Poster
P1Title:
Galectin-1,
IGLV1-47 and CD44 Correlate with Pruritus Symptoms in Patients with
Moderate-to-Severe Atopic Dermatitis treated with Dupilumab
Submitting
author:
Agueusop, Inoncent - Sanofi, Frankfurt
Additional
Authors:
Elena Goleva2, Evgeny Berdyshev3, Simion Kreimer4,
Taras Lyubchenko2, Robert Bissonnette5, Emilie Gloaguen6, Joseph
Zahn7, Ana B. Rossi8, Annie Zhang8, Donald Y.M. Leung1 2Department of
Pediatrics, National Jewish Health, Denver, CO, USA; 3Division of
Pulmonary, Critical Care and Sleep Medicine, National Jewish Health,
Denver, CO, USA; 4Advanced Clinical Biosystems Institute, Smidt Heart
institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA;
5Innovaderm Research, Montreal, QC, Canada; 6Sanofi Subcontracting
Soladis, Paris, France; 7Regeneron Pharmaceuticals, Inc., Tarrytown,
NY, USA; 8Sanofi, Cambridge, MA, USA.
Abstract:
Introduction: Chronic pruritus in atopic dermatitis (AD) lesional skin arises from a multifactorial pathogenesis, prominently involving type 2 immune responses. Disruption of the epidermal barrier facilitates the translocation of plasma proteins such as fibrinogen, fibronectin, Galectin 1, IGLV1-47 and CD44 into the epidermis. The presence of plasma proteins in lesional skin may contribute to the pathophysiology of itch. For instance, Staphylococcus aureus, a bacterium implicated in chronic pruritus, can bind to host proteins such as fibronectin and fibrinogen, potentially exacerbating inflammatory responses and itch sensation Objectives: To report new potential itch biomarkers and the effect of dupilumab treatment on these biomarkers. Methods BALISTAD (NCT04447417) was a 16-week study in patients with AD aged 12–65 years. Serial skin assessments with skin tape stripping (STS) were performed on lesional and non-lesional AD skin of patients treated with dupilumab and on the normal skin of healthy volunteers. Proteomic analysis on STS protein extracts were performed by liquid chromatography tandem mass spectrometry at Day 1, Day 56, and Week 16. Results: Strong correlations were detected between PP-NRS score at baseline and Galectin-1 (0.74), IGLV1-47 (0.71) and CD44 (0.78). Moderate correlation detected between PP-NRS at baseline and fibrinogen gamma (0.38), fibrinogen beta (0.45), fibrinogen alpha (0.24) and fibronectin (0.21). Galectin-1 (p<0.0001), IGLV1-47 (p<0.0001), CD44 (p<0.0001), fibrinogen(s) (p<0.0001), fibronectin (p<0.0001) and PP-NRS score (<0.0001) decreased significantly from baseline to week16. Safety was consistent with the known dupilumab safety profile. Conclusions: Dupilumab significantly decreased expression levels of biomarkers strongly correlated with chronic pruritus in patients with AD, to levels comparable with those of healthy controls, and improved patient symptoms. The biomarkers could be further investigated as new itch biomarkers, which could drive research into new therapies for chronic pruritus.
P2
Title:
Prevalence
of itch in patients with diabetic neuropathy with and without pain
Submitting
author:
Arendt-Nielsen, Lars - Center for Neuroplasticity and
Pain (CNAP), Department of Health Science and Technology, School of
Medicine, Aalborg University & University Hospital
Additional
Authors:
Mette Krabsmark Borbjerg, Steno Diabetes Center North
Denmark, Aalborg University Hospital, Aalborg University, Aalborg,
Denmark Anne-Marie Wegeberg, Steno Diabetes Center North Denmark,
Aalborg University Hospital, Department of Clinical Medicine, Aalborg
University, Aalborg, Denmark Amar Nikontovic, Steno Diabetes Center
North Denmark, Aalborg University Hospital, Aalborg, Denmark Carsten
Dahl Mørch, Center for Neuroplasticity and Pain (CNAP), Aalborg
University, Integrative Neuroscience, Aalborg University, Aalborg,
Denmark Niels Ejskjaer, Steno Diabetes Center North Denmark,
Department of Endocrinology, Aalborg University Hospital, Department
of Clinical Medicine, Aalborg University Aalborg, Denmark Christina
Brock, Mech-Sense, Aalborg University Hospital, Department of
Clinical Medicine, Aalborg University, Aalborg, Denmark Peter
Vestergaard, Steno Diabetes Center North Denmark, Aalborg University
Hospital, Department of Endocrinology, Aalborg Univer
Abstract:
Background: Diabetic peripheral neuropathy (DPN) and neuropathic pain impacts Quality of Life (QoL) and mental health negatively. Up to 50% of people with diabetes experience morbidities such as neuropathic pain but also itch. Itch has been an underrecognised symptom in DPN and hence untreated which leads to further impact on QoL. Aim: In a cross-sectional survey to 1) elucidate the associations between painful and painless DPN and QoL and 2) assess the associated prevalences of symptomatic itch. Methods: Participants were grouped into people with (n=1,601) and without (n=5,359) DPN based on the Michigan Neuropathy Screening Instrument questionnaire. Participants with DPN were subsequently divided into people with (n=1,085) and without (n=516) concomitant neuropathic pain based on the modified Douleur Neuropathique en 4 Questions-interview. In these populations QoL and the prevalence of itch was evaluated. Results: The study showed diminished QoL (SF36: 55.1 [IQR 36.7, 73.6], p-value < 0.001) in participants with DPN compared to participants without DPN. The addition of pain further diminished QoL (SF36: 50.7 [IQR 34.8, 69.8] p-value < 0.001). The most prevalent pain descriptor in participants with painful DPN were burning pain (73%), while the most prevalent sensory descriptor was pins-and-needles (93%). The prevalence of itch was 44% in the cohort with painful DPN and 7% in the population without pain. The QoL in patients with painful DPN itch was further reduced (SF36: 45.75 [IQR 31.92, 64.75], p-value < 0.001) Conclusions: Itch in diabetes has been an underestimated focus in the clinic and hence the high prevalence call for action in relation to recognition and management.
