Prurigo Nodularis Research Articles

Prevalence of prurigo nodularis in the United States

Prevalence of prurigo nodularis in the United States

Is Dupilumab a chance for patients with moderate to severe atopic dermatitis? Literature review

Introduction: Atopic dermatitis is an inflammatory disease which can significantly affect quality of life of patients. Especially severe forms of this disease are challenging to treat and for a long time forms of treatment have been limited. Because of that- it is crucial to find new ways of treatment which can be registered and impove moderate and severe dermatitis.
 Aim of study: Fundament purpose of this literature review is focusing on effectiveness, safety, side effects or different potential medical applications of Dupilumab. The main question, which is formulated in the title- is Dupilumab a chance for patients with moderate to severe atopic dermatitis?
 State of knowledge: Nowadays Dupilumab is well known drug and a lot of trials and analysis focus on efficacy, safety in treatment of moderate and severe dermatitis. The development of Dupilumab and different potential, clinical applications is also a chance for other groups of patients- for example patients with asthma, chronic rhinosinusitis with nasal polyps, eosinophilic esophagitis, prurigo nodularis.
 Conclusion: Dupilumab is definitely a relevant and essential element of treatment therapy for patients with moderate to severe atopic dermatitis. There were many analysis and researches which confirmed effectiveness, safety level and described Dupilumab impact on many different parameteres and scales focused on symptoms and life quality of patients during treatment with Dupilumab.

Prurigo nodularis: new insights into pathogenesis andnovel therapeutics.

Prurigo nodularis (PN) is an inflammatory skin condition characterized by intensely pruritic nodules on the skin. Patients with PN suffer from an intractable itch-scratch cycle leading to impaired sleep, psychosocial distress and a significant disruption in quality of life. The pathogenesis of PN is associated with immune and neural dysregulation, mediated by inflammatory cytokines [such as interleukin (IL)-4, -13, -17, -22 and -31] and neuropeptides (such as substance P and calcitonin gene-related peptide). There is a role for type 2 inflammation in PN in addition to T-helper (Th)17 and Th22-mediated inflammation. The neuroimmune feedback loop in PN involves neuropeptides released from nerve fibres that cause vasodilation and further recruitment of inflammatory cells. Inflammatory cells, particularly mast cells and eosinophils, degranulate and release neurotoxins, as well as nerve growth factor, which may contribute to the neuronal hyperplasia seen in the dermis of patients with PN and neural sensitization. Recent studies have also indicated underlying genetic susceptibility to PN in addition to environmental factors, the existence of various disease endotypes centred around degrees of type 2 inflammation or underlying myelopathy or spinal disc disease, and significant race and ethnicity-based differences, with African Americans having densely fibrotic skin lesions. Dupilumab became the first US Food and Drug Administration-approved therapeutic for PN, and there are several other agents currently in development. The anti-IL-31 receptor A inhibitor nemolizumab is in late-stage development with positive phase III data reported. In addition, the oral Janus kinase (JAK) 1 inhibitors, abrocitinib and povorcitinib, are in phase II trials while a topical JAK1/2 inhibitor, ruxolitinib, is in phase III studies.

Estimating meaningful change thresholds for Skin Pain-Numeric Rating Scale, Sleep-Numeric Rating Scale and Dermatology Life Quality Index in patients with prurigo nodularis.

