Poster
Title: Nemolizumab long-term safety and efficacy up to 104 weeks in the ARCADIA open-label extension study in adolescents and adults with moderate-to-severe atopic dermatitis
Jonathan I. Silverberg George Washington University School of Medicine and Health Sciences, Washington, DC, USA
Diamant Thaçi/University of Lübeck, Lübeck, Germany; Marie Tauber/Lyon Sud Hospital, Hospices Civils de Lyon, Inserm U1111 Centre International de Recherche en Infectiology, Lyon, France; Linda Stein-Gold/ Dermatology Research, Detroit, MI, USA; Marjolein S. De Bruin-Weller/ Utrecht University and UMC Utrecht, Utrecht, Netherlands; Kim A. Papp/Alliance Clinical Trials and Probity Medical Research, Waterloo, ON, Canada and University of Toronto, Toronto, ON, Canada; Matthias Augustin/University Medical Center Hamburg, Hamburg, Germany; Adam Reich/University of Rzeszów, Rzeszów, Poland; Matthew J. Zirwas/Ohio State University, Columbus, OH, USA; Soo Yeon Cheong/Galderma Laboratories, Dallas, TX, USA; Liliana Ulianov/Galderma R&D, Zug, Switzerland; Christophe Piketty/Galderma R&D, Zug, Switzerland
Objectives: The ARCADIA long-term extension study (NCT03989206; 200-week duration) aimed to evaluate safety and efficacy of nemolizumab in moderate-to-severe AD. Methods: This prospective, open-label study enrolled patients who were either nemolizumab-previously experienced [NPE] or nemolizumab-naïve [NN] from ARCADIA 1&2 phase 3 and other nemolizumab studies. Patients received nemolizumab 30mg Q4W+TCS with/without TCI. Efficacy results presented here include proportion of patients with IGA-0/1, EASI-75 and EASI-90, changes in SCORAD-VAS Pruritus and Sleep and in DLQI for W56-visit (MI-MAR analysis) and for W104-visit (OC analysis). Results: At data cut-off, 56% of patients reached W104 and all patients at W56 either completed the visit/discontinued the study. Study discontinuation (due to AEs) rate was 5% in both treatment groups. At W56, proportion of NPE and NN patients achieving efficacy outcomes was 50% and 48% for IGA-0/1, 65% and 64% for EASI-75, 46% and 44% for EASI-90, 66% and 61% for ≥4-point improvement from lead-in baseline in SCORAD-VAS Pruritus and 50% and 45% for SCORAD-VAS Pruritus<2, respectively. At W104, proportion of NPE and NN patients achieving efficacy outcomes was 63% and 58% for IGA-0/1, 88% and 85% for EASI-75, 68% and 64% for EASI-90, 87% and 82% for ≥4-point improvement from lead-in baseline in SCORAD-VAS Pruritus and 70% and 67% for SCORAD-VAS Pruritus<2, respectively. Improvements in sleep mirrored those in itch. DLQI improved over time. COVID-19, nasopharyngitis and dermatitis atopic were most common AEs. Exposure-adjusted incidence rates for any TEAEs were 112.8 cases/100-person year and 117.1 cases/100-person year in NPE and NN patients, respectively. Safety results corroborated those previously reported. Conclusion: Nemolizumab was well-tolerated until W104. Continuous improvements with long-term treatment were observed in skin lesions, itch, sleep, and quality of life.
Title: Results of the APHYPAP clinical study (Aprepitant versus HYdroxyzine in combination with cytoreductive therapy for patients with myeloproliferative neoplasms suffering from Persistent Aquagenic Pruritus)
Christelle Le Gall-Ianotto Unversity of Brest, LIEN and Hospital of Brest, FRANCE
Verdet R 3, Consigny M 3, Gasse A 4, Fiedler A 5,6, Carlhant- Kowalski D 7, Misery L 1,2 and Ianotto JC 8,9 3 Research and Innovation Department, Brest Hospital, France, 4 Clinical investigation Center, CIC, Inserm 1412, Brest Hospital, France, 5 Department of Pharmacy, Brest Hospital, France , 6 PPRIGO (Pharmaceutical Production for Institutional Research in Western France), Brest, France, 7 Pharmacovigilance Unit, Department of Research and Innovation, Brest Hospital, France, 8 Department of
Introduction Aquagenic pruritus (AP) is a distressing symptom of myeloproliferative neoplasms (MPNs), especially polycythaemia vera (PV), and less commonly essential thrombocythaemia (ET) and primary myelofibrosis (MF). Its pathophysiology remains unclear, and effective treatments are limited. Aprepitant (a substance P receptor antagonist) and hydroxyzine have shown some efficacy in chronic pruritus, though not specifically in MPNs. Objective : Evaluate the efficacy of these drugs in treating persistent AP in MPN patients. Patients and Experimental Design This multicentre, randomised, double-blind, double-placebo trial included MPN patients (PV, ET, or MF) with persistent AP (VAS ≥6/10) despite cytoreductive therapy (≥six months). Participants received either aprepitant (80 mg/day) with a hydroxyzine placebo or hydroxyzine (25 mg/day) with an aprepitant placebo for 14 days. The primary endpoint was pruritus reduction to VAS ≤3 on day 15, with follow-up assessments on days 30, 45, and 60. Results Of the 63 patients (37 PV, 19 TE and 7 MF), 32 received aprepitant and 31 hydroxyzine. On day 15, 45.8% (aprepitant) and 47.6% (hydroxyzine) achieved the primary endpoint (VAS ≤3), with no significant difference. Mean VAS scores dropped similarly in both groups (4.5 ± 2.3 vs. 4.5 ± 2.2), indicating a decrease of at least two points from baseline, maintaining improvement through day 60 (3.9 ± 3.0 vs. 3.7 ± 2.2). During the 60-day evaluation period, patients treated with aprepitant spent 50% (5.7–81.6) of the time with an EVA score of ≤3, compared to 31.1% (0.0–68.0) for the hydroxyzine group. No haematological differences were noted between groups. Conclusion This study found no superiority of aprepitant over hydroxyzine in treating AP in MPNs. Both drugs provided lasting relief. Although aprepitant’s lack of advantage does not rule out SP's role, it suggests other mechanisms are involved.