P3
Title:
Dupilumab
Consistently Reduced Itch Severity in Patients With Chronic
Spontaneous Urticaria Across Baseline Characteristic Subgroups in a
LIBERTY-CSU CUPID A and C Pooled Analysis
Submitting
author:
Casale, Thomas - Division of Allergy and Immunology,
University of South Florida, 13220 USF Laurel Drive, Tampa, FL, USA
Additional
Authors:
Sarbjit S. Saini2, Gil Yosipovitch3, Moshe
Ben-Shoshan4, Ana M. Giménez-Arnau5, Koremasa Hayama6, Joseph Zahn7,
Tayler Gonzalez8, Sonya Cyr7, Philip Sugerman8, Allen Radin7, Melanie
Makhija8 2Johns Hopkins Asthma and Allergy Center, Baltimore, MD,
USA; 3Dr. Phillip Frost Department of Dermatology and Cutaneous
Surgery and Miami Itch Center, University of Miami, Miami, FL, USA;
4McGill University Health Centre, Montreal, QC, Canada; 5Hospital del
Mar Research Institute, Universitat Pompeu Fabra, Barcelona, Spain;
6Nihon University School of Medicine, Tokyo, Japan; 7Regeneron
Pharmaceuticals Inc., Tarrytown, NY, USA; 8Sanofi, Cambridge, MA, USA
Abstract:
Introduction: Demographic factors and disease characteristics may impact therapeutic response in patients with chronic spontaneous urticaria (CSU). Dupilumab, an interleukin 4/13 inhibitor, improved itch and hives in LIBERTY-CSU CUPID (NCT04180488) Studies A and C. Objectives: To assess itch reduction with dupilumab across CSU patient subgroups based on age, gender, body mass index (BMI), and angioedema status. Methods: Omalizumab-naive patients (aged 6–80 years; CSU diagnosis >6 months before screening; itch/hives >6 weeks despite H1-antihistamine treatment; 7-day Urticaria Activity Score ≥16; 7-day Itch Severity Score [ISS7] ≥8) were randomized in two replicate, 24-week, placebo-controlled, double-blind, phase 3 studies (CUPID A and C). In this analysis (placebo/dupilumab, n=145/144), subgroups were defined by baseline BMI, angioedema status, gender, and age. Itch improvement was assessed by LS mean change from baseline in ISS7 (range 0–21). Results: Mean age of dupilumab- and placebo-receiving patients was 43.2 and 43.0 years, respectively, 61.1% and 75.2% were female, and 54.9% and 59.3% were White. Week 24 ISS7 improvement was greater with dupilumab treatment vs placebo across subgroups; treatment by subgroup interactions were non-significant (P > 0.05). The improvement with dupilumab (–10.35; –9.01; –10.15) was consistently greater than with placebo (–6.27; –6.70; –6.57) irrespective of baseline BMI (<25 kg/m2; ≥25 to <30 kg/m2; ≥30 kg/m2). Similar improvement was observed across patients with/without angioedema at baseline with dupilumab (–8.77/–11.17) vs placebo (–6.13/–7.53). For females and males, dupilumab reduced itch (–9.64 and –10.88) more than placebo (–6.27 and –7.88). Similarly, in patients aged <65/≥65 years, improvement was greater with dupilumab (–9.90/–10.69) compared with placebo (–6.77/–8.21). Safety was generally consistent with the known dupilumab safety profile. Conclusion: Dupilumab consistently reduced Week 24 itch severity across patient subgroups regardless of age, gender, BMI, or presence of angioedema.
P4
Title:
Improvement
in the severity of atopic dermatitis and associated pruritus through
complementary modulation of pruritogenic and inflammatory pathways.
Submitting
author:
Fabrice, Lestienne - Pierre Fabre Dermo-Cosmetics &
Personal Care, R&D Center, Toulouse, FRANCE
Abstract:
Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by erythema, severe dryness, and itching. It is associated with a compromised skin barrier, type 2 inflammation, and pruritogenic markers. Emollients are recommended to restore the skin barrier and alleviate itching. This study aims to understand how to modulate various AD parameters, including the skin barrier, inflammation, and pruritus, and demonstrate the efficacy of an emollient cream containing Rhealba® Oat and Helichrysum extracts. An open clinical study was conducted on 21 women with mild to moderate AD, with a 7-day period without product application followed by 28 days of daily cream application. Clinical evaluations focused on AD severity and pruritus. Samples were collected for lipidome analysis. In vitro studies assessed the anti-inflammatory and anti-pruritogenic properties of the extracts, using keratinocyte models in a Th2 context, inhibition of IL-8 and TSLP release, modulation of JAK pathway phosphorylation, and a sensory neuron/keratinocyte co-culture model. Post-treatment, a significant increase in long-chain ceramide and acyl-ceramide synthesis, and a reduction in short-chain ceramides were observed, strengthening the skin barrier. The emollient cream significantly reduced two bioactive lipids involved in pruritus and inflammation: 15-HEPE and 13-HODE, while increasing pro-resolving lipids. Clinically, this translated into significant improvements in AD severity (-53.2%), pruritus (-74.1%), and sleep disturbances (-85.6%). Patients perceived a decrease in pain and stress related to pruritus. In vitro studies showed that the extracts reduced TSLP and IL-8 release, and inhibited STAT6 phosphorylation. They also inhibited Brain Natriuretic Peptide (BNP) production and neuronal sprouting in an IL-31 stimulated sensory neuron-keratinocyte model. These results demonstrate the link between action on AD regulatory mechanisms and clinical signs evolution, highlighting the potential benefits of these extracts in an emollient for managing moderate AD and associated pruritus.
P5
Title:
A
Therapeutic Challenge: Managing Coexisting Chronic Prurigo and
Psoriasis with Upadacitinib.
Submitting
author:
Gruber, Viktoria - University Clinic of Dermatology and
Venereology, Medical University of Graz, Auenbruggerplatz 8, 8036
Graz, Austria
Additional
Authors:
Gruber V., Riegler M., Sauseng C., Schirl C.,
Schadelbauer E., Weger W., Legat F. J.
Abstract:
Introduction
Chronic prurigo (CPG) is a dermatosis characterized by intensely pruritic, symmetrically distributed papules, nodules, plaques, ulcerated/umbilicated lesions or linear lesions. Its exact pathogenesis remains unclear. CPG frequently coexists with systemic diseases and dermatologic conditions such as atopic dermatitis and psoriasis.
Objectives
We report a case of a 46-year-old male with concomitant CPG and plaque psoriasis treated at the Department of Dermatology, Medical University of Graz.
Methods
The patient had a long-standing history of psoriasiform lesions affecting the body, face, genitals, and nails since 2007, without clinical signs of psoriatic arthritis. His medical history included arterial hypertension, hyperlipidemia, and chronic nicotine use. Additionally, in 2020, he developed intensely pruritic, hyperpigmented papules, nodules and ulcerated/umbilicated lesions on the upper and subsequently lower extremities, histologically confirmed as prurigo.
A comprehensive diagnostic workup was performed. Routine lab results were unremarkable except for elevated lipid levels. Serologic tests for HIV and hepatitis were negative. Indirect immunofluorescence testing revealed no abnormalities. Imaging studies provided no significant findings.
Psoriasis had been insufficiently treated with topical corticosteroids and vitamin d analoga. Initial systemic treatment with Ixekizumab led to a significant improvement in psoriatic lesions, but had no impact on CPG or pruritus. A subsequent trial with Dupilumab led to worsening of both conditions and was discontinued. Ustekinumab then achieved complete clearance of psoriatic lesions; however, CPG persisted.
Results
Due to persistent severe pruritus (ppNRS 9/10), off-label treatment with Upadacitinib 15 mg/day was initiated. After eight weeks, there was a near-complete resolution of prurigo lesions and a marked reduction in pruritus (ppNRS 1/10). Psoriatic lesions remained in remission, and no adverse effects were observed.
Conclusion
No systemic therapy is currently approved for the treatment of both CPG and plaque psoriasis. Upadacitinib, a selective JAK1 inhibitor, which is already licensed for the treatment of inflammatory conditions such as psoriatic arthritis, may offer a promising dual-targeted approach due to its effects on both Th2 and Th17 inflammation. Therefore, it could represent a valuable option for patients suffering from both CPG and psoriatic conditions.