Prurigo nodularis (PN) is characterized by intensely itchy nodules/lesions and skin pain, which can have a substantial impact on health-related quality of life (HRQoL). Treatment benefits on such symptoms and impacts are best assessed in trials using patient-reported outcome (PROs) instruments such as Skin Pain Numerical Rating Scale (NRS), Sleep-NRS and Dermatology Life Quality Index (DLQI). However, no guidance exists for interpreting meaningful changes in scores using these PROs in patients with PN. The main objective was to derive within-patient (responder definition) and between-group improvement thresholds for interpreting Skin Pain-NRS, Sleep-NRS and DLQI total scores in patients with PN. The measurement properties of the three PROs were also evaluated. Intention-to-treat (ITT), blinded and pooled data were used from the Phase 3 PRIME (NCT04183335) and PRIME2 (NCT04202679) studies evaluating the efficacy of dupilumab in adult patients with PN. Anchor- and distribution-based methods were applied to derive responder definition and between-group thresholds for Skin Pain-NRS, Sleep-NRS and DLQI. Data were additionally used to examine the instrument measurement properties, including reliability, validity and responsiveness. A total of 311 patients (mean age 49.5 years, 65.3% female) were included in the pooled ITT population. The within-patient improvement threshold for Skin Pain-NRS was estimated as 4.0 points, 2.0 points for Sleep-NRS and 9.0 points for DLQI total score. A 1.5-point improvement in Skin Pain-NRS scores, 1.0-point in Sleep-NRS and 4.0-point in DLQI indicated a between-group meaningful change. Adequate to good psychometric properties were demonstrated for all three instruments. The results of this study can aid interpretation of Skin Pain-NRS, Sleep-NRS and DLQI scores in patients with PN in both clinical trials and clinical practice to better understand and treat PN-related skin pain and the impact of PN on sleep quality and HRQoL.

564 - Conjunctivitis adverse events in dupilumab clinical trials

Abstract Introduction Dupilumab inhibits signaling of IL-4 and IL-13, key drivers of Type 2 inflammatory diseases such as atopic dermatitis (AD), asthma, chronic rhinosinusitis with nasal polyposis (CRSwNP), eosinophilic esophagitis (EoE), prurigo nodularis (PN), and Chronic Spontaneous Urticaria (CSU).1,2 Adults with AD have a significant and disease severity-dependent increased risk of developing ocular surface diseases, including conjunctivitis and keratitis, compared with the general population.3 In randomized placebo-controlled trials of dupilumab in patients with moderate-to-severe AD, more conjunctivitis events were reported in patients who received dupilumab treatment than in placebo-treated patients.4,5 Objective This analysis reviewed the incidence, severity, and resolution of conjunctivitis adverse events (AEs) in patients from clinical trials evaluating dupilumab in AD, asthma, CRSwNP, EoE, PN, and CSU. Methods “Conjunctivitis” refers to the group of MedDRA Preferred Terms (PTs) that include the term ‘conjunctivitis’, namely conjunctivitis, allergic conjunctivitis, bacterial conjunctivitis, viral conjunctivitis, adenoviral conjunctivitis, and atopic keratoconjunctivitis. All cases of conjunctivitis were included regardless of etiology (including blepharoconjunctivitis, which was coded as the MedDRA PT conjunctivitis, and excluding blepharitis in the absence of conjunctivitis. This analysis excludes events of keratitis. Randomized, double-blinded, placebo-controlled trials included in this analysis were: Liberty AD Solo 1, Liberty AD Solo 2, Liberty AD Chronos, LIBERTY AD ADOL, LIBERTY AD PEDS, LIBERTY AD PRESCHOOL Part B (AD); Liberty Asthma Quest, Liberty Asthma Venture (asthma); Liberty NP Sinus-24, Liberty NP Sinus-52 (CRSwNP); Liberty EoE Treet (EoE); Liberty PN Prime, Liberty-PN Prime2 (PN); and Liberty-CSU Cupid Part A (CSU). Results Overall conjunctivitis incidence was higher in patients receiving dupilumab vs placebo in all randomized AD trials, with 7.9% to 19.4% of adult dupilumab-treated patients and 4.8% to 14.8% of dupilumab-treated patients aged 6 months to <18 years experiencing conjunctivitis events. In contrast, conjunctivitis rates were <5% and similar between dupilumab and placebo in the asthma, CRSwNP, EoE, PN, and CSU trials. Most conjunctivitis cases observed in adult patients with AD receiving dupilumab treatment were mild to moderate in severity, with severe conjunctivitis being reported at rates of ≤0.6%. A majority of all conjunctivitis cases in dupilumab-treated adults with AD were resolved during the treatment period. Conclusions Overall conjunctivitis events were more frequent in dupilumab-treated vs placebo-receiving patients in AD trials across ages, whereas rates were low and similar between dupilumab and placebo groups in the asthma, CRSwNP, EoE, PN, and CSU trials. Most conjunctivitis cases observed in adult patients with AD receiving dupilumab treatment were mild to moderate in severity and resolved by the end of the study period. Current evidence suggests that conjunctivitis associated with dupilumab occurs predominantly in patients with AD. It is possible that pre-existing ocular disorders and a dupilumab–AD disease-specific interaction may be responsible for this increased incidence in dupilumab-treated patients with AD.