Title: Pooled REMIX-1/-2 Phase 3 Data: Early and Sustained Symptom Improvement With Remibrutinib in Chronic Spontaneous Urticaria
Martin Metz Institute of Allergology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany and Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Immunology and Allergology, Berlin, Germany
Sarbjit Saini,1 Giselle Mosnaim,2 Ana Giménez-Arnau,3 Linfeng Li,4 El-Djouher Martzloff,5 Alis Burciu,5 Karine Lheritier,5 Martin Metz6,7 1 Johns Hopkins Asthma and Allergy Center, Baltimore, MD, USA 2 Division of Allergy and Immunology, Department of Medicine, Endeavor Health, Evanston, IL, USA 3 Department of Dermatology, Hospital del Mar and Research Institute, Universitat Pompeu Fabra, Barcelona, Spain 4 Department of Dermatology, Beijing Friendship Hospital, Capital Medical University, Beijing, China 5 Novartis Pharma AG, Basel, Switzerland 6 Institute of Allergology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany 7 Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Immunology and Allergology, Berlin, Germany
Introduction: Remibrutinib demonstrated superior efficacy versus placebo in patients with chronic spontaneous urticaria (CSU) in the REMIX-1/-2 studies. Objectives: We present pooled results from the REMIX-1/-2 studies, evaluating the efficacy and safety of remibrutinib in patients with CSU. Methods: REMIX-1/-2 were two multicentre, randomised, double-blind Phase3 studies assessing remibrutinib in patients with CSU inadequately controlled by second-generation H1-antihistamines. Patients were randomised 2:1 to receive remibrutinib 25mg twice daily (bid) or placebo. From Week24, all patients received open-label remibrutinib 25mg bid until Week52. Mean (±standard deviation [SD]) change from baseline (CFB) in weekly Urticaria Activity Score (UAS7), weekly Itch Severity Score (ISS7) and weekly Hives Severity Score (HSS7) for Weeks1, 2, 12, 24 and 52, and treatment-emergent adverse events (TEAEs) are presented. Results: Remibrutinib (n=606) showed greater mean±SD improvements versus placebo (n=306) in the following: CFB-UAS7 at Weeks1 (−11.8±9.9 vs. −3.6±7.6), 2 (−15.9±12.3 vs. −5.7±9.2), 12 (−21.3± 11.9 vs. −13.1±12.1) and 24 (−22.4±11.9 vs. −15.4±13.3); CFB-ISS7 at Weeks1 (−5.3±4.7 vs. −1.8±3.6), 2 (−7.2±5.9 vs. −2.9±4.6), 12 (−9.9±5.8 vs. −6.4±5.9) and 24 (−10.5±5.8 vs. −7.4±6.4); CFB-HSS7 at Weeks1 (−6.4±5.7 vs. −1.8±4.3), 2 (−8.7±6.9 vs. −2.8±5.0), 12 (−11.3±6.8 vs. −6.7±6.9) and 24 (−11.9±6.8 vs. −8.0±7.5). Improvements were sustained during the open-label period; patients receiving remibrutinib from initiation, and patients who transitioned to remibrutinib from placebo at Week24, showed similar improvements at Week52 (UAS7: −23.1±12.1 and −22.7±11.9; ISS7 −10.9±5.9 and −10.7±6.0; HSS7: −12.2±6.9 and −12.0±6.7, respectively). Proportion of patients with ≥1 TEAE up to Week24 was similar between remibrutinib (64.9%) and placebo (64.7%) arms, and the overall incidence did not increase up to Week52. Conclusion: In REMIX-1/-2, improvements in symptoms with remibrutinib were observed as early as Week1 and sustained until Week52, with a favourable safety profile, suggesting remibrutinib’s potential as a novel oral treatment option for fast and sustained symptom relief.
Title: Ponesimod Improves Symptoms of Itch, Soreness, Pain, and Stinging in Moderate-to-Severe Chronic Plaque Psoriasis
Vasilios Polymeropoulos Vanda Pharmaceuticals, Inc. 2200 Pennsylvania Ave NW Suite 300E, Washington, DC 20037, USA
Ponesimod, a sphingosine 1-phosphate receptor modulator, was shown to be effective at significantly improving symptoms of moderate-to-severe chronic plaque psoriasis at the Week 16 primary endpoint (p < 0.0001), as measured by the number of participants achieving at least a 75% reduction from baseline in the Psoriasis Area and Severity Index score (PASI75). This analysis evaluated the effect of ponesimod 20 mg, the EMA approved dose for the treatment of relapsing forms of multiple sclerosis, on improvement in psoriasis symptoms as reported by the participant. We evaluated psoriasis symptoms via change from baseline in question one of the Dermatology Life Quality Index (DLQI) in this phase II, double-blind, randomized, placebo-controlled, parallel group, dose-finding study. 326 participants were randomized 2:2:1 to ponesimod 20 mg, ponesimod 40 mg, or placebo, respectively. The DLQI was completed by participants at baseline, Week 8, and Week 16. The first question of the DLQI assesses how itchy, sore, painful, or stinging the participants skin has been over the last week, with options of 0 = “Not at all,” 1 = “A little,” 2 = “A lot,” and 3 = “Very Much.” Ponesimod 20 mg, as compared to placebo, demonstrated a significant reduction in reported symptoms of itchy, sore, painful, or stinging skin as early as at Week 8 of treatment in an analysis of participants with a baseline score of >1. This significant effect was also maintained at Week 16. These results suggest that ponesimod, an oral, once daily treatment, can achieve clinically meaningful improvement in psoriasis symptoms, including itch. In conjunction with ponesimod’s significant therapeutic effect, as measured by the PASI, and rapid elimination, these three features offer a versatile therapeutic option that can significantly improve patient’s quality of life.
Title: Lebrikizumab provides skin clearance and itch relief at week 16 and week 52: pooled results from 2 phase 3 studies ADvocate1 and ADvocate2
Sonja Ständer Department of Dermatology and Center for Chronic Pruritus, University Hospital Münster, Münster, Germany
Diamant Thaçi 1, Sonja Ständer 2 (Presenting author), Frank J Legat 3, H Chih-Ho Hong 4, Lidia Rodríguez Calleja 5, Francisco Hernández 5, Júlia Valls-Bancells 5, Khai Jing 6, Martin Metz 7,8 1 Institute and Comprehensive Center for Inflammatory Medicine at the University of Lübeck, Lübeck, Germany; 2 Department of Dermatology and Center for Chronic Pruritus, University Hospital Münster, Münster, Germany; 3 Department of Dermatology and Venereology, Medical University of Graz, Graz, Austria; 4 Department of Dermatology and Skin Science, University of British Columbia, Vancouver, Canada; 5 Almirall S.A., Barcelona, Spain; 6 Eli Lilly and Company, Indianapolis, USA; 7 Institute of Allergology, Charité-Universitätsmedizin Berlin, Berlin, Germany; 8 Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Immunology and Allergology, Berlin, Germany
Introduction: Lebrikizumab (LEB) is a monoclonal antibody targeting interleukin-13 for moderate-to-severe atopic dermatitis (AD). Objectives: To analyze the composite skin clearance and itch relief with LEB at week (W) 16 and W52 from pooled ADvocate1&2 trials. Methods: ADvocate1&2 were two identically designed, randomized, placebo-controlled, LEB monotherapy phase 3 trials in adult and adolescents (12-<18 years) with moderate-to-severe AD. Patients were randomized 2:1 to LEB 250 mg every 2 weeks (Q2W; 500 mg at baseline and W2) or placebo Q2W until W16. Responders were defined as patients achieving EASI75 or IGA 0/1 with ≥2-point improvement from baseline (without rescue medication) at W16. W16 LEB responders were re-randomized 2:2:1 (LEB 250 mg every 4 weeks [Q4W], LEB 250 mg Q2W or placebo) for 36 additional weeks (rescue medication permitted). This analysis reports the proportion of patients achieving EASI75 AND pruritus NRS ≥4-point improvement, EASI90 AND pruritus NRS ≥4-point improvement, and EASI ≤7 AND pruritus NRS ≥4-point improvement at W16 and W52 (on W16 LEB responders) (NRI/MI). Results: At W16, 31.9% of LEB Q2W treated patients vs 5.2% of PBO patients achieved EASI75 AND pruritus NRS ≥4-point improvement, 22.1% vs 2.8% EASI90 AND pruritus NRS ≥4-point improvement and 32.1% vs 5.8% EASI ≤7 AND pruritus NRS ≥4-point improvement (p<0.0001, all cases); with significant results already reported at W4. At W52 (LEB Q4W/LEB Q2W/placebo), 52.1%/54.3%/45.2% of patients achieved EASI75 AND pruritus NRS ≥4-point improvement, 41.7%/45.0%/31.3% of patients achieved EASI90 AND pruritus NRS ≥4-point improvement, and 53.2%/52.0%/46.0% achieved EASI ≤7 AND pruritus NRS ≥4-point improvement. Conclusion: LEB Q2W provides significant higher rates of composite skin clearance and itch relief at W16 vs PBO as early as W4. From the W16 LEB responders, high rates of composite skin clearance and itch relief are observed at W52 in both maintenance dosing regimens (LEB Q4W and Q2W).