P6
Title:
Exploring
Non-Pharmacological Approaches on Rapid Itch Relief: A Pilot Study
Submitting
author:
Hua, Wei - West China Hospital, Sichuan University,
Department of Dermatology & Venerology, No.37 Guoxue Alley,
Chengdu City, Sichuan Province, PR China
Abstract:
Introduction: Pruritus, an unpleasant sensation provoking scratch, often leads to an "itch-scratch cycle" that compromises skin integrity. Rapid itch relief is crucial for patients. Despite clinical advice to use non-pharmacological methods, robust research on their immediate efficacy for acute itch is notably lacking. Objectives: This pilot study aimed to evaluate the immediate efficacy of various non-pharmacological interventions in rapidly alleviating experimentally induced pruritus in healthy individuals, comparing temperature applications, tactile stimulation, and topical hydration on itch intensity and duration. Methods: Twenty-seven healthy participants underwent cowhage-induced pruritus in five marked forearm areas. Interventions were randomly applied for one minute: 15°C application, ice pack, moisturizer, gentle stroking, or blank control. Itch intensity was assessed via Visual Analog Scale (VAS) immediately post-intervention and at subsequent time points. Primary outcomes were immediate itch relief percentage and overall itch duration. Results: Following cowhage, itch peaked at 2 minutes (mean VAS: 71.28 ± 16.87). All four interventions significantly relieved itch compared to the blank control (Kruskal-Wallis, Bonferroni corrected). Median (IQR) itch relief percentages were: 15°C (43.75% [36.67%]), ice pack (53.33% [50.00%]), moisturizer (22.22% [30.00%]), and stroking (33.33% [19.78%]). Low-temperature interventions provided significantly greater relief than moisturizer; ice pack was significantly more effective than stroking. No significant difference was found in overall itch duration. However, six ice pack and two 15°C participants experienced itch recurrence, and ten ice pack participants reported pain. Conclusion: All four non-pharmacological interventions offered short-term itch improvement. Low-temperature interventions were more effective, but presented potential adverse effects like pain and itch recurrence.
P8
Title:
Evaluation
of peripheral mechanisms of pruritus in neurofibromatosis type 1
Submitting
author:
Imai, Satoko - Department of Dermatology, The Jikei
University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku,
Tokyo 105-8461, Japan
Abstract:
Author/Affiliation Satoko Imai, Yozo Ishiuji, Minako Ogawa-Tominaga, Michie Katsuta, and Akihiko Asahina Department of Dermatology, The Jikei University School of Medicine, Tokyo, Japan Introduction: Chronic pruritus is a common and debilitating symptom in patients with neurofibromatosis type 1 (NF1), significantly compromising quality of life. Despite its clinical relevance, the pathophysiological mechanisms underlying NF1-associated itch remain elusive, and no standardized therapeutic strategies have been established. Objectives: This study aimed to elucidate the pathogenesis of NF1-related itch by investigating peripheral nerve fiber morphological abnormality, mast cell distribution within cutaneous neurofibromas, and the involvement of interleukin-31 (IL-31), a key pruritogenic cytokine. In addition, pruritus hypersensitivity was evaluated using mechanical alloknesis. Methods: We conducted behavioral testing for alloknesis, immunohistochemical staining to assess mast cell infiltration, and fluorescent immunostaining to evaluate peripheral nerve fiber structure and IL-31 expression in cutaneous neurofibromas. Results: Our findings revealed no marked abnormalities in epidermal nerve morphology and IL-31 expression levels were comparable between pruritic and non-pruritic lesions. Similarly, no significant differences in alloknesis thresholds were observed. Although mast cell density was elevated in neurofibromas overall, no clear correlation with pruritic symptoms was established, highlighting the necessity for expanded case analysis. Conclusion: Collectively, these results indicate that the itch mechanism in NF1 diverges from the inflammatory pathways implicated in atopic dermatitis or prurigo nodularis. While IL-31 and peripheral nerve alterations appear unlikely to be central drivers, the observed mast cell enrichment suggests a potential contributory role. Further investigations focusing on mast cell activation and signaling may unveil novel therapeutic avenues for managing NF1-associated pruritus.
P9
Title:
Unusual
Itching in an Infant: A Rare Manifestation of Infantile Tremor
Syndrome
Submitting
author:
Jain, Jinisha - Department of Dermatology Venerology and
Leprosy
JNMC, KLE Belgaum
India
Additional
Authors:
Jinisha Anand Jain
Abstract:
Affiliation - JNMC, KLE Belgaum, India
Introduction
The skin often reflects underlying systemic illness, enabling early diagnosis. In infants, pallor, pigmentary changes with itching, hypotonia, and tremors can point toward Infantile Tremor Syndrome (ITS)—a clinical condition seen in exclusively breastfed infants of economically disadvantaged vegetarian mothers. Not all patients show the full spectrum of symptoms, and mild or atypical features may lead to underdiagnosis. While itching is not a classic manifestation, vitamin B12 deficiency may cause itching and burning sensations, possibly explaining intractable crying in some infants. Prompt recognition is crucial, as timely treatment can reverse symptoms and improve outcomes.
Case Report
A sixteen-month-old girl presented with patterned hyperpigmentation over flexural areas for two months and persistent crying. She was exclusively breastfed and had a history of right foot tremors. No fever or recent infections were noted. Examination revealed lethargy, irritability, mucosal pallor, and diffuse reticular hyperpigmentation over the limbs, trunk, and axillae. Linear excoriations and papules were seen on the extremities. Hair was sparse, brownish, and lusterless. The child had developmental regression of six months and signs of moderate acute malnutrition. Blood tests showed macrocytic hypochromic anemia (Hb 10.3 g/dL, MCV 117 fL) and low serum vitamin B12 (85.67 pg/mL). A diagnosis of ITS was made. Treatment included cyanocobalamin, calcium-vitamin D3, zinc, and oral vitamin A. At 4 weeks, hyperpigmentation was fading, and developmental milestones showed improvement.
Conclusion
ITS is a reversible neuro-nutritional disorder with a prevalence of 0.7–2.5%, often accompanied by megaloblastic anemia. Though rare, itching and burning sensations due to vitamin B12 deficiency may explain crying and scratch marks in affected infants. Early diagnosis and appropriate supplementation are key to preventing long-term neurodevelopmental deficits.
P10
Title:
Characteristics
of Pruritus in Various Clinical Variants of Psoriasis Based on the
Binational, Multicenter, Cross-Sectional Study
Submitting
author:
Jaworecka, Kamila - Department of Dermatology,
University of Rzeszow, Rzeszow, Poland
Additional
Authors:
Adam Reich, Dominika Kwiatkowska, Luiza
Marek-Jozefowicz, Funda Tamer, Aleksandra Stefaniak, Magdalena
Szczegielniak, Joanna Chojnacka-Purpurowicz, Ayla Gulekon, Jacek
Szepietowski, Joanna Narbutt, Agnieszka Owczarczyk-Saczonek
Abstract:
Introduction: Pruritus, which is the most common subjective symptom of psoriasis, can cause significant discomfort, embarrassment, and even interfere with patients’ normal daily activities. However, the perception of itch in various psoriasis subtypes remains unknown. Objectives: The aim of this study was to investigate and characterize pruritus in different clinical variants of psoriasis. Methods: In this cross-sectional, bi-national, multicentre study, 295 subjects suffering from 9 different clinical subtypes of psoriasis were included: large-plaque psoriasis (n=45), small-plaque psoriasis (n=32), guttate psoriasis (n=31), scalp psoriasis (n=32), inverse psoriasis (n=23), erythrodermic psoriasis (n=33), palmoplantar psoriasis (n=33), palmoplantar pustular psoriasis (n=42) and generalized pustular psoriasis (n=23). Measurements included sociodemographic and anthropometric data, detailed characteristics of pruritus, including but not limited to pruritus intensity, frequency, and extend, and psoriasis severity. Results: The lifetime prevalence of pruritus in the different variants of psoriasis was similar and quite high, reaching up to 100% in some disease subtypes (i.e. small-plaque psoriasis, scalp psoriasis and generalized pustular psoriasis). Psoriasis severity correlated with pruritus intensity in scalp psoriasis, palmoplantar pustular psoriasis and generalized pustular psoriasis. Age, duration of psoriasis and BMI had no effect on pruritus intensity. Conclusions: Pruritus is highly prevalent in every clinical variant of psoriasis. However, the sensation of itch is highly individual, difficult to describe universally even in the same subtype.