512 - Dupilumab treatment improves satisfaction in patients with prurigo nodularis who did not achieve the multicomponent endpoint: analysis from LIBERTY-PN PRIME and PRIME2

Abstract Introduction Patients with prurigo nodularis (PN) often report high disease burden with substantial impact on quality of life. Patient Global Impression of Change (PGIC) and Severity (PGIS) are patient self-assessment measures that quantify their experience of disease during treatment. Dupilumab has recently been approved as the first systemic treatment for PN in the US and Europe. Objectives To evaluate patient-reported global impression of disease severity improvement in dupilumab-treated patients with PN during the LIBERTY-PN PRIME and PRIME 2 trials. Materials & Methods PRIME and PRIME2 were randomized, double-blind, multicenter, parallel-group, 24-week, phase 3 trials in adults with PN with ≥20 nodules and severe itch, inadequately controlled with topical prescription therapies or for whom these are inadvisable. Patients received 300 mg dupilumab subcutaneously (600 mg loading dose; n = 153) or matched placebo (n = 158) every 2 weeks. In this analysis, data from the two studies were pooled. Patient satisfaction was assessed in the overall placebo group, overall dupilumab-treated group, and those treated with dupilumab who did not achieve the stringent multicomponent endpoint (n = 99) of ≥4-point improvement from baseline in Worst Itch Numerical Rating Scale (WI-NRS, range: 0–10) and an Investigator’s Global Assessment PN Stage (IGA PN-S, score range: 0–4) score 0 or 1 (clear or almost clear; ≤5 nodules) at Week (W) 24. Endpoints include proportion of patients achieving: PGIC (range: 0–6) scores of 0 or 1 (very much better or moderately better) at W12, and W24; and PGIS (range: 1–4) score of 1 or 2 (none or mild) at baseline, W12, and W24. Safety was also assessed. Results Baseline demographic and clinical characteristics were generally similar between groups. In the overall dupilumab and placebo groups, baseline mean (SD) WI-NRS scores were 8.6 (0.9) and 8.4 (1.1), respectively; 32.7% and 34.2% had an IGA PN-S score of 4 (remaining patients had IGA PN-S 3); and mean (SD) PGIS scores were 3.7 (0.5) and 3.7 (0.5) respectively. In dupilumab multicomponent endpoint non-responders, mean (SD) WI-NRS score was 8.6 (0.9). 35.4% and 64.6% had an IGA PN-S score of 4 and 3 respectively; and mean (SD) PGIS score was 3.7 (0.5). At W12, 68.0% vs 38.0% (P < 0.0001 vs placebo) of dupilumab-treated vs placebo-receiving patients achieved PGIC 0 or 1, while 55.6% of dupilumab multicomponent non-responders achieved this endpoint (P = 0.0099 vs placebo). At W24, this increased to 74.5% vs 32.9% (P < 0.0001 vs placebo) of dupilumab-treated vs placebo-receiving patients achieving PGIC 0 or 1, and 61.6% of multicomponent non-achievers (P < 0.0001 vs placebo). At W12, 51.6% vs 22.2% (P < 0.0001 vs placebo) of dupilumab-treated vs placebo-receiving patients achieved PGIS 1 or 2, while 40.4% of multicomponent non-responders achieved the endpoint (P = 0.0027 vs placebo). At W24, 61.4% vs 24.1% (P < 0.0001 vs placebo) of dupilumab-treated vs placebo-receiving patients achieved PGIS 1 or 2, while 44.4% of multicomponent non-responders achieved the endpoint (P = 0.0025 vs placebo). Safety findings were consistent with the known dupilumab safety profile. Conclusions While not all patients achieved the stringent multicomponent endpoint within the 24-week treatment period during PRIME and PRIME 2 trials, around half of the dupilumab-treated patients still reported significantly more improvement in disease severity and satisfaction with therapy. Overall safety was consistent with the known dupilumab safety profile.

