Myeloid dendritic cells are increased in the lesional skin and associated with pruritus in patients with prurigo nodularis
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SUBMITTER: Liu T
PROVIDER: S-EPMC9921813 | biostudies-literature | 2023 Feb
REPOSITORIES: biostudies-literature
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Project description: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.
| S-EPMC10701428 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2022-10-31 | GSE210854 | GEO
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.
| S-EPMC10796623 | biostudies-literature
Project description:Prurigo nodularis (PN) is a chronic inflammatory skin disease characterized by symmetrically distributed, intensely pruritic nodules of unknown etiology and unmet therapeutic need. The lack of approved therapies and the limited efficacy of off-label treatments reflect the current poor understanding of its pathogenesis. We aimed to comprehensively characterize the phenotypic variation of CD3+ T cells and asses cell-specific gene expression in the lesional skin of patients with PN versus in patients with atopic dermatitis (AD) and in healthy controls (HC). To this end, single-cell RNA sequencing (scRNA-Seq) using 10x Genomics was carried out to compare CD3+ T cells transcriptomic heterogeneity between lesional samples of PN (n=6), AD (n=5) and HC (n=5).
2023-07-08 | GSE213849 | GEO
Project description:IntroductionValidated patient report tools for quantifying patient experiences of itch in prurigo nodularis (PN) are limited. This study aimed to evaluate the validity of the 11-point peak pruritus numerical rating scale (PP NRS) as a single-item patient-reported outcome (PRO) measure for assessing itch severity in PN.MethodsContent validity of the PP NRS was evaluated through qualitative interviews with adults with PN. The PP NRS was then psychometrically evaluated using data from a placebo-controlled trial of nemolizumab in adults with PN, during which patients completed the PP NRS daily. Meaningful within-patient change was estimated from the qualitative interviews and by anchor- and distribution-based analyses of trial data.ResultsThe interview participants (N = 21) all understood the PP NRS and reported itch as their worst symptom overall. The PP NRS showed good test-retest reliability and demonstrated convergent validity and known-groups validity. PP NRS scores improved more in patients classified as "improved" on other clinical outcome measures than in those classified as "worsened/unchanged". Triangulation of the different estimates identified a 2- to 5-point decrease in PP NRS score as a meaningful within-patient change threshold.ConclusionThe PP NRS is a content-valid and reliable PRO measure for quantifying itch severity in adults with PN in clinical trials.Trial registration numberNCT03181503.
| S-EPMC10539229 | biostudies-literature
Project description:Prurigo nodualris (PN) is a chronic condition with highly pruritic, hyperkeratotic papules or nodules arising in the setting of chronic pruritus. While PN may serve as a phenotypic presentation of several underlying conditions such as atopic dermatitis, chronic kidney disease-related pruritus, and neurological diseases, it represents a distinct clinical entity that may persist despite the removal of the underlying cause, if one is identified. Neuronal proliferation, eosinophils, mast cells, and small-fiber neuropathy play a role in the production of pruritus in PN, although the exact mechanism has not yet been established. Identifying an underlying cause, if present, is essential to prevent recurrence of PN. Due to often present comorbidities, treatment is typically multimodal with utilization of topical and systemic therapies. We performed a PubMed/MEDLINE search for PN and present a review of recent developments in the treatment of PN. Treatment typically relies on the use of topical or intralesional steroids, though more severe or recalcitrant cases often necessitate the use of phototherapy or systemic immunosuppressives. Thalidomide and lenalidomide can both be used in severe cases; however, their toxicity profile makes them less favorable. Opioid receptor antagonists and neurokinin-1 receptor antagonists represent two novel families of therapeutic agents which may effectively treat PN with a lower toxicity profile than thalidomide or lenalidomide.
| S-EPMC6400231 | biostudies-literature
Project description:ImportanceThere is an unmet need for psychometrically sound instruments to measure pruritus associated with prurigo nodularis (PN).ObjectiveTo evaluate the psychometric properties of the itch numeric rating scale (itch NRS), both the Worst Itch Numeric Rating Scale (WI-NRS) and the Average Itch Numeric Rating Scale (AI-NRS).Design, setting, and participantsThis secondary analysis is based on a secondary end point of a phase 2 randomized clinical trial of serlopitant for treatment of pruritus associated with PN. This randomized, double-blind, placebo-controlled study was conducted at 15 sites in Germany. Eligible patients were aged 18 to 80 years and had generalized PN for more than 6 weeks that was refractory to previous antipruritic therapies. Patients were required to have a visual analog scale itch score of 7 or higher at screening. Data were collected from July 2014 to June 2016 and analyzed from June 2016 to January 2017.Main outcomes and measuresThe itch NRS (AI-NRS and WI-NRS) was correlated together with the following measures: the electronic verbal rating scale (eVRS) for itch self-categorization, average itch visual analog scale (AI-VAS), worst itch visual analog scale (WI-VAS), the pruritus-specific quality-of-life rating instrument ItchyQoL, Dermatology Life Quality Index (DLQI), and Prurigo Activity and Severity Score (items 7b and 7a: percentage healed prurigo lesions and percentage of prurigo lesions with excoriations).ResultsThere were 123 participants in this study; the mean (SD) age of participants was 57.3 (11.58) years, and 58 (47.2%) were male. Strong associations (r ≥ 0.5) were observed between itch NRS items (WI-NRS and AI-NRS) and AI-VAS (24 hours) at weeks 2, 4, and 8 (r = 0.72-0.90; P < .001). Similar strong associations were also observed between itch NRS items and WI-VAS (24 hours) and eVRS for itch severity across weeks 2, 4, and 8 (r = 0.65-0.92; all P < .001). Strong correlations were seen between change scores for WI-NRS and WI-VAS and AI-VAS (r = 0.76 and 0.70, respectively; both P < .001). Similar findings were seen for AI-NRS, where correlations between change scores for WI-VAS and AI-VAS were 0.71 and 0.72, respectively (both P < .001). Analyses for the itch NRS items also showed that test-retest reliability was acceptable and provided evidence of acceptable convergent validity based on the eVRS and visit verbal rating score for itch self-categorization, ItchyQoL, and DLQI.Conclusions and relevanceResults from this secondary analysis show that the itch NRS items WI-NRS and AI-NRS have good psychometric properties for pruritus associated with PN and should be considered acceptable tools for assessing pruritus in future clinical trials of PN.Trial registrationClinicalTrials.gov Identifier: NCT02196324.
| S-EPMC7495327 | biostudies-literature
Project description:Prurigo nodularis is a debilitating skin condition that is characterized by chronic itch and a prolonged scratching behavior. Little is known of the underlying molecular mechanisms that initiate and maintain the desease. Therefore, we analyzed gene expression in prurigo patients and matched healthy controls.
2022-10-31 | GSE210829 | GEO
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.
| S-EPMC10512162 | biostudies-literature