P11
Title:
Secondary
Burden of Itch: A Study on Family Quality of Life in Chronic Pruritus
and Prurigo Nodularis
Submitting
author:
Kaczmarska-Such, Agnieszka - Dermatology Department
University Clinical Hospital of Rzeszów, Poland
Additional
Authors:
Adam Reich Dermatology Department University Clinical
Hospital of Rzeszów
Abstract:
Intorduction: Chronic pruritus (CP), defined as itch that persists for more than six weeks, presents significant challenges to patients’ physical, psychological, and social well-being, substantially impairing their quality of life. Prurigo nodularis (PN) is characterized by multiple hyperkeratotic nodules and persistent, therapy-resistant itch. While the burden of CP and PN on affected individuals is well recognized, their indirect effects on caregivers and family members have received limited scientific attention. The Family Dermatology Life Quality Index (FDLQI) is a validated instrument designed to measure the quality of life in relatives of dermatology patients, but its application in the context of CP and PN has not yet been systematically studied. Objectives: The primary objective of this study is to assess the quality of life of family members of adult patients with CP or PN using the FDLQI. The secondary objective is to compare FDLQI with patient-reported outcomes, including itch severity (NRS), dermatology-specific quality of life (DLQI), and itch-specific impact (ItchyQoL), and to identify clinical factors associated with greater family impact. Methods: This multicenter, cross-sectional observational study will involve approximately 500 adult patients diagnosed with CP or PN, along with one adult family member or informal caregiver per patient. Patients will complete the DLQI, ItchyQoL, NRS, and a clinical-demographic questionnaire capturing disease duration and treatment history. Family members will complete the FDLQI and a short supplemental questionnaire assessing time spent on care, occupational consequences, and psychosocial burden. Expected Results: We hypothesize that higher NRS scores, longer disease duration, and increased caregiving time will be significantly associated with higher FDLQI scores. Patients with PN are expected to be associated with greater secondary burden compared to those with non-nodular CP. During the congress pilot results of the study will be presented. Conclusion: We hope that these findings may help to develop family-centered strategies in dermatologic care and contribute to a more comprehensive understanding of CP.
P13
Title:
A
Retrospective Cohort Study on the Efficacy of Pregabalin in Patients
with Sensitive Skin
Submitting
author:
Kim, Hye One - Department of Dermatology, Hallym
University Kangnam Sacred Heart Hospital, Hallym University, 948-1,
Daerim-1-Dong, Yeongdeungpo-gu, Seoul 150-950, Republic of Korea
Abstract:
Sensitive Skin Syndrome (SSS) is a complex dermatological disorder marked by abnormal sensations in response to harmless stimuli, with no established therapies specifically targeting neural sensitization. This retrospective cohort study assessed the effectiveness of pregabalin in 112 SSS patients (10.8% male, 89.2% female; mean age 40.5 ± 13.1 years) who received 25–150 mg/day over a period of up to 25 weeks. The primary endpoint was the change in Sensitive Skin-10 (SS-10) scores at 12 weeks, with responders defined as those achieving a ≥30% reduction. After 12 weeks of treatment, 46.4% of patients were classified as responders. Higher baseline SS-10 scores strongly predicted better treatment response (r = 0.5, P < 0.001), with patients having SS-10 ≥50 showing significantly higher response rates compared to those with milder symptoms (56.7% vs. 36.8%, P = 0.003). Symptom-specific predictors of favourable response included tingling sensations (adjusted OR = 1.25, 95% CI: 1.00–1.56, P = 0.050), whilst generalised discomfort predicted poorer outcomes (adjusted OR = 0.53, 95% CI: 0.34–0.83, P = 0.005). Significant correlations were observed between SS-10 scores and DLQI (r = 0.49, P < 0.001) and HADS (r = 0.29, P = 0.002). Von Frey threshold measurements revealed a significant negative correlation with symptom severity (r = -0.28, P = 0.008), providing objective evidence for altered somatosensory processing. Quantitative facial erythema analysis demonstrated significant those who are required correlations with subjective symptom severity among treatment responders (r = 0.39, P = 0.009), with temporal stability of this neurovascular coupling maintained throughout treatment. Pregabalin reduced symptoms in sensitive skin syndrome, particularly in patients with severe, neuropathic-like sensations. Novel quantitative erythema assessment showed stable neurovascular coupling with symptom improvement. These findings support the neurogenic hypothesis of sensitive skin and suggest that pregabalin may represent a valuable therapeutic option for this challenging condition.
P14
Title:
Analysis
of independent itch and lesion responders in dupilumab treated
patients
Submitting
author:
Kim, Brian - Icahn School of Medicine at Mount Sinai,
New York, NY, USA
Additional
Authors:
Sonja Stander2, Raj Chovatiya3,4, Amy H. Præstgaard5,
Joseph Zahn6, Simmi Wiggins7 2University Hospital Münster, Münster,
Germany; 3Chicago Medical School, Rosalind Franklin University of
Medicine and Science, North Chicago, IL, USA; 4Center for Medical
Dermatology + Immunology Research, Chicago, IL, USA; 5Sanofi,
Cambridge, MA, USA; 6Regeneron Pharmaceuticals Inc., Tarrytown, NY,
USA; 7Sanofi, Reading, UK
Abstract:
Introduction: Prurigo nodularis (PN) is a chronic inflammatory disease that profoundly impacts quality of life. A fundamental unanswered question in PN pathophysiology is whether itch relief directly translates into the resolution of PN lesions (i.e., clear skin) and whether the mechanisms underlying both processes are strongly correlated or can operate independently. Objective: To explore the dependencies and independencies of itch and nodule clearance in PN. Methods: LIBERTY-PN PRIME (NCT04183335) and PRIME2 (NCT04202679) were randomized, double-blind, 24-week, phase 3 trials of dupilumab in adult patients with moderate-to-severe PN. Patients were randomized to dupilumab 300 mg every 2 weeks or matched placebo, for 24 weeks. In this pooled analysis, dupilumab treated patients were assessed for: ≥4-point reduction in Worst Itch Numeric Rating Scale (WI-NRS) and an Investigator’s Global Assessment of PN Stage of 0 or 1 (IGA PN-S); and stratified by those achieving either, or both endpoints at week 24. Results: Of the 311 adult patients in the pooled PRIME/PRIME2 studies, 148 dupilumab treated patients were stratified by their improvements in skin itch and/or lesion clearance. 37.8% of these patients achieved both IGA PN-S 0/1 and ≥4-point improvement in WI-NRS, while 27.7% achieved ≥4-point improvement in WI-NRS only, and 12.2% achieved IGA PN-S 0/1 only. Of those achieving a concomitant itch improvement and lesion clearance response, 33.9% achieved an IGA PN-S score of 0, while 66.1% achieved an IGA PN-S score of 1. Overall safety was generally consistent with the known safety profile of dupilumab. Conclusions: A subset of dupilumab treated patients achieved independent responses of either itch relief or lesion clearance, suggesting that dupilumab may act on both components of disease, possibly by independent mechanisms. This finding indicates that further research is required to elucidate these mechanisms and their interactions on nodules beyond simply itch resolution.
