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Molecular mechanisms of pruritus in prurigo nodularis.

ABSTRACT: Pruritus is the most common symptom of dermatological disorders, and prurigo nodularis (PN) is notorious for intractable and severe itching. Conventional treatments often yield disappointing outcomes, significantly affecting patients' quality of life and psychological well-being. The pathogenesis of PN is associated with a self-sustained "itch-scratch" vicious cycle. Recent investigations of PN-related itch have partially revealed the intricate interactions within the cutaneous neuroimmune network; however, the underlying mechanism remains undetermined. Itch mediators play a key role in pruritus amplification in PN and understanding their action mechanism will undoubtedly lead to the development of novel targeted antipruritic agents. In this review, we describe a series of pruritogens and receptors involved in mediating itching in PN, including cytokines, neuropeptides, extracellular matrix proteins, vasculogenic substances, ion channels, and intracellular signaling pathways. Moreover, we provide a prospective outlook on potential therapies based on existing findings.

SUBMITTER: Shao Y

PROVIDER: S-EPMC10701428 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Molecular mechanisms of pruritus in prurigo nodularis.

Shao Yixin Y Wang Duoqin D Zhu Yiqi Y Xiao Zijing Z Jin Taiyu T Peng Lisi L Shen Yanyun Y Tang Hui H

Frontiers in immunology 20231123

Pruritus is the most common symptom of dermatological disorders, and prurigo nodularis (PN) is notorious for intractable and severe itching. Conventional treatments often yield disappointing outcomes, significantly affecting patients' quality of life and psychological well-being. The pathogenesis of PN is associated with a self-sustained "itch-scratch" vicious cycle. Recent investigations of PN-related itch have partially revealed the intricate interactions within the cutaneous neuroimmune netwo ...[more]

PMID: 38077377

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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:ImportanceBecause of a paucity of qualitative research on prurigo nodularis (PN), the symptoms and impacts of PN that are most important to patients are poorly understood.ObjectiveTo explore patients' perspectives on their PN symptoms and to understand the impacts of the condition.Design, setting, and participantsOne-on-one qualitative telephone interviews were held with English-speaking US adults aged 18 years or older with a confirmed diagnosis of PN, severe pruritus, and moderate to severe sleep disturbance. Participants were recruited via patient associations, patient panels, and social media posts. Interviews took place between September 10, 2020, and March 16, 2021.Main outcomes and measuresThe main symptoms of PN and their impacts on quality of life were identified by content analysis of deidentified interview transcripts.ResultsA total of 21 adults with PN (mean [SD] age, 53.1 [11.8] years; 15 [71%] female; 2 African American or Black patients [10%], 1 Asian patient [5%], and 18 White patients [86%]; of these, 1 patient [ 5%] had Hispanic or Latino ethnicity) participated in the interviews. All participants reported itch, pain associated with PN, bleeding or scabbing, and dry skin. Other frequently reported symptoms included lumps or bumps (95%), having a crust on the skin (95%), burning (90%), stinging (90%), lesions or sores (86%), skin discoloration (86%), and raw skin (81%). Of the 17 participants who indicated what their worst symptoms were, 15 (88%) identified itching as the worst or 1 of the worst symptoms. The most frequently reported impacts of PN for quality of life were changes in sleep (100%), daily life (100%), feelings or mood (95%), relationships (95%), social life (81%), and work or school (71%). Overall, the worst impact of PN was its association with impaired feelings or mood.Conclusions and relevanceThis qualitative study suggests the importance of itching, sleep disturbance, and other symptoms and impacts of PN. This information can be used to guide end point selection in clinical trials and to inform patient-centric decision-making in clinical practice.

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Molecular mechanisms of pruritus in prurigo nodularis.

Publications

Molecular mechanisms of pruritus in prurigo nodularis.

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