Title: IL-4RA and SPARC silencing RNA microneedle patch for treatment of pruritic keloids
Hong Liang Tey National Skin Centre, 1 Mandalay Road, Singapore
Yong Yao Chun(1), Yingrou Tan(2,3), Caren Lum(2), Eleanor Shu Xian Chai(2,4), Eugene Ang(2), Shu Zhen Chong(3) and Timothy Thatt Yang Tan(1) 1 School of Chemistry, Chemical Engineering and Biotechnology, 62 Nanyang Drive, Singapore 637459, Singapore. 2 National Skin Centre, National Healthcare Group, 1 Mandalay Road, Singapore 308205, Singapore 3 Singapore Immunology Network, 8a Biomedical Grove, Singapore 138648, Singapore. 4 Duke-NUS Medical School, Singapore 169857
Up to 80% of keloid patients report itch, and itch is often reported to be more distressing than the appearance of keloids themselves. Targeting the important proteins involved in TH2 inflammation and collagen production addresses the fundamental processes of pruritic keloids. We synthesized 2 silencing RNAs (siRNAs) to inhibit the expression of interleukin-4 Receptor α (IL-4Rα) and secreted protein acidic and cysteine rich (SPARC), respectively. To protect them from being degraded by RNAses and to preferentially enhance their incorporation into fibroblasts, we encapsulate them in a gelatin-based nano-polymer, forming nanoplexes. We studied the effect of the dual siRNAs in reducing collagen gene expression in interleukin-4 stimulated human dermal fibroblasts (HDFs). Overall, the cellular studies demonstrated that treatment with dual siRNAs nanoplex of siIL-4Rα and siSPARC was able to inhibit collagen gene expression in HDFs in a TH2 inflammatory environment. In addition, dual siRNAs nanoplex does not result in cytotoxicity or inhibition of cellular proliferation. We further embedded the dual siRNAs into dissolving microneedles and 2 individuals with highly pruritic keloids volunteered to apply the patches daily overnight for 3 weeks. Both had substantial flattening of their keloid with resolution of itch and pain. In summary, results suggest that targeting both IL-4Rα and SPARC using the siRNA nanoplex is a promising approach for treating pruritic keloids.
Title: Altered cutaneous neuroanatomy is associated with pruritus intensity in atopic dermatitis.
Konstantin Agelopoulos University Hospital Münster, Section for Pruritus Medicine, Department of Dermatology and Center for Chronic Pruritus, Münster, Germany.
F.Witte, H.Wiegmann, C.Zeidler, A.Brenske, E.Teitge, S.Ständer
Introduction: Atopic dermatitis (AD) is a pruritic inflammatory dermatosis with alterations in peripheral neuroanatomy. However, the exact underlying mechanisms are not yet fully understood. Objectives: Decipher alterations of peripheral nerve fibers and their impact in severe atopic dermatitis Methods: Biopsies from AD patients (n=39) from pruritic lesional (PL) and non-pruritic non-lesional (NPNL) skin were used for assessment of intraepidermal nerve fiber density (IENFD) and innervation depth by PGP9.5 staining. Tight junction marker claudin-1 (CLDN-1) was assessed by immunofluorescence and IL-4RA, IL-13RA1 and IL-13RA2 by qPCR. Results: Reduced IENFD was seen in PL (5.81 fibers/mm) and NPNL (6.08). Epidermal hyperplasia in PL (vs.NPNL; p<0.001) and the depth of nerve fiber innervation into the epidermis correlated invers in PL. Unlike in NPNL, nerve fibers in PL ended more frequently in the stratum basale and lower stratum spinosum (SEC1), and less frequently reached the upper layers (SEC2=central stratum spinosum, and SEC3=upper stratum spinosum and stratum granulosum). Innervation depth correlated invers with reported itch intensity (NRS; rs=-0.463; p=0.010) and positive with CLDN-1 expression (rs=0.493; p=0.006). In PL, CLDN-1 expression was accentuated at basal layers and differed significantly from NPNL in SEC2 and SEC3, where clear expression was evident. A negative correlation between IL-4/-13 signalling and CLDN-1 was confirmed in NPNL for all analysed receptors but only for IL-13RA1 in PL. Conclusion: Epidermal hyperplasia in AD does not affect IENFD. However, there is a direct correlation between hyperplasia and the innervation depth of peripheral nerves. The innervation depth was associated with the reported pruritus intensity. Reduced innervation depth in PL could be caused by impaired epidermal tight junctions indicated by reduced CLDN-1 expression.
Title: Microbe-neuron crosstalk in itch, inflammation, and beyond
Liwen Deng Department of Immunology, Harvard Medical School, USA
Itch is a debilitating sensation that occurs primarily in the skin. The skin is the largest and most exposed barrier organ and home to a dense network of sensory neurons, immune cells, and a complex microbiome. While it has long been appreciated that pruritic skin conditions, such as atopic dermatitis, are linked to microbial dysbiosis, we have only recently identified a direct role for microbes in driving itch. The pathogen Staphylococcus aureus is rarely isolated from healthy skin but can be found in up to 90% of atopic dermatitis lesions. We discovered that S. aureus directly activates itch neurons and triggers scratching behaviors which exacerbate skin barrier damage. Currently, it is not clear how microbes signal through the skin to brain axis during itch and skin inflammation. Our present data shows that S. aureus-induced itch drives responses in the dorsal root ganglia, spinal cord, and brain that are distinct from those observed in nonmicrobial triggers of skin barrier damage, dermatitis, and itch. Dissecting what neural circuits are activated by microbial triggers of itch will further our understanding of how bacteria contribute to the itch-scratch cycle and skin inflammation.