510 - Dupilumab is efficacious in patients with prurigo nodularis regardless of stable use of topical corticosteroids and topical calcineurin inhibitors: pooled results from two phase 3 trials (LIBERTY-PN PRIME and PRIME2)

Abstract Introduction Prurigo nodularis (PN) is a chronic inflammatory skin condition characterized by severely itchy skin nodules, which substantially affects quality of life. Although topical treatments are frequently prescribed, these therapies are limited by insufficient demonstrated evidence for efficacy, and/or associated side effects. Objectives This study reports the effect of dupilumab on pruritus, skin lesions, and quality of life in patients with PN, with or without stable use of topical corticosteroids (TCS) and/or topical calcineurin inhibitors (TCI), in an analysis of pooled data from two phase 3 trials. Materials & Methods LIBERTY-PN PRIME (NCT04183335) and PRIME2 (NCT04202679) were two randomized, double-blind, placebo-controlled, 24-week studies. Adults with PN inadequately controlled by topical prescription therapies, or for whom those therapies are inadvisable, were randomized 1:1 to dupilumab 300 mg every 2 weeks or matched placebo. “Stable use” was defined as maintaining the same medicine (low-to-medium potency TCS and/or TCI) during the study, with the same frequency of treatment (once or twice daily) as from 2 weeks prior to screening. Efficacy was assessed from baseline to Week 24 through the Worst Itch Numerical Rating Scale (WI-NRS; scored 0–10; high scores represent a poorer outcome), and the Investigator’s Global Assessment for PN-Stage score (IGA PN-S; scored 0–4; high scores represent a poorer outcome). Impact on Health-Related Quality of Life (HRQoL) was assessed through the Dermatology Life Quality Index questionnaire (DLQI; 10 questions scored 0–3 with a maximum score of 30; high scores represent poorer HRQoL). Results 311 patients were randomized (dupilumab/placebo n = 153/158), including 182 patients with stable use of TCI/TCS (dupilumab/placebo N = 91/91) and 129 patients without (dupilumab/placebo N = 62/67). Baseline demographics and disease characteristics were well balanced in both subgroups. At Week 24, significantly more patients treated with dupilumab with or without stable use of TCI/TCS achieved a ≥ 4-point improvement in WI-NRS (59.3%/58.1%) vs placebo (13.2%/26.9% [nominal P < 0.0001/P < 0.0001]). The proportion of patients achieving an IGA PN-S score of 0 or 1 at Week 24 was also significantly higher in the dupilumab group for patients with or without stable use of TCI/TCS (48.4%/43.5%), vs placebo (11.0%/25.4% [nominal P < 0.0001/P = 0.0319]). The positive impact of dupilumab treatment on HRQoL was greater, for patients with and without a stable use of TCI/TCS vs placebo, as suggested by the mean change from baseline in DLQI at Week 24 (−12.9/−11.9 vs −5.5/−7.1 [nominal P < 0.0001/P < 0.0001], respectively). Although the placebo response was higher for patients without stable use of TCI/TCS, the effect of dupilumab treatment was comparable in the two subgroups. Treatment-emergent adverse events (TEAEs) occurred with similar rates in dupilumab-treated patients with or without stable use of TCI/TCS (59.3%/60.7%), compared with placebo (53.3%/47.8%). Patients with or without stable use of TCI/TCS had similar rates of severe TEAEs in the dupilumab groups (2.2%/4.9%) and placebo groups (3.3%/4.5%). Conclusion Dupilumab treatment improves itch, skin lesions, and quality of life in patients with PN, with an acceptable safety profile, with little to no influence from concomitant treatment with topical therapies (TCI/TCS).