P15
Title:
Attenuation,
Near Resolution, and Prevention of Pruritus in Patients With Primary
Biliary Cholangitis Treated With Seladelpar: A Secondary Analysis of
Patterns of Pruritus Change in the RESPONSE Trial
Submitting
author:
Kremer, Andreas E. - Department of Gastroenterology and
Hepatology, University Hospital Zürich, University of Zürich,
Zürich, Switzerland
Abstract:
Introduction: Pruritus in primary biliary cholangitis (PBC) is debilitating and lacks effective treatments. In the Phase 3 RESPONSE trial (NCT04620733), seladelpar (selective PPAR-delta agonist) significantly reduced pruritus in patients with PBC with moderate to severe pruritus (numerical rating scale [NRS] ≥4 at baseline) vs placebo. Objectives: Here, we further evaluated pruritus in RESPONSE. Methods: Patients with PBC and an inadequate response or intolerance to ursodeoxycholic acid, with ALP ≥1.67 × ULN and total bilirubin ≤2 × ULN, received daily, oral seladelpar 10 mg or placebo (2:1) for 12 months (M). We assessed change in pruritus using various improvement thresholds (≥3-/≥4-point NRS reductions, near resolution [NRS ≤1]) in patients with NRS ≥4 or NRS ≥7 (severe itch) at baseline. Development of pruritus in patients without itch (NRS=0) at baseline and safety by baseline NRS (≥4 or <4) were also evaluated. Results: 72/193 enrolled patients had baseline NRS ≥4 (49 seladelpar, 23 placebo); 16 seladelpar and 12 placebo patients had NRS ≥7. Among patients with NRS ≥4, seladelpar reduced mean itch intensity from moderate to mild from 3–12M; itch remained moderate with placebo. For patients with NRS ≥4, 46.9% on seladelpar had a ≥3-point NRS decrease vs 21.7% on placebo (12M); a ≥4-point NRS decrease occurred in 30.6% of seladelpar and 8.7% of placebo patients. More patients with baseline NRS ≥4 (26.5%) or NRS ≥7 (18.8%) on seladelpar experienced near resolution of itch (12M) vs 0% on placebo. In patients without itch at baseline, 26.7% (4/15) on placebo reported pruritus at 12M vs 0% (0/30) on seladelpar. Adverse events occurred in 88.9% (NRS ≥4) and 84.3% (NRS <4) of patients. Conclusion: Seladelpar durably reduced pruritus severity in patients with PBC, led to near resolution of itch in some, mitigated new onset of itch in those without pruritus, and was well tolerated.
P16
Title:
Change
in Pruritus in Patients With Primary Biliary Cholangitis and Moderate
to Severe Pruritus: A Pooled Analysis From the RESPONSE and ENHANCE
Studies David E. J. Jones1, Cynthia Levy2, Andreas E. Kremer3, Alma
Ladron de Guevara Cetina4, Alejandra M. Vi
Submitting
author:
Kremer, Andreas E. - Department of Gastroenterology and
Hepatology, University Hospital Zürich, University of Zürich,
Zürich, Switzerland
Abstract:
Introduction: Pruritus in primary biliary cholangitis (PBC) can greatly reduce quality of life. In two Phase 3, placebo-controlled trials (ENHANCE [NCT03602560], RESPONSE [NCT04620733]), seladelpar (selective PPAR-delta agonist) significantly reduced pruritus among patients with PBC with moderate to severe pruritus (MSP) at baseline (numerical rating scale [NRS] ≥4). Objectives: Here, we present pooled pruritus outcomes across different measures of itch in patients with PBC from RESPONSE and ENHANCE with NRS ≥4 at baseline. Methods: Patients with PBC and an inadequate response or intolerance to ursodeoxycholic acid received daily, oral seladelpar 5 mg, seladelpar 10 mg, or placebo (ENHANCE: 1:1:1 randomization; 52 weeks) and seladelpar 10 mg or placebo (RESPONSE: 2:1 randomization; 52 weeks); ENHANCE was terminated early with key endpoints amended to 3 months (M). Pooled data from patients with NRS ≥4 at baseline receiving seladelpar 10 mg or placebo in RESPONSE and ≥6M in ENHANCE were analyzed. Changes in NRS, PBC-40 itch domain, and 5-D itch scale up to 6M were assessed post hoc. Results: Of 126 patients with NRS ≥4, 76 and 50 received seladelpar 10 mg or placebo in RESPONSE and ENHANCE. Itch scale scores were similar between treatment groups at baseline. At 6M, patients receiving seladelpar experienced greater improvements in NRS (mean change from baseline [CFB] −3.12 vs −2.09, seladelpar vs placebo, P=.0004), PBC-40 itch domain (mean CFB −2.26 vs −1.37, P=.0227), 5-D itch total (mean CFB −4.85 vs −2.30, P<.0001), and 5-D itch degree domain (mean CFB −0.96 vs −0.54, P=.0005). Safety profiles for patients with pruritus were similar across treatment groups in this pooled analysis. Adverse events occurred in 58/76 (76.3%) seladelpar and 40/50 (80%) placebo patients. Conclusions: Up to 6M of seladelpar treatment reduced pruritus vs placebo in patients with PBC and MSP across 3 measures of itch. Seladelpar was well tolerated.
P17
Title:
Linerixibat
significantly improves cholestatic pruritus in primary biliary
cholangitis (PBC): Results of the pivotal Phase 3 GLISTEN trial
Submitting
author:
Kremer, Andreas - Department of Gastroenterology and
Hepatology, University Hospital Zurich, University of Zurich, Zurich,
Switzerland
Additional
Authors:
G.M. Hirschfield(1), C.L. Bowlus(2), D.E.J. Jones(3),
M.J. Mayo(4), A. Tanaka(5), P. Andreone(6), J. Jia(7), Q. Jin(8),
R.U. Macías-Rodríguez(9), A.R. Cobitz(10), B.M. Currie(10), C.
Gorey(11), I. Lazic(11), D. Podmore(11), A. Ribeiro(12), J.B.
Shannon(13), B. Swift(13), M.M. McLaughlin(10), and C. Levy(14)
(1)University Health Network, Toronto General Hospital, Canada;
(2)University of California Davis School of Medicine, Sacramento, US;
(3)Newcastle University, UK; (4)University of Texas Southwestern
Medical School, Dallas, US; (5)Teikyo University School of Medicine,
Japan; (6)Azienda Ospedaliero-Universitaria di Modena and Università
di Modena e Reggio Emilia, Italy; (7)Beijing Friendship Hospital,
Capital Medical University, China; (8)The First Hospital of Jilin
University, China; (9)Instituto Nacional de Ciencias Médicas y
Nutrición Salvador Zubirán, Mexico; (10)GSK, Collegeville, US;
(11)GSK, London, UK; (12)GSK, Madrid, Spain; (13)GSK, Durham, US;
(14) University of Miami, US.