Title: Chronic Pruritus in Older Adults: Epidemiology, Associated Factors, and Impact on Quality Of Life
Juliette Bollemeijer Erasmus University Medical Center, Department of Dermatology, Dr. Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands
Background: Chronic pruritus (CP) is a burdensome condition that frequently affects older adults, yet its epidemiology and impact on quality of life (QoL) in general older populations remain underexplored. Objectives: To determine CP prevalence, identify associated demographic, lifestyle, dermatological, systemic, neurological, medication-related, and psychological factors, and evaluate its impact on pruritus-specific QoL in a large population-based cohort. Methods: This cross-sectional study included participants from the Rotterdam Study who completed questionnaires on current, 12-month, and lifetime CP, and the ItchyQoL. Associations between predefined factors and CP outcomes were assessed using multivariable logistic regression. Associations with pruritus-specific QoL were evaluated using linear regression with ItchyQoL scores. Principal component analysis (PCA) explored the dimensional structure of the ItchyQoL. Results: Among 4474 participants (median age: 72 years; 58.8% female), the prevalence of current, 12-month, and lifetime CP was 8.6%, 10.5%, and 18.6%, respectively. CP was independently associated with female sex, age, smoking, atopic dermatitis, psoriasis, dry skin, asthma, steatotic liver disease, polyneuropathy, depressive symptoms, anxiety, and poor sleep quality. Among those with current CP, pruritus-specific QoL was moderately impaired (median ItchyQoL score: 47). The most pronounced impairments were linked to atopic dermatitis, depressive symptoms, anxiety, and poor sleep quality. PCA revealed four ItchyQoL dimensions—social/emotional impact, psychological distress, lifestyle/environmental burden, and physical symptoms—extending beyond the original three domains. Conclusions: CP is common in older adults and associated with a wide range of dermatological, systemic, neurological, and psychological factors. Atopic dermatitis and psychological symptoms were most strongly linked to impaired pruritus-specific QoL. These findings underscore the need to recognize CP as a clinically significant, heterogeneous condition in ageing populations and to ado
Title: Itch Subcluster Mapping in Human Dorsal Root Ganglia via Single Nucleus RNA-Sequencing
Tyler Beck Vanderbilt University Medical Center
Tyler C. Beck, MD, PhD (1,2), Jordan Morningstar, BS (3,4), Stephano Berto, PhD (5), Shawn Afvari, BS (6), Manuel Valdebran, MD (7), Russell A. Norris, PhD (3,8), Shawn G. Kwatra, MD (9) 1Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA 2Department of Dermatology, Vanderbilt University Medical Center, Nashville, TN, USA 3Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC, USA 4Medical Scientist Training Program, Medical University of South Carolina, Charleston, SC, USA 5Department of Neurosciences, Medical University of South Carolina, Charleston, SC, USA 6College of Medicine, Medical College of New York, Valhalla, NY, USA 7Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina, Charleston, SC, USA 8Department of Neurosurgery, Medical University of South Carolina, Charleston, SC, USA 9Department of Dermatology, University of Maryland, Baltimore, MD, USA
Introduction: Itch is a common and often debilitating sensation associated with dermatological, systemic, and neuropathic disorders, profoundly impacting quality of life. Differentiating the molecular mechanisms underlying itch from those of pain is essential for the development of targeted therapeutics. The dorsal root ganglion (DRG), which transmits peripheral sensory signals to the central nervous system, serves as a key focus for understanding itch signaling and identifying potential drug targets. Objectives: To map human DRG neuronal subclusters associated with itch and pain using single-nucleus RNA sequencing (snRNA-seq) and identify overrepresented pathways that may serve as potential therapeutic targets. Methods: We analyzed a publicly available snRNA-seq dataset of human DRG neurons to identify transcriptomic subclusters. Gene expression profiles were used to classify neurons into functional groups, with a focus on itch-specific clusters. Pathway enrichment analysis and CellChat-based communication network modeling were performed to explore molecular signaling and intercellular communication. Results: Fifteen distinct neuronal clusters were identified, including two itch-specific clusters, H10 and H11. These clusters showed enrichment of pruritus-related genes such as IL31RA, OSMR, JAK1, and OPRM1. Pathway analysis revealed 144 overrepresented biological pathways, including druggable pathways like mTOR, PI3K-Akt, MAPK, TNF, cGMP-PKG, JAK-STAT, serotonergic, glutaminergic, Hippo, and oxytocin signaling. CellChat analysis demonstrated extensive inter-cluster communication, particularly between itch and pain clusters. Conclusion: This study delineates distinct transcriptomic signatures of human itch-specific DRG clusters and highlights key molecular pathways with therapeutic potential. These findings provide a foundation for future drug discovery and repurposing efforts targeting chronic itch.
Title: Molecular Pharmacological Analysis of 15 Psychotropic Drugs in Pruritus Modulation: Implications for Atopic Dermatitis
Koichi Miyakawa Department of Psychiatry, Juntendo University Urayasu Hospital, Chiba, Japan.
Jun Utsumi/Juntendo Itch Research Center (JIRC), Institute for Environmental and Gender-Specific Medicine, Juntendo University Graduate School of Medicine, Chiba, Japan. Mitsutoshi Tominaga/Juntendo Itch Research Center (JIRC), Institute for Environmental and Gender-Specific Medicine, Juntendo University Graduate School of Medicine, Chiba, Japan. Yayoi Kamata/Juntendo Itch Research Center (JIRC), Institute for Environmental and Gender-Specific Medicine, Juntendo University Graduate School of Medicine, Chiba, Japan. Kenji Takamori/Juntendo Itch Research Center (JIRC), Institute for Environmental and Gender-Specific Medicine, Juntendo University Graduate School of Medicine, Chiba, Japan.
Therapeutic indications for prescription drugs are typically established through clinical trials. However, new uses are sometimes identified through analysis of pharmacological activity, a process known as drug repurposing or repositioning. Based on clinical observations that certain psychotropic medications are used to manage pruritus, we investigated their potential application in treating atopic dermatitis through molecular pharmacological profiling, using transcriptomics and bioinformatics. To identify genes related to pruritus, we extracted 434 candidates from an international database of disease-associated genes. Among these, 61 genes were implicated in itch exacerbation through inflammatory responses and signaling pathways, while 40 were associated with skin barrier function. Normal human keratinocytes were individually treated with 15 approved psychotropic drugs, and gene expression changes were assessed using ultra-sensitive microarray-based transcriptomic analysis. Comparing drug-induced expression profiles with the itch-related gene set revealed that several psychotropic agents downregulated genes involved in itch amplification and upregulated those related to skin barrier maintenance. These favourable patterns were observed not only in known antipruritic agents such as κ-opioid receptor agonists but in several other psychotropic drugs. Machine learning visualization (t-SNE) of gene expression profiles supported these trends. These findings suggest that certain psychotropic drugs may simultaneously suppress itch signaling and enhance skin barrier function, offering potential as novel therapeutic options for atopic dermatitis.