506 - Dupilumab is efficacious in patients with prurigo nodularis regardless of history of atopic comorbidities: pooled results from two phase 3 trials (LIBERTY-PN PRIME and PRIME2)

Abstract Introduction Prurigo nodularis (PN) is a chronic inflammatory skin condition characterized by severely itchy skin nodules. Nearly half of affected adult patients have a history of (or current) atopic comorbidity, such as atopic dermatitis (AD). Objective To report the efficacy and safety of dupilumab in patients with PN with or without history of atopic comorbidities, in a pre-specified analysis of pooled data from two phase 3 trials. Method In the randomized, double-blind, placebo-controlled, 24-week studies, LIBERTY-PN PRIME (NCT04183335) and PRIME2 (NCT04202679), adults with PN inadequately controlled by topical prescription therapies, were randomized 1:1 to dupilumab 300 mg every 2 weeks or matched placebo. Atopic patients were defined as patients with a physician-documented history, or current diagnosis, of at least one of the following atopic comorbidities: AD, allergic rhinitis/rhinoconjunctivitis, asthma, or food allergy. Efficacy was assessed from baseline to Week 24 through the Worst Itch Numerical Rating Scale (WI-NRS; 0–10), and the Investigator’s Global Assessment for PN-Stage score (IGA PN-S; 0–4). Results 311 patients were randomized (dupilumab n=153, atopic/non-atopic N=67/86; placebo n=158, atopic/non-atopic N=68/90). At Week 24, significantly more atopic and non-atopic dupilumab-treated patients achieved a ≥4-point improvement in WI-NRS (58.2%/59.3%), and an IGA PN-S score of 0 or 1 (52.2%/41.9%) vs placebo (20.6%/17.8% [nominal P<0.0001/P<0.0001] and 16.2%/17.8% [nominal P<0.0001/P=0.0005], respectively). The proportion of patients achieving concomitant ≥4-point improvement in WI-NRS and IGA PN-S score of 0 or 1 was higher for both dupilumab-treated atopic and non-atopic patients (37.3%/33.7%) vs placebo (7.4%/10.0% [nominal P=0.0057/P<0.007]). Overall safety was consistent with the known dupilumab safety profile, with no remarkable differences between atopic and non-atopic patients. Conclusion Dupilumab treatment improves itch and skin lesions in PN patients with and without a history of atopic comorbidities, indicating that underlying type 2 inflammation is present in patients with PN regardless of their history of atopic comorbidities.

Dupilumab for Treatment of Prurigo Nodularis: Real-Life Effectiveness for up to 84 Weeks

(1) Background: Prurigo nodularis (PN) is a persistent and inflammatory dermatological condition characterized by chronic itching and the formation of hardened nodules, significantly impacting the affected individuals’ quality of life and psychological well-being. The management of PN poses challenges due to the limited efficacy and undesirable side effects associated with current interventions. (2) Methods: This article examines sixteen patients affected by PN treated with dupilumab, a fully human monoclonal antibody targeting interleukin IL-4 and IL-13 signaling. This involves a retrospective descriptive statistical analysis. (3) Results and (4) Conclusions: In all patients, dupilumab proves to be an effective drug in achieving disease clearance, as indicated by all the parameters considered as assessed by both physicians and patients at each evaluation point (Week 6, Week 16, Week 32, Week 52, Week 68, and Week 84), in comparison to the initial baseline.

Staphylococcus aureus proteases trigger eosinophil-mediated skin inflammation

Staphylococcus aureus skin colonization and eosinophil infiltration are associated with many inflammatory skin disorders, including atopic dermatitis, bullous pemphigoid, Netherton's syndrome, and prurigo nodularis. However, whether there is a relationship between S. aureus and eosinophils and how this interaction influences skin inflammation is largely undefined. We show in a preclinical mouse model that S. aureus epicutaneous exposure induced eosinophil-recruiting chemokines and eosinophil infiltration into the skin. Remarkably, we found that eosinophils had a comparable contribution to the skin inflammation as T cells, in a manner dependent on eosinophil-derived IL-17A and IL-17F production. Importantly, IL-36R signaling induced CCL7-mediated eosinophil recruitment to the inflamed skin. Last, S. aureus proteases induced IL-36α expression in keratinocytes, which promoted infiltration of IL-17-producing eosinophils. Collectively, we uncovered a mechanism for S. aureus proteases to trigger eosinophil-mediated skin inflammation, which has implications in the pathogenesis of inflammatory skin diseases.