Abstract:
Introduction: Cholestatic pruritus is common and debilitating in patients with PBC. Objectives: The double-blind, randomised Phase 3 GLISTEN (NCT04950127) study investigated efficacy and safety of linerixibat for pruritus in PBC. Methods: Patients with PBC and moderate-to-severe pruritus received oral linerixibat 40 mg/placebo twice daily. Primary endpoint: worst itch change from baseline over 24 weeks (pruritus severity assessed using 0–10 numerical rating scale). Secondary endpoints included: change in worst itch (Week 2); change in sleep interference (over 24 weeks); proportion of responders (≥2-, ≥3-, ≥4-point reduction in worst itch; Week 24); responses to patient global impression items. Results: In 238 randomised patients (95% female), itch severity was mean (SD) 7.34 (1.54). Pruritus improvement over 24 weeks was significantly greater with linerixibat than placebo: least-squares (LS) mean change −2.86 versus −2.15 (adjusted mean difference −0.72; p=0.001); at Week 24, pruritus mean (SD) difference from baseline was −3.66 (2.50) versus −2.82 (2.32); at Week 2, LS mean change was −1.78 versus −1.07 (adjusted mean difference −0.71; p<0.001). Linerixibat improved pruritus-related sleep interference over 24 weeks versus placebo: LS mean change −2.77 versus −2.24 (adjusted mean difference −0.53; p=0.024). At Week 24, more patients on linerixibat than placebo achieved a ≥2-point (68% vs 64%), ≥3-point (56% vs 43%) or ≥4-point (41% vs 29%) pruritus reduction and reported pruritus as very much improved (55% vs 37%) or absent (21% vs 9%). AEs reported more frequently with linerixibat than placebo were predominantly gastrointestinal, including diarrhoea (61% vs 18%) and abdominal pain (18% vs 3%); 4% of patients discontinued linerixibat due to diarrhoea. Conclusion: In patients with PBC and moderate-to-severe pruritus, linerixibat rapidly and significantly improved pruritus and pruritus-related sleep interference versus placebo. Gastrointestinal AEs were more common with linerixibat than placebo but rarely led to treatment discontinuation. Funding: GSK [212620]. Previously presented: EASL 2025 (GS-011).
P19
Title:
Dupilumab
- Efficacy and treatment satisfaction in patients with atopic
dermatitis (AD)
Submitting
author:
Liutkevych, Kateryna - Department of Dermatology and
Venereology, Medical University of Graz, Graz, Austria
Abstract:
Introduction Since 2017, dupilumab has helped to relieve symptoms and provided long-lasting improvements in quality of life (QoL), sleep, and itch in patients with AD. This single-center study aimed to assess the long-term clinical efficacy of dupilumab in moderate-to-severe AD patients and to investigate its impact on patients’ long-term QoL and satisfaction with the therapy under real-life conditions. Objective: Analyze long-term clinical efficacy of dupilumab, reduction in clinical scores (WI-NRS, AI-NRS, IGA), and treatment satisfaction. Methods A retrospective analysis of data collected between 01/2017 and 02/2024 from 142 cases was conducted - 3 time points were analyzed: baseline, after 3 months, and after one year of therapy. A prospective online questionnaire gathered feedback from 85 patients regarding relief of the symptoms, side effects, form of administration, and failed injections. Results Retrospective - after one year of therapy: - the mean WI-NRS reduction was 4.9 (p<0.01, 95% CI). - the mean AI-NRS reduction was 3.9 (p<0.01, 95% CI). - the mean IGA reduction was 1.8 (p<0.01, 95% CI), - in 33.3% IGA of 0 or 1, and in 43.3% IGA 2 was achieved. - EASI-75 achieved 60% of the patients. - Side effects: conjunctivitis: 25%, local reactions: 13%, herpes: 10%, other infections: 12%. - No side effects: in 26%. - Drug adherence: 3 months – 93%, 1 year – 86%, [after 5 years: 77% were still on treatment] In the prospective part of the study: - substantial improvement in symptoms: 79%; - substantial improvement in QoL: 73%; - substantial improvement of pruritus: 70%; - substantial improvement of sleep: 70%; - excellent tolerance of the drug: 63%; - very easy handling: 49%. Conclusion: In line with current literature, dupilumab shows excellent long-term clinical efficacy, high patient satisfaction, and a significant improvement in QoL in our patients.
P20
Title:
Pain and
sting intensities provoked at the site of Lebrikizumab (IL-13
inhibitor) injection and the effect of lebrikizumab on experimentally
histamine and non-histaminergic provoked itch sensitization in
healthy volunteers.
Submitting
author:
Markussen, Botilla - Center for Neuroplasticity and
Pain, School of Medicine, Aalborg University and Aalborg University
Hospital, Aalborg, Denmark
Additional
Authors:
S. Lo Vecchio1, G.E. Aliotta1, J. Elberling3,4, L.
Arendt-Nielsen1,2,5 1 Department of Health Science and Technology,
School of Medicine, Aalborg University, Aalborg, Denmark 2 Department
of Gastroenterology & Hepatology, Mech-Sense, Clinical Institute,
Aalborg University Hospital, Aalborg, Denmark 3 Department of
Dermatology and Allergy, Herlev and Gentofte Hospital, Herlev,
Denmark 4 Department of Clinical Medicine, University of Copenhagen,
Copenhagen, Denmark 5 Steno Diabetes Center North Denmark, Clinical
Institute, Aalborg University Hospital, Aalborg, Aalborg, Denmark
Abstract:
Human IL-13 monoclonal antibodies, such as Lebrikizumab can be used as a model compound to investigate the effect of the IL-13 signaling pathways in human sensory processing such as experimentally induced itch and itch related sensitization (alloknesis or hyperknesis). Aim: To evaluate 1) the pain and sting intensity at the site of 3 subsequent Lebrikizumab injections (baseline (500 mg), week 2 (500 mg), week 4 (250 mg)) and 2) the effect of Lebrikizumab on experimentally induced histamine and non-histaminergic itch sensitisation. Methods: Histaminergic and non-histaminergic (cowhage and BAM8-22) itch were used for itch provocations of 3 selected areas on the volar forearm. Itch intensity was assessed for 9 minutes. Mechanically Evoked Itch (MEI) was used for assessing hyperknesis on a 10 points Numerical Rating Scale (NRS), 1 cm away from the area of itch provocation (and from a reference area) by 3 individual vonFrey hairs, and the average itch NRS was calculated. At the end of the session at baseline, week 2 and 4, volunteers received the subsequent subcutaneous injections of Lebrikizumab and the pain and stinging intensities at the sites of injection were assessed on a 10 points NRS. Results: Pain at the injection site was low at baseline (4.1 ± 2.3) and decreased significantly by week 2 (3.3 ± 2.5) and 4 (2.9 ± 2.3) (p<0.001). No changes were found for injection-related stinging which remained low (3.5). MEI after histamine application at week 2, 4, and 6 decreased at week 2 (0.9 ± 0.6, p = 0.014) and week 6 (1.1 ± 1.1, p = 0.040) as compared with baseline (1.5 ± 1.0). No significant changes were found in MEI after non-histaminergic provocations. Conclusions: The pain intensity at the site of Lebrikizumab injections was low and further reduced during the subsequent injections. Lebrikizumab reduced histamine evoked alloknesis.
