Prurigo Nodularis Research Articles

Risk of incident sleep disorders in patients with prurigo nodularis: A population-level analysis using The Health Improvement Network

Prurigo nodularis (PN) is a chronic inflammatory skin condition characterized by severely itchy and often painful bumps on the arms, legs, and trunk. It is unknown whether patients with PN have increased risk of developing sleep disorders. To evaluate the association of PN with sleep disorders. This retrospective, population-level, matched-cohort study was conducted using The Health Improvement Network. The study included 4193 patients with newly diagnosed PN and 4193 age, sex, and race/ethnicity-matched controls. A Cox regression model was used to assess the development of sleep disorders, including insomnia, sleep apnea, and restless legs syndrome, in patients with PN compared with control patients. Compared with controls, PN was associated with insomnia (adjusted hazard ratio [aHR]=1.77; 95% CI=1.48-2.12) and overall sleep disorder (aHR=1.72; 95% CI=1.46-2.02), but not with sleep apnea (aHR=1.51; 95% CI=0.93-2.44) or restless legs syndrome (aHR=1.54; 95% CI=0.92-2.57). As a retrospective cohort study, our analysis is subject to potential confounders not already included. PN was associated with subsequent development of insomnia. Thus, clinicians should consider insomnia among patients with PN and develop strategies for treatment and prevention.

Single-cell profiling of prurigo nodularis demonstrates immune-stromal crosstalk driving profibrotic responses and reversal with nemolizumab

Prurigo nodularis (PN) is a chronic neuroimmune skin disease characterized by bilaterally distributed pruritic hyperkeratotic nodules on extremities and trunk. Neuroimmune dysregulation and chronic scratching are believed to both induce and maintain the characteristic lesions. This study sought to provide a comprehensive view of the molecular pathogenesis of PN at the single-cell level to identify and outline key pathologic processes and the cell types involved. Features that distinguish PN skin from the skin of patients with atopic dermatitis were of particular interest. We further aimed to determine the impact of the IL31RA antagonist, nemolizumab, and its specificity at the single-cell level. Single-cell RNA-sequencing of skin from 15 healthy donors and nonlesional and lesional skin from 6 patients each with PN and atopic dermatitis, combined with spatial-sequencing using the 10x Visium platform. Integration with bulk RNA-sequencing data from patients treated with nemolizumab. This study demonstrates that PN is an inflammatory skin disease characterized by both keratinocyte proliferation and activation of profibrotic responses. This study also demonstrates that the COL11A1+ fibroblast subset is a major contributor to fibrosis and is predominantly found in the papillary dermis of PN skin. Activation of fibrotic responses is the main distinguishing feature between PN and atopic dermatitis skin. This study further shows the broad effect of nemolizumab on PN cell types, with a prominent effect driving COL11A1+ fibroblast and keratinocyte responses toward normal. This study provides a high-resolution characterization of the cell types and cellular processes activated in PN skin, establishing PN as a chronic fibrotic inflammatory skin disease. It further demonstrates the broad effect of nemolizumab on pathological processes in PN skin.

Identification of clinical predictors for dupilumab dose spacing in adults with atopic dermatitis: a real-world study

BackgroundDupilumab is a monoclonal antibody against the IL-4/IL-13 receptor-subunit approved for the treatment of moderate-severe atopic dermatitis (AD). Some attempts to increase dose interval have been described in both trial and real-world settings.ObjectiveThis study aimed to identify predictive clinical and demographic factors affecting patient selection for dose spacing or treatment withdrawal due to satisfactory response.Materials and methodsThis retrospective study included adult patients with moderate-to-severe AD treated with dupilumab for at least 16 weeks. Descriptive statistics were performed to analyze demographic and clinical variables. Logistic regression models were used to identify predictor variables.ResultsA total of 818 adult patients with moderate-to-severe AD was included in the study and 12% (97/818) of them performed dose spacing to 3–4 weeks or treatment withdrawal (8%, 67/818). The presence of non-cutaneous atopic manifestations (OR = 1.59, 95%CI = 1.06–2.38, p = 0.024), prurigo nodularis phenotype (OR = 4.5, 95%CI = 1.87–10.9, p = 0.001) and the age at treatment initiation (OR = 1.82, 95%CI = 1.12–2.94, p = 0.015) were confirmed as the strongest predictors of dose spacing or treatment withdrawal while maintaining dupilumab effectiveness.ConclusionOur findings contribute to define the patient profile that could maintain the therapeutic response after dose spacing or treatment withdrawal.