New insight into prurigo nodularis: Proadrenomedullin N-terminal 20 peptide mediates mouse mast cell activation via Mrgprb2.

Prurigo nodularis (PN) is a chronic inflammatory skin disorder that is characterized by extremely itchy nodules. Proadrenomedullin N-terminal 20 (PAMP) activates mast cell degranulation via Mas-related G protein-coupled receptor X2 (MRGPRX2), which is associated with pruritus in allergic contact dermatitis. However, the mechanisms underlying the action of PAMP and MRGPRX2 in PN remain unclear. To determine the role of PAMP-induced mast cell activation via MRGPRX2 (mouse homologous Mrgprb2) in PN. The expression of PAMP and the number of MRGPRX2-expressing mast cells in the skin biopsies of patients with PN, atopic dermatitis (AD), and healthy participants were analyzed using immunohistochemistry and immunofluorescence, respectively. The biphasic response of PAMP9-20 mediated by Mrgprb2 in mouse peritoneal mast cells (PMC) was validated in vitro using qRT-PCR, ELISA, flow cytometry, and siRNA techniques. PAMP expression and the number of MRGPRX2+ mast cells in lesional PN skin, but not in AD, were elevated compared to healthy skin. PAMP9-20 mediates the immediate and delayed phase responses of PMC, such as degranulation, histamine and β-hexosaminidase release, and secretion of inflammatory factors such as CCL2, TNF-α, and GM-CSF. These effects were inhibited when Mrgprb2 expression was silenced. Silencing Mrgprb2 did not affect the biphasic response of PMC that was induced by IgE-FcεRI activation. The results show that PAMP mediates mouse mast cell activation via Mrgprb2, which may be involved in the pathogenesis of PN. The PAMP/ Mrgprb2 pathway, independent of classical IgE signaling, could be developed as a candidate drug target for treating PN.

Baseline eosinophil level may be a predictive indicator for the effectiveness of dupilumab in patients with prurigo nodularis: A single-center, real-world prospective study

Baseline eosinophil level may be a predictive indicator for the effectiveness of dupilumab in patients with prurigo nodularis: A single-center, real-world prospective study

Clinical Characteristics and Treatment Outcomes of Prurigo Nodularis: A Retrospective Study.

Prurigo nodularis (PN) is a complex chronic skin disease characterized by severe pruritic nodules. PN is often associated with mental health disorders and chronic medical comorbidities. Until recently, PN treatment has been challenging and difficult. This study aims to describe the demographic, clinical characteristics, and comorbidities associated with PN. Also, we aim to describe the effectiveness of systemic therapies, including methotrexate, cyclosporine, and narrow band ultraviolet (NB-UVB) in adult patients with PN. This is a retrospective chart review of adult patients diagnosed with PN at Hamilton Health Science Center and/or McMaster University in Hamilton, Ontario, between 2015 and 2023. The study included 81 patients (57% female). The mean age was 52.8 years, and the mean age of PN diagnosis was 50 years. Reported symptoms included: itching (100%), dry skin (53%), pain (17%), and burning sensation (5%). Lower and upper extremities were the most common areas involved in 93% and 69%, respectively. Mental health disorders were present in 79% of patients, with depression (58%) and anxiety (52%) being the most common. Atopic dermatitis was the most common skin comorbidity noted. Treatments used included cyclosporine, and NB-UVB, and MTX, which resulted in significant improvement of pruritus in 38%, 35%, and 31% of patients, respectively, at week 16. PN is associated with increased risk of mental health disorders and other medical comorbidities. Cyclosporine, methotrexate, and NB-UVB therapy may be effective treatment options, however clinicians must consider the potential short- and long-term adverse effects of these treatments.

Severity, impact on quality of life and mental health burden of pruritus in prurigo nodularis: a cross-sectional study of a diverse patient cohort.