P21
Title:
Pooled
REMIX-1/-2 Phase 3 Data: Early and Sustained Symptom Improvement With
Remibrutinib in Chronic Spontaneous Urticaria
Submitting
author:
Metz, Martin - 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 Alle
Additional
Authors:
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
Abstract:
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.
P22
Title:
Trial in
Progress: A Phase 2, Randomized, Double-Blind, Placebo-Controlled
Study to Assess the Efficacy and Safety of Barzolvolimab in Patients
with Prurigo Nodularis (PN)
Submitting
author:
Metz, Martin - Institute of Allergology, Charité –
Universitätsmedizin Berlin, corporate member of Freie Universität
Berlin and Humboldt-Universität zu Berlin, Berlin, Germany;
Fraunhofer Institute for Translational Medicine and Pharmacology
ITMP, Immunology and Allergo
Abstract:
Background: Barzolvolimab (CDX-0159), a monoclonal antibody that binds KIT (a receptor tyrosine kinase), inhibits activation by stem cell factor (SCF). KIT is expressed by a variety of cell types including mast cells (MCs). In MCs, KIT activated by SCF potentiates degranulation, regulates survival and chemotaxis. Emerging science supports the role of MCs in chronic pruritus by reciprocal activation between cutaneous MCs and sensory nerves and recruitment of other immune cells. In a Phase 1b study (NCT04944862), 23 participants with PN received a single intravenous dose of barzolvolimab or placebo. Treatment-emergent adverse events were reported in 40.0% of barzolvolimab participants and 62.5% of placebo. At Week 8, barzolvolimab 3.0 mg/kg participants showed 46.1% mean reduction in Worst Itch Numeric Rating Scale (WI-NRS), with 57.1% achieving a ≥4-point reduction, vs 29.7% and 25.0% for placebo, respectively. Investigator global assessment (IGA) of 0/1 was achieved by 29% for barzolvolimab 3.0 mg/kg and 0% for placebo. Efficacy correlated with sustained serum tryptase reduction, a MC activation biomarker. Methods: This Phase 2 study evaluates efficacy (utilizing WI-NRS and IGA-chronic nodular prurigo stage [IGA-CNPG S] to measure primary and key secondary outcomes) and safety of two subcutaneous dose levels (150 mg or 300 mg every 4 weeks [Q4W] for 20 weeks, both with 450 mg loading doses) of barzolvolimab in adult participants with PN (NCT06366750); it also includes an optional, open-label extension (450 mg loading dose and 300 mg Q4W for 20 weeks). Patients with an IGA score ≥3, WI-NRS ≥7 and inadequate response to topical corticosteroids are eligible. Patient reported outcomes include worst itch and pain, sleep quality and disturbance, fatigue, disease severity, and quality of life. IGA-chronic prurigo activity (IGA-CPG A) and prurigo activity score (PAS) are also assessed, along with serum tryptase. Enrollment is open in the USA, Canada, Germany, Spain and Poland.
P23
Title:
Improving
standard of care in chemotherapy – the influence of
active-containing Urea formulations on QoL and skin condition
Submitting
author:
Mießner, Hendrik - Beiersdorf AG, Research &
Development, Hamburg, Germany
Additional
Authors:
Christoph Ernst (Beiersdorf AG, Research &
Development, Hamburg, Germany) Tanja Bußmann (Beiersdorf AG, Medical
Management, Hamburg, Germany) Tim Friemauth (Beiersdorf AG, Research
& Development, Hamburg, Germany)
Abstract:
Introduction Annually, around 20 million new cancer cases are reported, with over 50% of patients undergoing chemotherapy. Two-thirds of these experience skin reactions, including inflamed, itchy patches, dryness, and redness. Such skin changes can worsen the physical burden of cancer, affect quality of life, and lead to therapy interruptions. Objective This study evaluates the effects of urea-containing active formulations on skin condition and dermatological quality of life in chemotherapy patients. Methods A monocentric, randomized, controlled trial involved 65 participants (ages 41-84) undergoing chemotherapy for various cancers (e.g. ductal/bronchial/rectal/colon or pancreatic carcinoma). Participants were divided into two groups: one using an active formulation (10% urea body lotion, 5% urea hand cream, and 10% urea foot cream) and the other using standard of care urea formulations of their choice. Both groups received identical medical information from oncologists. Formulations were applied at least twice daily for nine weeks, with assessments at baseline, 3, 6, and 9 weeks. Skin condition was evaluated through expert clinical grading and self-assessment using validated questionnaires (DLQI, Skindex-16). Results The active formulations demonstrated excellent skin tolerance on body, hands and feet throughout the study. Over 80% of subjects using the active formulations showed improved or unchanged skin condition, with significantly more participants reporting improvements compared to the standard of care group at all assessment points. The active formulations effectively prevented clinically relevant declines in skin-associated quality of life, as indicated by DLQI and Skindex-16 scores. Overall, 100/100/93% (body/hand/feet) of participants claimed the active formulations were ideally suited alongside chemotherapy and provided them with adequate care. Conclusion The active urea formulations exhibited excellent skin tolerance and are well-suited for adjunctive care during chemotherapy. They effectively protect the skin and prevent deterioration in quality of life, highlighting the importance of targeted skincare in enhancing the well-being of cancer patients.
P24
Title:
Long
term observations of a German cohort of individuals affected by
Atopic Dermatitis: opportunities using the handheld IoT device Skinly
Submitting
author:
Mießner, Hendrik - Beiersdorf AG, Research &
Development, Hamburg, Germany
Additional
Authors:
Tanja Bußmann (main author; Beiersdorf AG, Medical
Management, Hamburg, Germany) Tim Ole Sonntag (Beiersdorf AG,
Research & Development, Hamburg, Germany) Maria Bonilla Tobar
(Beiersdorf AG, Research & Development, Hamburg, Germany) Sven
Clemann (Beiersdorf AG, Research & Development, Hamburg, Germany)
Sören Jaspers (Beiersdorf AG, Research & Development, Hamburg,
Germany)
Abstract:
Introduction Advancements in artificial intelligence and at-home analysis devices have revolutionized skin diagnostics. The Skinly device leverages machine learning and advanced imaging technology for non-invasive, real-time skin analysis, enabling users to assess various skin parameters, including skin age, evenness, tone, redness, porphyrin fluorescence, and hydration. Objective This study focuses on tracking self-reported Atopic Dermatitis (AD) patients within the German Skinly collective to understand the long-term progression of AD and evaluate the effects of a dermocosmetic intervention. Methods Data was collected from over 5000 individuals (ages 18-75) in Germany, predominantly female, who self-reported their skin conditions. The study included an observational trial of a dermocosmetic intervention from January to March 2025, where participants used a moisturizing formulation with anti-inflammatory actives twice daily for 8 weeks. Data included self-assessments, biophysical skin measurements, and geospatial information. Results As of 2023, 4.5% of Skinly users reported having AD, with ~25% experiencing moderate to severe symptoms in 2024. Among 124 users tracked for 12 months, there was significant variability in symptom severity. Additionally, 127 users participated in the dermocosmetic intervention, reporting improved skin comfort and reduced AD symptoms, highlighting the intervention's effectiveness. Conclusion The Skinly device is a valuable tool for documenting skin conditions like atopic dermatitis in a home setting. The data collected offers insights into subjective skin assessments and physiological measurements, suggesting that integrating such tools in clinical trials could enhance understanding and management of atopic dermatitis.