Title: Determine the role of itch-responsive neurons projecting from the parabrachial nucleus (PBN) to the central amygdala (CeA) in the itch affective circuit in acute itch and chronic itch models
Darya Pavlenko University of Miami, Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, 1600 NW 10th Ave, Miami, FL 33136
Hirotake Ishida, Anika Markan, Tasuku Akiyama (University of Miami, Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, 1600 NW 10th Ave, Miami, FL 33136)
Introduction: The parabrachial nucleus (PBN) and the central amygdala (CeA) are both involved in itch processing, but the precise neural pathways remain poorly understood due to their heterogeneous cell populations. Within the PBN there is a subpopulation of calcitonin gene-related peptide-positive (CGRP+) neurons that are linked to itch, with their silencing reducing scratching behaviors. The specific projections of these CGRP+ PBN neurons involved in itch have not been identified. Additionally, the role of itch-responsive neurons projecting from the PBN to the CeA has not been investigated previously. Methods/Results: To characterize the itch-responsive neurons, we used a combination of the targeted recombination in active populations (TRAP2) system, retrograde tracing, and immunohistochemistry. First, itch-responsive neurons were captured by pairing an i.p. 4-hydroxytamoxifen injection with an i.d. serotonin injection which induces expression of tdTomato in those cells. Next, cholera toxin subunit B (CT-B), a retrograde tracer, was injected into the CeA. We analyzed the overlap between CGRP+ cells and TRAPped cells, CT-B+ cells and TRAPped cells, and cells that were triple positive. Our analysis revealed that CGRP+ cells were only found in the external lateral area of the PBN. Additionally, only 8% of the CGRP+ cells were TRAPped, and of those, 72% projected to the CeA. Of all the TRAPped cells in the PBN, 17% of them projected to the CeA. Optogenetic activation of itch-responsive PBN–CeA neurons significantly increased spontaneous scratching, but it didn’t alter pruritogen-induced scratching, anxiety-like behaviors, thermal sensitivity, or mechanical sensitivity. Additionally, in an atopic dermatitis-like chronic itch model, inhibiting these itch-responsive neurons significantly reduced scratching bouts, but didn’t change locomotion or anxiety-like behavior. Conclusions: These findings suggest that the itch-related PBN-amygdala pathway comprises heterogeneous neurons with a small percentage being CGRP+ and that this pathway is involved in the itch neural pathway, but not in anxiety or pain.
Title: Identification of a Pruritus-Specific Molecular Signature in Chronic Inflammatory Skin Diseases
Sara Riçku Dept. of Dermatology, University Clinic Duesseldorf, Duesseldorf, Germany.
Peter Olah1, Anna Smola1, Tobias Weihrauch2, the PruSearch Consortium FOR2690 4, Sonja Ständer3, Martin Schmelz4, Ulrike Raap2, Bernhard Homey1 INSTITUTIONS (ALL): 1. Dept. of Dermatology, University Clinic Duesseldorf, Duesseldorf, Germany. 2. Division of Experimental Allergy and Immunodermatology, Carl von Ossietzky Universitat Oldenburg, Oldenburg, NDS, Germany. 3. Department of Dermatology, Universitat Munster, Münster, NRW, Germany. 4. Department of Experimental Pain Research, University of Heidelberg, Mannheim, Germany.
Introduction: Pruritus, or itch, is a prominent symptom of chronic inflammatory skin diseases, such as atopic dermatitis (AD), while it is less frequent and milder in psoriasis (Pso). Despite its clinical relevance, the underlying mechanisms of pruritus remain poorly understood. Objectives: To identify a pruritus-specific gene signature by integrating clinical data, responses to cutaneous electrical stimulations (ES), and RNA sequencing (RNA-seq) data from skin biopsies of patients with AD, Pso, and healthy volunteers (HV). Methods: Clinical data and bulk RNA-sequencing datasets of skin biopsies were collected from patients with AD (n = 61), Pso (n = 50), and HV (n = 17). Firstly, we stratified the AD cohort by transcriptomic severity, identifying a subgroup with heightened inflammation (ADhi). Differential gene expression analysis was conducted comparing ADhi with Pso and HV samples. Functional enrichment analysis of the resulting differentially expressed genes (DEGs) was performed. Additionally, we applied slowly depolarizing cutaneous electrical stimulations (half-sine wave pulses and sinusoidal stimuli) across all participants. Within the AD group, differential expression analysis was performed comparing responders and non-responders to ES, followed by functional enrichment and pathway analysis. Results: We identified DEGs (n = 161) associated with pruritus in AD compared to Pso and HV, which were enriched for several neuronal function-related and inflammatory pathways. During ES, pain was reported by all participants, whereas pruritus was preferentially reported among AD patients, where a subset of responders to ES was determined. Within the AD group, transcriptomic comparisons between responders and non-responders revealed 152 DEGs in lesional and 166 in non-lesional skin, which were enriched for both inflammatory and neuron-related pathways. Conclusion: We defined a pruritus-specific gene signature comprising both established and novel pathways, offering new insights into the molecular mechanisms of itch.
Title: A new activator of Slack potassium channels shows robust efficacy in models of histamine-independent and chronic itch in mice
Achim Schmidtko Goethe-Universität Frankfurt, Institut für Pharmakologie und Klinische Pharmazie, Max-von-Laue-Str. 9, 60438 Frankfurt am Main, Germany
Author/Affiliation: Annika Balzulat, W. Felix Zhu, Victor Hernandez-Olmos, Ewgenij Proschak, Achim Schmidtko Institute of Pharmacology and Clinical Pharmacy and Institute of Pharmaceutical Chemistry, Goethe University, Frankfurt am Main, Germany Introduction: Various disorders are accompanied by histamine-independent itching, which is often resistant to the currently available therapies. Slack (Kcnt1, KNa1.1) is a potassium channel that is highly expressed in itch-sensitive sensory neurons and spinal dorsal horn neurons. Previous studies in knockout mice suggest that Slack controls the neuronal activity in histamine-independent itching. Objectives: In this study, we hypothesized that pharmacological activation of Slack has therapeutic potential for the treatment of histamine-independent and chronic itch. Methods: A series of new compounds was synthesized using linear synthesis routes. The functional activity of the new compounds against human Slack was determined using a FluxOR potassium ion channel assay and patch-clamp recordings in vitro. The in vivo efficacy was analyzed in multiple mouse models of itch induced by chloroquine, SLIGRL, β-alanine, histamine, DNFB or MC903. Whole-cell patch-clamp recordings were conducted on itch-sensitive sensory neurons. Results: Based on the Slack-activating antipsychotic drug, loxapine, we designed a series of new derivatives with improved pharmacodynamic and pharmacokinetic profiles that enabled us to validate Slack as a pharmacological target in vivo. We found that one of the new Slack activators displayed potent on-target antipruritic activity in mouse models of acute histamine-independent itch induced by chloroquine, SLIGRL or β-alanine, and in mouse models of chronic itch induced by DNFB or MC903. Patch-clamp recordings confirmed that the new Slack activator inhibited the activity of itch-sensitive sensory neurons. Conclusion: Our study established Slack activation as a novel pharmacological strategy for the treatment of histamine-independent and chronic itch.
Title: Kappa opioids inhibit spinal circuits to suppress itch
Tayler Sheahan Medical College of Wisconsin
Department of Cell Biology, Neurobiology, and Anatomy
8701 Watertown Plank Rd.
Milwaukee, WI 53226
United States
Itch is a protective sensation that drives scratching. Although specific cell types have been proposed to underlie itch, the neural basis for itch remains unclear. To address this gap in knowledge, we used two-photon Ca2+ imaging of the mouse spinal cord dorsal horn to visualize neuronal populations that are activated by itch-inducing agents. We identified a convergent population of spinal interneurons recruited by diverse itch-causing stimuli that represents a subset of neurons that express the gastrin-releasing peptide receptor (GRPR). Moreover, we found that itch is conveyed to the brain via GRPR-expressing spinal output neurons that target the lateral parabrachial nuclei. We further showed that the kappa opioid receptor agonist nalfurafine relieves itch by selectively inhibiting GRPR spinoparabrachial neurons. These experiments provide a population-level view of the spinal neurons that respond to pruritic stimuli, pinpoint the output neurons that convey itch to the brain, and identify the cellular target of kappa opioid receptor agonists for the inhibition of itch.