Prevalence and comorbidity burden of prurigo nodularis in United States adults enrolled in the All of Us research program

Prevalence and comorbidity burden of prurigo nodularis in United States adults enrolled in the All of Us research program

Prurigo Nodularis onset during secukinumab treatment of psoriasis: a case report

BackgroundSecukinumab has been approved by the U.S. FDA and the European Medicines Agency for the treatment of moderate-to-severe plaque psoriasis and psoriatic arthritis with the documented adverse effects. Here we reported in one case that a new symptom, Prurigo Nodularis (PN), developed during the programmed dosing of secukinumab.Case introductionA 22-years-old male with a 6-month history of severe plaque psoriasis vulgaris was presented to the dermatology clinic two weeks after the fifth serial weekly doses of secukinumab, for the reason of the outbreaks of multiple erythematous papules and pruritus nodules on the trunk and extremities. Physical examination showed that psoriatic rash were under effective control with the previous targeted therapy of secukinumab for plaque psoriasis vulgaris, but new dermatologic condition was spotted with multiple edematous red firm papules on the trunk and extremities, in the form of soy or hemispherical nodules, red in color, firm to touch, with some ulcerated crusts visible at tops, but negative Auspitz sign. Pathological examination confirmed these papules as PN.ConclusionThis case report is shared to inform clinicians about an unannounced adverse effect of the secukinumab in the treatment of psoriasis, and it is recommended that patients be carefully informed of the possible risk of PN before starting treatment.

P71 Dupilumab improves patient-reported itch and other signs and symptoms of disease in adults with prurigo nodularis (LIBERTY-PN PRIME and PRIME2)

Abstract Prurigo nodularis (PN) is characterized by the presence of itchy nodules on the trunk/extremities and is often accompanied by skin pain and sleep disruption. Patient needs are highest regarding symptom control and improvement of itch, which is one of the main hallmarks of PN. Using pooled blinded data from two randomized, double-blind, placebo-controlled phase III trials of dupilumab in adults with PN uncontrolled on topical therapies, LIBERTY-PN PRIME (NCT04183335) and PRIME2 (NCT04202679), the psychometric validation and within-patient meaningful change thresholds for three patient-reported outcome (PRO) instruments of the trial were assessed in patients with PN: Worst Itch Numerical Rating Scale (WI-NRS), Skin Pain-NRS and Sleep-NRS. The proportion of patients achieving clinically meaningful improvement in these PRO scores in LIBERTY-PN PRIME and PRIME2 was investigated in this post hoc analysis. Adults with PN inadequately controlled on topical prescription therapies, or when those therapies were not advisable, were randomized 1 : 1 to dupilumab 300 mg every 2 weeks or matched placebo. Here, we report the proportion of patients meeting a defined improvement threshold in weekly averages from baseline to week 24 of ≥ 4 points in WI-NRS, ≥ 4 points in Skin Pain-NRS and ≥ 2 points in Sleep-NRS (within-patient meaningful improvement thresholds defined in the context of the LIBERTY-PN PRIME and PRIME2 studies, range 0–10), and the proportion of patients who achieved a new composite endpoint, meaningful improvement in WI-NRS and either Skin Pain-NRS or Sleep-NRS at week 24. A total of 311 patients were randomized (dupilumab, n = 153; placebo, n = 158). Baseline scores for WI-NRS, Skin Pain-NRS and Sleep-NRS were balanced between treatment groups. Significantly more patients treated with dupilumab vs. placebo achieved in-­patient meaningful improvement in WI-NRS (58.8% vs. 19.0%; P < 0.001), Skin Pain-NRS (49.7% vs. 20.9%; P < 0.001) and Sleep-NRS (42.5% vs. 23.4%; P < 0.001) from baseline to week 24. More patients treated with dupilumab experienced clinically meaningful improvement in WI-NRS and either Skin Pain-NRS or Sleep-NRS vs. placebo (53.6% vs. 18.4%; P < 0.001). Adults with PN uncontrolled on topical therapies treated with dupilumab achieved statistically significant and clinically meaningful improvement in itch, skin pain and sleep quality individually, and in itch combined with either skin pain or sleep. The safety profile of dupilumab was consistent with the known safety profile in its approved indications. Funding sources: research sponsored by Sanofi and Regeneron Pharmaceuticals Inc.

