trials (ClinicalTrials.gov, EU Clinical Trials Register [European Medicines Agency]; using the following terms or combinations of terms: 'chronic prurigo', 'prurigo', 'prurigo nodularis', 'pathophysiology', 'therapy', 'biologics', 'treatment'). Dupilumab is the first authorized systemic therapy by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) for CNPG to date. Topical and systemic agents that are currently under investigation in clinical randomized, placebo-controlled phase II and III trials such as biologics (e.g., nemolizumab, vixarelimab/KPL-716, barzolvolimab/CDX-0159), small molecules (ruxolitinib cream, povorcitinib/INCB054707, abrocitinib) and the opioid modulator nalbuphine are highlighted. In the last past 15 years, several milestones have been reached regarding the disease understanding of CPG such as first transcriptomic analysis, first terminology, first guideline, and first therapy approval in 2022, which contributed to improved medical care of affected patients. The broad range of identified targets, current case observations and initiated trials offers the possibility of more drug approvals in the near future.

Project description:IntroductionBullous pemphigoid (BP) and prurigo nodularis (PN) are chronic pruritic skin diseases that severely impact patients' quality of life. Despite the widespread attention these two diseases have garnered within the dermatological field, the specific pathogenesis, particularly the molecular mechanisms underlying the pruritus, remains largely unclear. Limited clinical sequencing studies focusing on BP and PN have hindered the identification of pathological mechanisms and the exploration of effective treatment strategies.MethodsTo address this gap, we collected a total of 23 peripheral blood mononuclear cell samples from BP and PN patients, as well as healthy controls, and performed RNA sequencing analysis. By integrating bioinformatics and machine learning techniques, we aimed to uncover the shared immune regulatory networks and pruritus-related mechanisms between BP and PN.ResultsOur study identified 161 differentially expressed genes shared between BP and PN, which were primarily enriched in immune activation and neural pathways, providing crucial molecular insights into the pruritus-related mechanisms of both diseases. Furthermore, using the machine learning algorithms of support vector machines and random forest, we pinpoint 7 crucial genes shared between the BP and PN databases. Among these, IL-27 emerged as a potential pivotal gene, as its mRNA expression levels strongly correlated with clinical parameters including pruritus scores, immunoglobulin E levels, and eosinophil counts. Validation experiments conducted on clinical samples from an additional 22 participants confirmed the upregulation of IL-27 expression in both BP and PN lesions.DiscussionThis study is the first to unveil the shared inflammatory and immune pathways common to BP and PN, highlighting the critical role of IL-27 in the pathogenesis of these conditions. Our findings not only enhance the understanding of the intricate relationship between BP and PN, but also provide a foundation for the development of novel therapeutic strategies targeting these two dermatological conditions.

Dataset Information

Chronic Nodular Prurigo: An Update on the Pathogenesis and Treatment.

Publications

Chronic Nodular Prurigo: An Update on the Pathogenesis and Treatment.

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