Title: Role of the spinal cord in chronic itch
Miho Shiratori-Hayashi Juntendo Itch Research Center (JIRC), Institute for Environmental and Gender Specific Medicine, Juntendo Univ. Graduate school of Medicine, 2-1-1 Tomioka Urayasu-shi, Chiba 279-0021, JAPAN
Mitsutoshi Tominaga/Juntendo Itch Research Center (JIRC), Institute for Environmental and Gender Specific Medicine, Juntendo Univ. Graduate school of Medicine Yoshitoshi Kasuya/Department of Molecular and Systems Pharmacology, Faculty of Pharmacy, Juntendo University Kenji Takamori/Juntendo Itch Research Center (JIRC), Institute for Environmental and Gender Specific Medicine, Juntendo Univ. Graduate school of Medicine Makoto Tsuda/Department of Molecular and Systems Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University
Chronic itch associated with allergic skin inflammation, such as atopic dermatitis, significantly impairs patients' quality of life and requires appropriate treatment. However, since many cases of this condition are resistant to existing treatments, such as antihistamines, understanding the underlying mechanisms is important. Our research focuses on changes in the spinal cord. During our study, we found that astrocytes, which are a type of glial cell in the spinal cord, become activated over a long period during the chronic phase. Cutting the nails of the hind paws suppressed this activation, suggesting a link between astrocyte activation and skin damage or inflammation associated with scratching. Both pharmacological and genetic studies have demonstrated that astrocyte activation depends on the transcription factor STAT3. We identified lipocalin 2 (LCN2), a substance whose expression increases in a STAT3-dependent manner. We discovered that LCN2 contributes to chronic itch by amplifying the gastrin-releasing peptide (GRP) signal in the spinal cord. Furthermore, we clarified that astrocyte STAT3 activation occurs in the long term via IP3R1/TRPC-dependent calcium signaling induced by IL-6, which increases in primary afferent neurons. In addition to astrocyte activation, we recently discovered that neuronal pentraxin 2 (NPTX2), also increased in primary afferent neurons, contributes to chronic itch by enhancing glutamate transmission in spinal itch neurons. These studies have revealed details about the significance of spinal cord changes in chronic itch.
Title: Dissecting the heterogenous keloid microenvironment with spatial technologies
Yingrou Tan National Skin Centre
Immanuel Kwok Weng Han, Shuzhen Chong, Lai Guan Ng, Hong Liang Tey
Keloids are itchy, painful pathological cutaneous scars formed from dysregulated wound healing, resulting in a fibrotic environment where fibroblasts excessively deposit collagen. Current existing therapies such as cryotherapy or intralesional triamcinolone do not fully resolve keloids, hence it is important to understand ongoing pathophysiological processes driving fibrosis to identify potential targets for developing new treatments. Recent single-cell RNA sequencing (scRNAseq) keloid studies have provided insight into fibroblast and vascular endothelial cell dysregulation and cellular crosstalk which could drive disease pathogenesis, although these studies lack spatial insight. To address this, we mapped existing keloidal scRNAseq datasets onto the high-resolution Stereo-seq spatial dataset generated with 2 distinct patient samples, using cryosections from different parts of the keloid. Cell identities were mapped with cell population scRNAseq signatures using Cell2location algorithm, and cellular compartments identified with non-negative matrix factorization (NMF). This approach was validated by the co-localization of lymphatics, endothelium and smooth muscle cells; and separately, keratinocyte populations together with melanocytes. Simultaneously, it revealed spatial niches containing keloidal myofibroblasts with Schwann cells, mast cells and T cells. At the same time, sections were analysed using highly cyclic immunofluorescence staining with MACSima Imaging Cyclic Staining (MICS). Our dataset demonstrates the known extensive vascularisation of the keloid with differential localization of extracellular matrix (ECM) proteins, revealing higher expression of collagen III fibrils which are typically initially expressed during wound healing in the papillary dermis region. This was subsequently replaced by collagen I and fibronectin in the deeper reticular dermis, which makes up a large part of the keloid tissue. Simultaneously, we observed the presence of co-localizing fibroblasts with CD11c+ dendritic cells and endothelium. Together, such spatial maps would allow us to identify cellular interactions responsible for driving pathogenesis.
Title: Deciphering the Role of Periostin in Atopic Dermatitis-Associated Cutaneous Hypersensitivity
Joshua Wheeler Department of Molecular Biomedical Sciences, NC State College of Veterinary Medicine, NC State University, 1060 William Moore Dr. Raleigh, NC, 27607, USA
Santosh K. Mishra; Department of Molecular Biomedical Sciences, NC State College of Veterinary Medicine, NC State University, 1060 William Moore Dr. Raleigh, NC, 27607, USA
Introduction: Itch is a hallmark symptom of atopic dermatitis (AD); however, many patients report other sensations, such as prickling, burning, and numbness, with the inflammation in these atopic dermatitis lesions, which are associated with thermal and mechanical hypersensitivity. Periostin has been demonstrated to be involved in promoting inflammation, in addition to its pruritogenic activities; therefore, we hypothesized that periostin might play a role in modulating pain hypersensitivity in AD lesions. Objectives: We set out to determine if mice treated with MC903, a common mouse model of AD, have altered thermal and mechanical hypersensitivity responses. We also tested if periostin mediates these thermal and mechanical hypersensitivity responses. Finally, we sought to determine if cilengitde, a periostin-receptor antagonist, could be used to reduce AD-associated thermal and mechanical hypersensitivity. Methods: We applied MC903 or Ethanol to the mouse hind paws and then assessed heat hypersensitivity, cold hypersensitivity, pressure responses, and mechanical hypersensitivity of these treated hind paws using the Hargreaves, dry ice, static Upright SHIM, and electronic von Frey assays Periostin (5 µg/ 20 µL) or saline (20 µL) was injected into the plantar surface and thermal and mechanical hypersensitivity was assessed at baseline, 0.5 hr, 2 hr, 4 hr, 8 hr, 12 hr, and 24 hr post injection. We administered cilengitide to determine if antagonism of the periostin receptor reduced thermal and mechanical hypersensitivity in MC903- or periostin-treated mice. Results: We found significant differences in pressure sensation, heat hypersensitivity, and cold hypersensitivity on Day 5 of MC903 application. We found that periostin induces significant heat, cold, and mechanical hypersensitivity in all our assays, which peaked at 0.5 hr or 2 hr post periostin injection. Conclusion: We demonstrate that MC903-treated plantar surfaces have significantly increased thermal and mechanical hypersensitivity, which is mediated by periostin, and that these hypersensitivities can be blocked with cilengitide.
Title: Investigation of the anti-inflammatory, anti-pruritic, and analgesic effects of sophocarpine inhibiting TRP channels in a mouse model of inflammatory itch and pain
Hekun Zeng State Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Huangpu Avenue West 601, Guangzhou, Guangdong, China
Zhe Zhang, Dan Zhou, Ranjing Wang, Alexei Verkhratsky, Hong Nie*.