CPC05 A case of extensive hypertrophic lupus erythematosus responsive to topical steroids

Abstract Hypertrophic lupus erythematosus (HLE) is a rare variant of lupus erythematosus, occurring in 2% of cases of chronic cutaneous lupus erythematosus (CCLE). It is an exaggerated proliferative epithelial response manifesting as verrucous-appearing hypertrophic indurated lesions occurring on sun-exposed sites. We present a case of the development of extensive HLE in a patient with subacute cutaneous lupus erythematosus (SCLE) with underlying pulmonary malignancy. A 74-year-old woman with Sjögren syndrome presented to dermatology with a 2-month history of a rash affecting her face and décolletage. Laboratory studies illustrated elevated antinuclear and anti-Ro antibodies. Biopsy from her chest confirmed SCLE. Malignancy screening revealed T1aN0 pulmonary lepidic adenocarcinoma, which was successfully managed with a lower lobectomy. Hydroxychloroquine was initially trialled but required discontinuation following intolerable side-effects. Mepacrine was then initiated, which allowed clearance of the rash, alongside yellow discoloration of the skin. Six months later, she developed a raised pruritic rash on her arms, legs and buttocks, resistant to current management alongside a trial of mycophenolate mofetil. Examination revealed violaceous hypertrophic plaques affecting 40% of her body-­surface area. The differential included hypertrophic lichen planus, nodular prurigo and HLE. Repeat lesional biopsies highlighted a lichenoid inflammatory infiltrate with overlying scale, favouring HLE. Owing to patient choice, topical mometasone furoate 0.1% was used to manage cutaneous disease, with a reduction in lesion size. HLE is a distinct subset of CCLE, regarded as a separate entity to SCLE. Twenty per cent of patients with SCLE also exhibit other types of cutaneous lupus erythematosus (CLE) lesions. No cases in the literature describe progression from SCLE to CCLE, or HLE, in particular. Hallmarks of HLE include verrucous lesions, chronicity and treatment resistance. Early recognition and follow-up are essential as malignancy may arise in long-standing lesions. Lung adenocarcinomas and hypertrophic lupus are both associated with p53 mutations and decreased granzyme B expression. Mutated p53 results in constitutive cell proliferation and DNA damage can accumulate in cells. Granzyme B is a protease in cytotoxic T cells involved in immune-mediated cell lysis. Both processes result in the potential to produce exaggerated hyperproliferative lesions, such as those observed in HLE and the lepidic adenocarcinomas. HLE is a rare clinical entity that can be easily misdiagnosed clinically and histopathologically. Increased awareness of this condition is essential to highlight the variety of clinical presentations of uncommon variants of CLE, to ensure they are considered while approaching clinical diagnosis.