We performed a cross-sectional study using validated survey instruments, finding severe pruritus, reduced quality of life (QoL) and a significant mental health burden in a diverse cohort of patients with prurigo nodularis (PN) from the USA. Itch severity and QoL scores were comparable to those found in European populations, aside from ItchyQoL scores (higher scores in this US cohort). Black patients reported higher itch intensity scores than White patients. More than 37% of patients met the cutoff for severe depression, but only 26% had a clinical diagnosis of depression. Dermatologists should be aware that PN extends beyond severe pruritus, consider screening for psychiatric comorbidities and address other concerns that affect QoL as needed.

Dysregulation of the Skin-Liver Axis in Prurigo Nodularis: An Integrated Genomic, Transcriptomic, and Population-Based Analysis.

Pruritus has long been linked to hepatic dysfunction; however, there are limited data characterizing the association between liver disease and prurigo nodularis (PN), a chronic inflammatory skin disease featuring severe pruritis. We thus conducted a cross-sectional analysis of hepatic comorbidities in PN patients using TriNetX, a large global health research network. This analysis revealed that PN patients had a higher risk (p < 0.001) of developing liver cirrhosis, acute and subacute hepatic failure, inflammatory liver disease, chronic hepatitis, nonalcoholic steatohepatitis, portal hypertension, fatty liver, chronic passive congestion of the liver, and hepatocellular carcinoma compared with healthy controls. The cumulative incidence of liver disease was about three times higher in PN patients compared with healthy controls. These findings provided the basis for translational studies to investigate a genetic mechanism for this association. Cutaneous transcriptomic analysis performed on PN patients revealed the dysregulation of genes related to hepatic failure in lesional PN compared with both nonlesional PN and control skin. Similarly, gene set variation analysis (GSVA) revealed a significantly increased (p < 0.05) activation of liver metabolism, chronic hepatic failure, acute hepatic failure, cholestatic liver disease, polycystic liver disease, and hepatocellular carcinoma pathways in lesional PN compared with control skin. A subsequent genome-wide association study (GWAS) identified shared single-nucleotide polymorphisms (SNPs) in the genes AR, EDIL3, MACROD2, PCSK5, RUNX1T1, TENM4, and ZEB2 between PN and liver disease from the FinnGen cohort. Significant dysregulation of the skin-liver axis in PN patients may explain the increased incidence and severity of hepatic comorbidities and help identify future therapeutic targets for PN.

Single-Cell RNA Sequencing Reveals Dysregulated POSTN+WNT5A+ Fibroblast Subclusters in Prurigo Nodularis

Prurigo nodularis (PN) is an intensely pruritic, inflammatory skin disease with a poorly understood pathogenesis. We performed single-cell transcriptomic profiling of 28,695 lesional and nonlesional PN cells. Lesional PN has increased dysregulated fibroblasts (FBs) and myofibroblasts. FBs in lesional PN were shifted toward a cancer-associated FB-like phenotype, with POSTN+WNT5A+ cancer-associated FBs increased in PN and similarly so in squamous cell carcinoma. A multicenter cohort study revealed an increased risk of squamous cell carcinoma and cancer-associated FB-associated malignancies (breast and colorectal) in patients with PN. Systemic fibroproliferative diseases (renal sclerosis and idiopathic pulmonary fibrosis) were upregulated in patients with PN. Ligand-receptor analyses demonstrated an FB neuronal axis with FB-derived WNT5A and periostin interactions with neuronal receptors melanoma cell adhesion molecule and ITGAV. These findings identify a pathogenic and targetable POSTN+WNT5A+ FB subpopulation that may predispose cancer-associated FB-associated malignancies in patients with PN.

Development and Validation of a Patient-Reported Outcome Measure to Assess Disease Control in Chronic Prurigo