Sophocarpine is a bioactive compound extracted from the dried root of Sophorae Flavesentis Aiton, a plant that has been used for thousands of years for various conditions including skin itch and pain. Its antipruritic and analgesic effects are suggested in publications, while the molecular mechanisms underneath interacting with TRP channels are not understood. In this article, we investigated the anti-inflammatory, antipruritic, and analgesic effects of sophocarpine in a murine inflammatory itch and pain model to elucidate the underlying mechanisms. First of all, we evaluated sophocarpine’s anti-pruritic and analgesic effects by monitoring mice’s scratching and wiping behaviors, and the anti-inflammatory effect by measuring psoriasis area and severity index (PASI) score. The mRNA and protein expression of TRPA1/TRPV1 was analyzed by real-time quantitative polymerase chain reaction and western blotting. We further investigated the relationship between sophocarpine and TRPA1/TRPV1 in mice administered allyl-isothiocyanate (AITC) or capsaicin and by molecular docking. As a result, we found that sophocarpine decreased scratching bouts, wipes and the PASI score, and reduced the TNF-α and IL-1β in the skin and TRPA1 and TRPV1 in the trigeminal ganglion. Pretreatment of sophocarpine decreased AITC-induced scratching bouts and wipes and capsaicin-induced wipes. We also found potential competitive bindings between sophocarpine and AITC/capsaicin to TRPA1/TRPV1. In conclusion, sophocarpine is a potential competitive inhibitor of TRPA1 and TRPV1 channels eliciting strong anti-inflammatory, anti-pruritic, and analgesic effects, suggesting its significant therapeutic potential in treating diseases with inflammatory itch and pain. Further research should focus on protein pockets identified to testify whether sophocarpine is a better competitive inhibitor of TRPV1 on binding at ARG442 in its S4-S5 linker, compared with capsazepine which may not be a good competitive inhibitor of TRPV1. Furthermore, the competitive binding study on TRPA1 and validation in vivo should be carried out in the future using a more TRPA1-specific agonist than AITC.
Title: Somatic symptom disorder is associated with higher pruritus intensity, stress and reduced quality of life in chronic pruritus: the SOMA.PRU study
Stefan M. Kahnert University Hospital Münster, Department of Psychosomatic Medicine and Psychotherapy, Albert-Schweitzer-Campus 1, 48149 Münster, Germany
Introduction Patients with chronic pruritus (CP) frequently suffer from mental health issues. Somatic symptom disorder (SSD) is a relatively 'new' psychiatriccondition that is defined as excessive thoughts, feelings, or behaviors related to persistent somatic symptoms, such as CP. Studies on SSD in CP are lacking. Objectives To determine the prevalence of SSD in patients with CP as well as to study associations with patient-reported outcomes. Methods Patients with CP in atopic dermatitis or on non-lesional skin were recruited at university departments in Germany. At baseline, participants underwent a structured clinical interview, considered the ‘gold standard’ in psychiatric diagnostics, to diagnose SSD. Participants self-reported average and worst pruritus (AP, WP) in the last 24 hours on a numerical rating scale (range 0 – 10), stress level (Perceived Stress Scale, PSS-10) and pruritus-related quality of life (ItchyQoL). Participants were followed up for 6 months. Results Ninety-five participants could be recruited. Prevalence of SSD was found to be 14.7% (n = 14). At baseline, SSD was associated with higher AP (6.9 (1.8) vs. 5.3 (1.7), p = 0.001) and WP (8.3 (1.2) vs. 7 (1.8), p = 0.003), stress (p = 0.007) and ItchyQol scores in symptoms, functions and emotions (p < 0.001). At follow-up, participants with SSD still reported higher AP (5.7 (2.3) vs. 3.9 (2.3), p = 0.02), WP (7.8 (2.1) vs. 6 (2.8), p = 0.04) and ItchyQoL scores (p = 0.01, p = 0.05 and p = 0.002 resp.). Conclusion In our sample, about one in seven CP patients also suffered from SSD. This comorbidity was associated with a higher pruritus-related burden, both cross-sectionally and longitudinally. Patients with the double burden of CP and SSD might benefit more from an interdisciplinary approach that also includes psychotherapy for SSD. Such interventions should be evaluated in future studies.
Title: Broad Deployment of the ItchyQuant Reveals Disparities in Care Access and Follow-Up in Patients with Itch
Rene Chen Duke University School of Medicine, 40 Duke Medicine Circle, Durham, NC 27710, USA
Introduction Itch is a defining dermatologic symptom with implications for care access. The ItchyQuant is a validated patient-reported outcome measure (PROM) rating itch severity on a 0–10 scale. It is a component of the Standard Dermatology Outcome Measures (SDOM), a panel of five validated PROMs assessing symptoms, treatment, and quality-of-life. Objective We aim to explore how itch severity and systemic or operational barriers affect follow-up after missed dermatology appointments. Methods The ItchyQuant (via SDOM) was distributed to all patients by portal 7 days before any dermatology appointment (excluding Mohs surgery). Appointments associated with patient first-time severity score ≥1 were analyzed after two years. Missed appointments were classified as patient- or clinician-driven. Patient-driven cases were categorized as social determinants of health (SDOH; e.g. transportation)-related or unrelated (e.g. illness). Clinician-driven cases were categorized as preventable (e.g. vacation) or non-preventable (e.g. illness). Follow-up rates and delays were compared by subgroup and itch severity. Results Among 8,907 qualifying responses, 507 were linked to missed appointments. Patients with severe (8-10) itch (n=106) had higher follow-up rates (73.6%) but longer mean delays (68.9 days) compared to those with mild (1-3) itch (n=155; 67.7%, 62.6 days). Of 404 patient-driven missed appointments, 123 were SDOH-related. Within the severe itch group, SDOH-related cases had reduced follow-up (50.0%) and longer delays (112.6 days) versus non-SDOH cases (76.3%, 74.3 days) with a similar trend across severity bands. Among 103 clinician-driven missed appointments, preventable cases (n=49) resulted in longer delays than non-preventable ones (n=53) across all severity bands (e.g., mild: 34.2 vs. 19.7 days; severe: 36.9 vs. 17.4 days) with comparable follow-up rates. Conclusion These findings highlight how SDOH and clinical operations affect care access for patients with itch and how broadly deployed PROMs like the ItchyQuant/SDOM can identify gaps and guide interventions.
Title: Neglected Dimensions: Do Large Language Models Truly Grasp Key Quality-of-Life Concerns in Chronic Itch Management?