Comparison between dupilumab and oral Janus kinase inhibitors in the treatment of prurigo nodularis with or without atopic dermatitis in a tertiary care center in Singapore

Comparison between dupilumab and oral Janus kinase inhibitors in the treatment of prurigo nodularis with or without atopic dermatitis in a tertiary care center in Singapore

436 Nemolizumab monotherapy was associated with significant improvements in prurigo activity score in adult patients with moderate-to-severe prurigo nodularis: results from a phase 3 trial (OLYMPIA 2)

Abstract Prurigo nodularis (PN) or chronic nodular prurigo is a debilitating, and severely pruritic neuroimmune skin disease, predominantly characterized by the presence of multiple pruriginous nodules symmetrically distributed in large areas of the trunk and extremities. Other pruriginous lesions such as papules, plaques and umbilicated lesions can also be present. Prurigo nodularis dramatically reduces quality of life among patients, including disruption of physical, emotional and psychosocial domains. Therapeutic goals are primarily to reduce pruritus and improve lesion healing. Interleukin-31 (IL-31) is a neuroimmune cytokine highly expressed in PN lesional skin that bridges the immune and nervous systems, functioning as a central mediator of main pathophysiological processes in PN. Prurigo nodularis has a unique immunophenotype, with recent studies revealing activation of Type-2-inflammation, and also induction of Th17 and Th22 pathways. Nemolizumab, an IL-31 receptor alpha antagonist, was shown to downregulate these pathways and was associated with significant improvements in pruritus and lesion healing in patients with PN in a phase-2-trial. Here, the authors report additional outcomes on excoriations and healing of pruriginous lesions from the OLYMPIA 2 phase-3-study after 16 weeks of treatment with nemolizumab. This study aims to assess the safety and efficacy of nemolizumab compared with placebo in ≥18-year-old patients with moderate-to-severe PN after a 16-week treatment period. OLYMPIA 2 (NCT04501679) was a phase 3, global, multicenter, double-blind study in adults with PN presenting ≥20 nodules, Investigator’s Global Assessment (IGA) score ≥3 (range 0–4) and Peak Pruritus Numerical Rating Scale (PP-NRS) score ≥7.0 (range: 0–10). Patients were randomized (2 : 1) to receive nemolizumab (n = 183) or matching placebo (n = 91). Following an initial 60 mg loading dose, patients weighing <90 kg received 30 mg every 4 weeks (q4w) and those weighing ≥90 kg received 60 mg q4w, for a period of 16 weeks, during which, treatment with topical corticosteroids (TCS) or topical calcineurin inhibitors (TCI)was not allowed. The primary endpoints were proportion of patients with a ≥4-point improvement in weekly average PP-NRS and proportion of patients with IGA Success for nodule healing [score of 0 (clear) or 1 (almost clear) and a ≥2-grade improvement] at Week (W) 16. Key secondary endpoints included proportion of patients with ≥4-point improvement in PP-NRS at W4 and Sleep Disturbance NRS (SD-NRS) at W4 and W16. Other secondary endpoints included percentage of patients with pruriginous lesions with excoriations/crusts [Prurigo activity score (PAS) item 5a], healed pruriginous lesions (PAS item 5b) and <20 pruriginous lesions (PAS item 2) at each visit through W16. The baseline demographic and clinical characteristics were balanced between the groups. At W16, both primary endpoints, were met (P < 0.0001). A significantly higher proportion of patients in the nemolizumab-treated group vs. placebo-treated group achieved a ≥4-point improvement in weekly average PP-NRS score (56.3% vs. 20.9%) and IGA success (37.7% vs. 11.0%) at W16. The study also met all key secondary endpoints on pruritus and sleep disturbance (P < 0.0001). Among other secondary endpoints, a significantly higher proportion of patients in the nemolizumab-treated group vs. placebo-treated group achieved mild disease activity with ≤25% excoriations/crusts (PAS item 5a) (56.8% vs. 23.1%; P < 0.0001 at W16), >75% healed lesions (PAS item 5b) (55.2% vs. 16.5%; P < 0.0001 at W16) and <20 pruriginous lesions (PAS item 2) (54.6% vs. 22.0%; P < 0.0001 at W16) at each visit, from baseline through W16. Treatment-emergent adverse events (AEs) were reported in 61.2% of nemolizumab-treated patients and 52.7% of placebo-treated patients, while serious AEs were reported in 2.2% of nemolizumab-treated patients and 5.5% of placebo-treated patients. Nemolizumab monotherapy (without TCS or TCI) demonstrated a significant reduction of pruritus as well as excoriations and number of pruriginous lesions after 16 weeks of treatment in patients with moderate-to-severe PN. The safety profile was consistent with that previously observed.