Chronic prurigo (CPG), including prurigo nodularis, is a difficult disease to treat and considerably affects patients' quality of life. Helping patients obtain control of CPG is a major treatment goal. To develop and validate the Prurigo Control Test (PCT), a tool for assessing disease control in CPG, and to identify a cutoff value for controlled disease to aid treatment decisions. This qualitative study followed the current recommendations for patient-reported outcome measure development in the generation and validation of the PCT. The final PCT was obtained after item generation, followed by reduction and selection, and was then tested for internal consistency and test-retest reliability, convergent validity, known-group validity, screening accuracy, and banding. The item-generation phase resulted in an unselected list of 69 potential PCT items. Impact analysis, interitem correlation, and review for content (face) validity resulted in final set of 5 PCT items. The validation study was performed among patients across 2 expert centers in Germany. Data were analyzed from February 2017 to November 2019. A 5-item PCT with a recall period of 2 weeks was developed. A cutoff value of 10 points or higher was determined as suitable for identifying patients with well-controlled vs poorly controlled CPG. Of the 95 patients included in the validation study, the median (range) age was 63 (19-87) years, 50 patients (53%) were women, and the median (range) disease duration was 72 (9-774) months. The validation study yielded good internal consistency reliability (Cronbach α, 0.86) and a high degree of convergent validity. The PCT demonstrated good known-group validity and could discriminate between patients who differed in prurigo control. Test-retest reliability was high, and the intraclass correlation coefficient was 0.94, indicating excellent reproducibility. This qualitative study showed that the PCT is able to assess disease control in patients with CPG. Its retrospective approach, brevity, and simple scoring likely make the PCT suitable for clinical practice and trials.

Dermatological manifestations of HIV: Implications for esthetic and clinical management

ABSTRACT HIV/acquired immunodeficiency syndrome has significant systemic implications, with dermatological manifestations often being the earliest and most visible indicators of infection. These skin conditions can severely impact patients’ quality of life and esthetic health. This review explores a broad range of dermatological changes associated with HIV, including HIV-specific dermatoses such as papular pruritic eruption, xerosis, eosinophilic folliculitis, prurigo nodularis, and papular mucinosis. It also covers common dermatoses such as seborrheic dermatitis, psoriasis, pityriasis rubra pilaris, and hidradenitis suppurativa. In addition, the review examines skin infections (fungal, bacterial, and viral), HIV-related malignancies (Kaposi’s sarcoma and cutaneous lymphomas), and antiretroviral therapy (ART)-related skin changes including exanthematous reactions and lipodystrophy. Special attention is given to the management of these conditions, which often involves a combination of topical and systemic treatments along with ART. The phenomenon of immune reconstitution inflammatory syndrome and its dermatological manifestations are also discussed, highlighting the complexities of managing skin reactions as the immune system recovers. Furthermore, the review addresses ectoparasitic infestations and skin complications arising from intravenous drug use, which are prevalent in HIV patients. Effective management of these dermatological issues is crucial not only for improving physical health but also for addressing the profound esthetic concerns that affect patients’ psychological well-being. Early recognition and appropriate treatment strategies can lead to better patient outcomes and enhanced quality of life. Advances in ART and dermatological therapies continue to improve the care provided to HIV patients, ensuring a comprehensive approach that considers both medical and esthetic aspects of their health. This review underscores the importance of a multidisciplinary approach in managing the diverse and complex skin conditions associated with HIV.

Management of the adverse effects of dupilumab in atopic dermatitis and prurigo nodularis

Management of the adverse effects of dupilumab in atopic dermatitis and prurigo nodularis

Treatment With Upadacitinib in Refractory Prurigo Nodularis: A Prospective Cohort Study.

Prurigo nodularis (PN) is a chronic neuroinflammatory dermatosis with severe pruritus that has limited efficacy in various conventional treatments. This study investigated the outcomes of upadacitinib treatment in patients with refractory PN. A prospective study was conducted to screen for potential chronic infections prior to treatment. Upadacitinib was administered at a daily dose of 15 mg for 24 weeks, and the treatment response was assessed using the itch Numeric Rating Scale (NRS), investigator's Global Assessment (IGA), and Dermatology Life Quality Index (DLQI). Adverse events were monitored at each visit. Ten patients, with an average age of 48.8 years, were included in the study. All participants were treated with systemic cyclosporine before receiving upadacitinib, which yielded limited responses. At baseline, the mean prurigo severity scores assessed using the IGA, DLQI, and itch NRS were 3.4, 17.8, and 8.1, respectively; after 24 weeks of treatment, these scores significantly reduced to 1.0, 0.6, and 0.8, respectively. No severe adverse effects were observed. In conclusion, upadacitinib could be considered an alternative therapeutic option with good tolerability for refractory PN.