Ahmet Uğur Atilan Pamukkale University Faculty of Medicine, Denizli, Turkey
Ahmet Uğur ATILAN* Niyazi ÇETİN* *Pamukkale University Faculty of Medicine, Denizli, Turkey
Introduction:Chronic itch erodes psychological well-being; patients seek not only symptom relief but sustainable control and restored quality of life (QoL). How effectively large language models (LLMs) communicate these multidimensional needs remains unknown.Objectives:To compare four general-purpose LLMs in conveying patient-centred dimensions of life quality and long-term control across diverse chronic-itch scenarios.Methods:Nine vignettes were crafted to capture the spectrum of chronic-itch distress: prurigo nodularis, chronic spontaneous urticaria(CSU), severe paediatric atopic dermatitis, biologic-resistant scalp psoriasis, chronic cutaneous lupus, early-stage mycosis fungoides, prebullous pemphigoid, dialysis-related uremic pruritus and chronic pelvic pain syndrome(CPPS) in men. Each scenario embedded concerns about sleep disruption, work impairment, sexual dysfunction, social avoidance, emotional distress, body-image dissatisfaction, treatment fatigue and stigma. ChatGPT-4, Gemini 2.5 Flash, Claude 4 Sonnet, and LLaMA 4 Scout produced responses. Two blinded clinicians scored outputs on a 5-point Likert scale across five domains:empathy/emotional validation, addressing QoL dimensions, long-term control/expectation management, information quality/safety and patient-centeredness/empowerment. Flesch Reading Ease quantified readability.Results: ChatGPT led in empathy and readability, consistently validating distress and providing calibrated reassurance; Gemini followed. Claude topped information quality and safety, balancing risk–benefit and adding caveats. Claude and ChatGPT referenced emerging therapies, demonstrating currency. QoL dimensions scored lowest across models: sleep disruption, sexual health, occupational impact, and stigma were frequently neglected, especially in prurigo nodularis, pre-bullous pemphigoid, CSU, and CPPPS.Conclusion:While current LLMs show clinical relevance and empathy, they often miss key quality of life elements. Improving patient-centered dermatologic communication will require fine-tuning with QoL data, prompt design, resource retrieval, and expert feedback to create models that address chronic itch with deeper understanding.
Title: The mechanisms of itch contagion and stigmatization: role of behavioral immune activation?
Anastasiia Myronenko Institute of Psychology, Health, Medical and Neuropsychology Unit, Leiden University, the Netherlands
S. van Beugen, PhD / Institute of Psychology, Health, Medical and Neuropsychology Unit, Leiden University, the Netherlands A.I.M. van Laarhoven, PhD/ Institute of Psychology, Health, Medical and Neuropsychology Unit, Leiden University, the Netherlands
Introduction The behavioral immune system (BIS) plays a key role in detecting and avoiding potential sources of pathogens, often triggering behavioral (e.g., avoidance) and emotional (e.g., disgust) responses to disease-relevant cues, facilitating survival. Previous research suggests involvement of BIS in the perception of contagious itch and stigmatization. For example, seeing someone scratch can induce contagious itch as a protective mechanism, while observing visible skin lesions (even from non-infectious conditions) may evoke stigma due to perceived health threat. However, experimental research on the causal role of BIS activation in contagious itch and stigmatization remains limited. Objectives This study examines whether BIS activation, through visual exposure to pathogen-themed information, increases itch contagion and stigmatizing attitudes toward a person with a chronic skin condition. Methods In a video vignette experiment (target N = 136), all participants first viewed a person with psoriasis discussing a neutral topic, with lesions concealed. Then, participants were randomly assigned to watch a BIS-activating (pathogen-themed) or neutral control video. After this, participants watched a third video showing the same person from the first video, but now with visible lesions, scratching, and describing intense itch experiences. Outcomes included subjective itch ratings and stigma-related attitudes and behavioral avoidance (social distance). Results Preliminary results (N = 56) show that participants experienced a significant increase in itch sensations and desire for social distance after viewing the third video when compared to the first video. These effects occurred regardless of prior exposure to the pathogen-themed video, indicating no additive effect of pathogen-themed priming. Conclusion Preliminary results suggest that the combination of visual skin lesions, scratching, and talking about itch elicits both contagious itch and stigmatizing attitudes. While ongoing data collection may further clarify these effects, initial findings suggest that itch contagion and stigmatization are driven by perceptual cues, and not amplified by pathogen-related threat.
Title: The relationship between social anxiety, neuroinflammatory parameters and itch in patients with psoriasis
Marcel Schepko Justus-Liebig-University of Giessen, Department of Medicine, Institute of Medical Psychology, Germany
Eva Peters2, Bernd Hanewald3, Katharina Stumpf1, Jörg Kupfer1, Christina Schut1 1 Justus-Liebig-University of Giessen, Department of Medicine, Institute of Medical Psychology, Germany 2 University Clinic Gießen and Marburg, Clinics for Psychosomatics and Psychotherapy, Germany 3 University Clinic Gießen and Marburg, Clinics for Psychiatry and Psychoherapy, Germany
Introduction: In patients with psoriasis, itch is related to psychological factors like anxiety. Both, anxiety and itch, are related to certain inflammatory parameters like interleukin-6 (IL-6), interleukin-31 (IL-31) and Substance P. To the best of our knowledge no study has investigated whether the relationship between social anxiety – a facet of anxiety – and itch is mediated by these parameters in psoriasis-patients. Objectives: To investigate whether psoriasis-patients and healthy skin controls differ in social anxiety, IL-6, IL-31 and SP and whether the relationship between social anxiety and itch is mediated by these parameters. Methods: The research project has two parts. Study 1 is a questionnaire-study, in which n = 249 psoriasis-patients and n= 246 healthy skin controls were included. Validated questionnaires were used to measure social anxiety. In study 2, in addition to itch and social anxiety, IL-6, IL-17 and SP were determined in suction blister fluid from the skin of n = 31 psoriasis patients and n = 32 healthy skin controls. The blister fluid was derived by use of a suction pump applied to the forearm of the participants. Results: In study 1, itch intensities (average and maximal itch during the last 24 hours) and social anxiety (social interaction anxiety- and social phobia scores) significantly differed between the groups with significantly higher values in patients than controls (p < 0.05). In study 2, no significant group differences were observed regarding social interaction anxiety, social phobia, IL-6, IL-31 or SP (all p > 0.05). Conclusion: Psoriasis-patients reported to be more socially anxious than healthy skin controls (study 1). The suction pump was used as a relatively easy method to assess the neuroinflammatory parameters IL-6, IL-17 and SP in the skin, which however were unrelated to itch and social anxiety in this study (study 2).
Title: Dupilumab for Itch on Prurigo chronica multiformis: a pilot case study
Tsukasa Ugajin Institute of Science Tokyo, Department of Dermatology, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan; Japanese Red Cross Musashino Hospital, Department of Dermatology, 1-26-1 Kyonan-cho, Musashino-shi, Tokyo 180-8610, Japan
Introduction: Prurigo chronica multiformis (PCM) is a subtype of prurigo that has been described in detail in Japan, characterized by intensely itchy urticarial erythema and solid papules. Our previous study revealed that PCM is associated with a more pronounced type 2 inflammation-related blood biomarker profile compared to prurigo nodularis. Objectives: To investigate the clinical efficacy of dupilumab in alleviating itch and skin symptoms of PCM. Methods: We assessed the degree of itch and skin symptoms, as well as biomarkers, including white blood cell count, serum levels of IgE and thymus and activation-regulated chemokine (TARC)/CCL17, and blood basophil activation status measured by CD203c expression, before and after a 6-week dupilumab treatment (at week -4 to 0, week 8, and week 16). Results: Itch and skin symptoms improved shortly after the first dupilumab treatment (week 8); however, in one case, an itch flare occurred 10 weeks after the last administration (week 16). Biomarkers of type 2 inflammation decreased in both cases following the initial treatment, but in the case with recurrent itch, serum TARC level and CD203c expression on basophils returned to baseline by week 16. Conclusion: IL-4/13 signaling is likely involved in the pathogenesis of PCM. Additionally, TARC levels and basophil activation status may be more closely correlated with itch than with skin symptoms in PCM. Further studies on a larger patient cohort are necessary to confirm these findings.