The Sleep Disturbance Numerical Rating Scale: Content Validity, Psychometric Validation, and Meaningful Within-Patient Change in Prurigo Nodularis.

Sleep is often disturbed in patients with prurigo nodularis (PN). To address the lack of validated patient-reported outcome (PRO) measures for quantifying sleep disturbance in PN, we evaluated the Sleep Disturbance Numerical Rating Scale (SD NRS) as a single-item PRO measure for quantifying sleep disturbance in PN. Adults with PN participated in qualitative interviews, which included concept elicitation and cognitive debriefing of the SD NRS. The SD NRS was evaluated psychometrically using data from a phase 2 randomized trial in adults with PN (NCT03181503). Other PRO assessments included the Average Pruritus (AP) NRS, AP Verbal Rating Scale (VRS), peak pruritus (PP) NRS, PP VRS, and Dermatology Life Quality Index (DLQI). Reliability, validity, and responsiveness of the SD NRS were evaluated, and meaningful within-patient change was estimated from qualitative interview responses and quantitative trial data. All interview participants (N = 21) experienced sleep disturbance and most (95%) understood the SD NRS as intended. The SD NRS demonstrated test-retest reliability based on intra-class correlation coefficients for itch-stable participants of 0.87 for the AP VRS and 0.76 for the PP VRS. At baseline, Spearman's rank-order correlation coefficients were moderate to strong (0.3-0.8) between the SD NRS and the AP NRS, AP VRS, PP NRS, PP VRS, and DLQI. Known-groups validity was demonstrated by higher (worse) SD NRS scores in participants with worse scores on the AP NRS, AP VRS, PP VRS, and DLQI. Improvements in SD NRS scores were greater in participants classified as "improved" versus "worsened/unchanged" on the anchor PROs. A 2- to 4-point decrease on the 11-point SD NRS scale was identified as a meaningful within-patient change. The SD NRS is a well-defined, reliable, and valid PRO measure that can be used in daily practice and clinical trials to capture sleep disturbance in adults with PN.

A Polygenic Risk Score for Predicting Racial and Genetic Susceptibility to Prurigo Nodularis

Prurigo nodularis (PN) is an understudied inflammatory skin disease characterized by pruritic, hyperkeratotic nodules. Identifying the genetic factors underlying PN could help to better understand its etiology and guide the development of therapies. In this study, we developed a polygenic risk score that predicts a diagnosis of PN (OR= 1.41, P= 1.6× 10-5) in two independent and continentally distinct populations. We also performed GWASs, which uncovered genetic variants associated with PN, including one near PLCB4 (rs6039266: OR= 3.15, P= 4.8× 10-8) and others near TXNRD1 (rs34217906: OR= 1.71, P= 6.4× 10-7; rs7134193: OR= 1.57, P= 1.1× 10-6). Finally, we discovered that Black patients have over a two-times greater genetic risk of developing PN (OR= 2.63, P= 7.8× 10-4). Combining the polygenic risk score and self-reported race together was significantly predictive of PN (OR= 1.32, P= 4.7× 10-3). Strikingly, this association was more significant with race than after adjusting for genetic ancestry. Because race is a sociocultural construct and not a genetically bound category, our findings suggest that genetics, environmental influence, and social determinants of health likely affect the development of PN and may contribute to clinically observed racial disparities.

Recalcitrant prurigo nodularis after COVID‐19 vaccination and successfully treated by dupilumab

AbstractPrurigo nodularis (PN) is a chronic, inflammatory skin condition characterized by the presence of pruritic nodules. We report a 57‐year‐old woman in whom PN might have been induced by COVID‐19 vaccination. PN lesions started 2 days after she received the second dose of COVID‐19 vaccine. She had a poor response to a variety of treatments but achieved satisfactory efficacy after Dupilumab therapy, an interleukin‐4 receptor inhibitor.

Single-cell RNA sequencing defines disease-specific differences between chronic nodular prurigo and atopic dermatitis

Chronic nodular prurigo (CNPG) is an inflammatory skin disease that is maintained by a chronic itch-scratch cycle likely rooted in neuroimmunological dysregulation. This condition may be associated with atopy in some patients, and there are now promising therapeutic results from blocking type 2 cytokines such as IL-4, IL-13, and IL-31. This study aimed to improve the understanding of pathomechanisms underlying CNPG as well as molecular relationships between CNPG and atopic dermatitis (AD). We profiled skin lesions from patients with CNPG in comparison with AD and healthy control individuals using single-cell RNA sequencing combined with T-cell receptor sequencing. We found type 2 immune skewing in both CNPG and AD, as evidenced by CD4+ helper T cells expressing IL13. However, only AD harbored an additional, oligoclonally expanded CD8A+IL9R+IL13+ cytotoxic T-cell population, and immune activation pathways were highly upregulated in AD, but less so in CNPG. Conversely, CNPG showed signatures of extracellular matrix organization, collagen synthesis, and fibrosis, including a unique population of CXCL14-IL24+ secretory papillary fibroblasts. Besides known itch mediators such as IL31 and oncostatin M, we also detected increased levels of neuromedin Bin fibroblasts of CNPG lesions compared with AD and HC, with neuromedin B receptors detectable on some nerve endings. These data show that CNPG does not harbor the strong disease-specific immune activation pathways that are typically found in AD but is rather characterized by upregulated stromal remodeling mechanisms that might have a direct impact on itch fibers.

Tralokinumab shows clinical improvement in patients with prurigo nodularis-like phenotype atopic dermatitis: A multicenter, prospective, open-label case series study

There are several phenotypes of atopic dermatitis (AD). 1 Girolomoni G. de Bruin-Weller M. Aoki V. et al. Nomenclature and clinical phenotypes of atopic dermatitis. Ther Adv Chronic Dis. 2021; 2620406223211002979 Google Scholar The prurigo nodularis (PN)-like phenotype occurs in nearly one-half of the patients with AD. 1 Girolomoni G. de Bruin-Weller M. Aoki V. et al. Nomenclature and clinical phenotypes of atopic dermatitis. Ther Adv Chronic Dis. 2021; 2620406223211002979 Google Scholar In all AD phenotypes, chronic itch usually leads to an itch-scratch cycle with the development of secondary lesions. These include, in the PN-like phenotype, excoriated hyperkeratotic, intensely itchy papules and nodules in areas accessible to scratch. 1 Girolomoni G. de Bruin-Weller M. Aoki V. et al. Nomenclature and clinical phenotypes of atopic dermatitis. Ther Adv Chronic Dis. 2021; 2620406223211002979 Google Scholar An emergent role of the type 2 cytokines, including interleukin (IL) 4, IL-13, IL-31, and IL-5, has been suggested in the pathogenesis underlying AD itch. IL-13 is a potent enhancer of the neuronal response to different itch stimuli. 2 Miron Y. Miller P.E. Hughes C. et al. Mechanistic insights into the antipruritic effects of lebrikizumab, an anti–IL-13 mAb. J Allergy Clin Immunol. 2022; 150: 690-700 Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar Tralokinumab, a fully human IgG4 monoclonal antibody neutralizing IL-13, is a novel treatment that has demonstrated safety and efficacy in clinical trials in treating adult patients with moderate-to-severe AD. 3 Wollenberg A. Blauvelt A. Guttman-Yassky E. et al. Tralokinumab for moderate-to-severe atopic dermatitis: results from two 52-week, randomized, double-blind, multicentre, placebo-controlled phase III trials (ECZTRA 1 and ECZTRA 2). Br J Dermatol. 2021; 184: 437-449 Crossref PubMed Scopus (170) Google Scholar In our open-label, retrospective case series study, tralokinumab improved clinical manifestations in 2 patients presenting with PN-like phenotype. 4 Pezzolo E. Naldi L. Tralokinumab in the treatment of resistant atopic dermatitis: an open-label, retrospective case series study. J Eur Acad Dermatol Venereol. 2023; 37: e644-e645 Crossref Scopus (2) Google Scholar Therefore, we prospectively investigated tralokinumab efficacy and safety in treating for at least 16 weeks, 17 adult patients with moderate-to-severe PN-like phenotype AD at 5 dermatology tertiary referral centers, from July 2021 to November 2022. Patients were eligible for treatment with tralokinumab after failing the first-line approved biologic treatment dupilumab, without achieving eczema area and severity index (EASI)-50 after 16 weeks of treatment. Written informed consent was obtained for each patient. At baseline, patients (mean age, 60.75 years; 76.5% women) presented moderate-to-severe PN-like phenotype AD and with means (ranges) EASI of 27.2 (16-45), Investigator Global Assessment (IGA) of 3.7 (3-4), numeric rating scale (NRS)-itch of 9.8 (8-10), NRS-sleeplessness of 8.9 (6-10), and dermatology life and quality index (DLQI) of 16.3 (14-24). Seventy percent of patients used concomitant topical corticosteroids at baseline. Patients reached EASI-50 within 4 weeks, EASI-75 within 12 weeks, and EASI-90 within 32 weeks (mean EASI reduction from 27.2-1.7, P <.001) (Fig 1). The mean NRS-itch and sleeplessness and DLQI values significantly decreased as early as week 4 (P <.001) and progressively reduced after 16-week continuous treatment. Tralokinumab resulted in complete or almost complete clinical remission (IGA 0 or 1) in 76% (13/17) of patients, in 47% (8/17) within week 12, in 23% within week 32, and 6% within week 64, and an at least 2-grade IGA reduction in the others (24%) (Fig 2). Both patients with 16-weeks treatment observation (8/17) and patients with 32 or 64 weeks of continuous treatment (9/17) maintained clinical efficacy without reporting any serious adverse effect. 5 Licata G, Tancredi V, Pezzolo E, et al. Efficacy and safeness of tralokinumab in patients with atopic dermatitis who developed conjunctivitis under dupilumab: a case series. J Eur Acad Dermatol Venereol. Published online April 5, 2023. https://doi.org/10.1111/jdv.19108 Google Scholar Mild conjunctivitis represented the main adverse effect (12%), followed by injection-site reaction, localized urticaria, and mild herpetic stomatitis. Fig 2Atopic dermatitis severity assessed by the Investigator Global Assessment score at different times. IGA, Investigator Global Assessment. View Large Image Figure Viewer Download Hi-res image

Dupilumab in patients with prurigo nodularis: two randomized, double-blind, placebo-controlled phase 3 trials

Prurigo nodularis (PN) is a chronic inflammatory skin disease with intensely pruritic nodules. The LIBERTY-PN PRIME and PRIME2 phase 3 trials enrolled adults with PN with ≥20 nodules and severe itch uncontrolled with topical therapies. Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin (IL)-4 and IL-13. Patients were randomized 1:1 to 300 mg dupilumab or placebo subcutaneously every 2 weeks for 24 weeks. The primary endpoint was pruritus improvement, measured by proportion of patients with a ≥4-point reduction in Worst Itch Numeric Rating Scale (WI-NRS) from baseline at week 24 (PRIME) or week 12 (PRIME2). Key secondary endpoints included nodule number reduction to ≤5 at week 24. PRIME and PRIME2 enrolled 151 and 160 patients, respectively. Both trials met all the pre-specified primary and key secondary endpoints. A ≥4-point WI-NRS reduction at week 24 in the dupilumab and placebo arms was achieved by 60.0% and 18.4% of patients, respectively, in PRIME (95% confidence interval (CI), 27.8–57.7 for the difference, P < 0.001) and at week 12 by 37.2% and 22.0% of patients, respectively, in PRIME2 (95% CI, 2.3–31.2; P = 0.022). Dupilumab demonstrated clinically meaningful and statistically significant improvements in itch and skin lesions versus placebo in PN. Safety was consistent with the known dupilumab safety profile.ClinicalTrials.gov identifiers: NCT04183335 and NCT04202679.

Skin Microbiome in Prurigo Nodularis.

Prurigo nodularis (PN) is a chronic condition characterized by the presence of nodular lesions accompanied by intense pruritus. The disease has been linked to several infectious factors, but data on the direct presence of microorganisms in the lesions of PN are scarce. The aim of this study was to evaluate the diversity and composition of the bacterial microbiome in PN lesions by targeting the region V3-V4 of 16S rRNA. Skin swabs were obtained from active nodules in 24 patients with PN, inflammatory patches of 14 patients with atopic dermatitis (AD) and corresponding skin areas of 9 healthy volunteers (HV). After DNA extraction, the V3-V4 region of the bacterial 16S rRNA gene was amplified. Sequencing was performed using the Illumina platform on the MiSeq instrument. Operational taxonomic units (OTU) were identified. The identification of taxa was carried out using the Silva v.138 database. There was no statistically significant difference in the alpha-diversity (intra-sample diversity) between the PN, AD and HV groups. The beta-diversity (inter-sample diversity) showed statistically significant differences between the three groups on a global level and in paired analyses. Staphylococcus was significantly more abundant in samples from PN and AD patients than in controls. The difference was maintained across all taxonomic levels. The PN microbiome is highly similar to that of AD. It remains unclear whether the disturbed composition of the microbiome and the domination of Staphylococcus in PN lesions may be the trigger factor of pruritus and lead to the development of cutaneous changes or is a secondary phenomenon. Our preliminary results support the theory that the composition of the skin microbiome in PN is altered and justify further research on the role of the microbiome in this debilitating condition.

Prurigo Nodularis in Fibrocalculous Pancreatic Diabetes (FCPD)

Fibrocalculous Pancreatic Diabetes (FCPD) is a secondary form of diabetes mellitus due to chronic nonalcoholic calcific pancreatitis. Prurigo nodularis is seen in various dermatological diseases, but also seen in hematological and metabolic diseases (such as solid tumors, lymphoma, diabetes mellitus).

Prurigo nodularis is highly linked with neural sensitization disorders of pain amonghospitalized adults in the United States - National Inpatient Sample 2016-2019.

This study demonstrates a high association between prurigo nodularis (PN) and central neural sensitization diseases of pain, such as fibromyalgia, chronic interstitial cystitis and irritable bowel syndrome – possibly indicating that further research is needed to compare the role of neural sensitization in central diseases of pain to the role of neural sensitization in PN.

1567 Single-cell RNA sequencing reveals unique fibroblast subclusters in prurigo nodularis

1567 Single-cell RNA sequencing reveals unique fibroblast subclusters in prurigo nodularis

018 Evidence for IL-31/IL-31RA axis involvement in psoriasis and autoimmune skin diseases beyond atopic dermatitis and prurigo nodularis

018 Evidence for IL-31/IL-31RA axis involvement in psoriasis and autoimmune skin diseases beyond atopic dermatitis and prurigo nodularis