P25
Title:
A
randomized, double-blind, placebo-controlled study of monoclonal
Anti-IgE antibody Omalizumab in the management of pruritus in chronic
spontaneous urticaria in the pediatric population
Submitting
author:
Mitra, Debdeep - Department of Dermatology Command
Hospital Chandimandir India 134107
Abstract:
Chronic spontaneous urticaria (CSU) is defined as the spontaneous appearance of itchy wheals, with or without angioedema, persisting for ≥6 weeks. It affects 0.5–1 % of the global pediatric population, but it represents a high burden to patients. Children in the age group of 6 to 12 years present frequently with episodic pruritic wheals and oral anti-histamnics are mostly insufficient to prevent a recurrence. Oral steroids and other immune-suppressives although effective temporarily, are associated with a lot of side effects in this age group and are mostly contraindicated. In recent years, monoclonal Anti-IgE antibody ‘omalizumab’ has been tried in other allergic disorders like atopic dermatitis and bronchial asthma in the pediatric age group, however there are no studies till date of this novel therapeutic regimen in the pediatric age group to control the itching in chronic spontaneous urticaria in the pediatric age group. This study sought to evaluate the efficacy and safety of monoclonal Anti-IgE antibody omalizumab in patients between the group of 6 to 12 years with moderate-to-severe chronic idiopathic urticaria who remained symptomatic despite H1-antihistamine therapy (licensed doses). This was a double-blind, placebo-controlled trial with children between the age group of 6 to 12 years randomized to omalizumab or placebo. Randomly assigned 30 children with comparable baseline age and serum IgE levels received four subcutaneous injections, spaced 4 weeks apart, of omalizumab at a dose of 150 mg or placebo, followed by a 16-week observation period. Mean Urticaria activity score (UAS) at baseline was 5.7 points (range, 4–6 points). Compared with placebo, omalizumab resulted in a statistically significant reduction in FcεRI expression on basophils and pDC2 (P < .001). UAS and serum IgE levels were significantly reduced in the Omalizumab group as compared to the placebo group both at 16 and 32 weeks. Thus, omalizumab is an effective and well-tolerated add-on therapy for children with CSU who are symptomatic despite background therapy with H1 antihistamines.
P27
Title:
Ponesimod
Improves Symptoms of Itch, Soreness, Pain, and Stinging in
Moderate-to-Severe Chronic Plaque Psoriasis
Submitting
author:
Polymeropoulos, Vasilios - Vanda Pharmaceuticals, Inc.
2200 Pennsylvania Ave NW Suite 300E, Washington, DC 20037, USA
Abstract:
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.
P28
Title:
Aquagenic
Urticaria Unmasked by Secondary Polycythemia: A Diagnostic and
Therapeutic Challenge.
Submitting
author:
Rathi, Parth - Department of Dermatology, VMMC &
Safdarjung Hospital, New Delhi, India.
Abstract:
Background: Aquagenic urticaria is a rare physical urticaria often misdiagnosed as chronic spontaneous urticaria (CSU). Secondary polycythemia, commonly from chronic hypoxia, may complicate diagnosis. This case highlights the importance of re-evaluating atypical presentations and the diagnostic value of detailed history and systemic evaluation in dermatologic cases. Case Presentation: A 55-year-old man initially diagnosed with CSU reported dizziness and persistent urticaria. Closer history revealed water-triggered symptoms, confirming aquagenic urticaria. Physical exam also noted dermatographism. He had a history of smoking, hypertension (on amlodipine), and alcohol use. Labs showed hemoglobin 19.7 g/dL, hematocrit 105%, and mildly elevated bilirubin. Bone marrow biopsy and molecular tests (BCR-ABL, CALR, JAK2 exon 12) were negative, indicating secondary erythrocytosis. Diagnosis: secondary polycythemia from smoking-induced hypoxemia. Treatment included phlebotomy, hydroxyurea, and antihistamines. Hemoglobin normalized after smoking cessation; urticaria persisted mildly and was managed with hydroxyzine. Discussion: This case demonstrates a rare overlap of aquagenic urticaria and secondary polycythemia likely due to hypoxia. Though it initially resembled CSU, targeted history clarified the diagnosis. Despite alarming labs, secondary erythrocytosis may reverse with lifestyle changes. Dermatographism added complexity. The patient improved significantly after addressing the underlying hypoxemia. Conclusion: Persistent or atypical urticaria with systemic findings like erythrocytosis warrants diagnostic reassessment. Aquagenic urticaria can mimic CSU and coexist with systemic issues. Thorough history and treating the root cause—here, smoking-related hypoxemia—can normalize systemic parameters and improve skin symptoms.
P29
Title:
Long-term
efficacy and safety of nemolizumab in adolescents with
moderate-to-severe atopic dermatitis: Post hoc analyses from ARCADIA
LTE 1-year cut-off
Submitting
author:
Reich, Adam - Department of Dermatology, University of
Rzeszów, Rzeszów, Poland
Additional
Authors:
Marie Tauber/ Department of Allergy and Clinical
Immunology, Lyon Sud Hospital, Hospices Civils de Lyon, Inserm U1111
Centre International de Recherche en Infectiology, Lyon, France Dedee
Murrell/ Department of Dermatology, University of New South Wales,
Sydney, NSW, Australia Franz J. Legat/ Department of Dermatology and
Venereology, Medical University of Graz, Graz, Austria Andreas
Wollenberg/ Department of Dermatology and Allergy, Augsburg
University Hospital, Augsburg, Germany William Abramovits/
Dermatology Treatment and Research Center, Dallas, TX, USA Antonio
Costanzo/ Department of Dermatology, Humanitas University Medical
School, Rozzano, Italy Liliana Ulianov/ Galderma R&D, Zug,
Switzerland Anna Ryzhkova/ Galderma R&D, Zug, Switzerland Soo
Yeon Cheong/ Galderma Laboratories, Dallas, TX, USA Christophe
Piketty/ Galderma R&D, Zug, Switzerland
Abstract:
Introduction: Nemolizumab, a first-in-class interleukin-31 receptor alpha antagonist, has demonstrated continuous improvements in itch, skin lesions and sleep in adolescent population with moderate-to-severe atopic dermatitis (AD) up to week (W)16. Objectives: This analysis evaluates the efficacy of nemolizumab in adolescent patients with moderate-to-severe AD up to W56 in the long-term extension study. Methods: This prospective, multicentre, open-label, long-term study (NCT03989206) enrolled nemolizumab-previously experienced (NPE), nemolizumab-naïve (NN) patients from ARCADIA 1&2 phase 3 and other nemolizumab studies, along with 37 newly recruited adolescents. Here, we present interim efficacy and safety data at W56 in adolescent patients (12-17 years old) administered nemolizumab 30mg subcutaneously every 4 weeks (Q4W) with concomitant background topical corticosteroids (TCS) of low/medium potency with/without topical calcineurin inhibitors (TCI). Efficacy assessments include proportion of patients with Investigator’s Global assessment (IGA) score of 0/1 (clear/almost clear), ≥75% and ≥90% improvement in the Eczema Area and Severity Index (EASI-75 and EASI-90) from initial baseline, improvement in visual analogue scale (VAS, 0-10) Pruritus and Sleep loss of SCORing Atopic Dermatitis (SCORAD) score and Dermatology Life Quality Index (DLQI) score. All efficacy analyses are summarised using observed data. Results: At data cut-off, 248 adolescents (NPE=141, NN=107; mean age=15 years) were analyzed in the study. At W56, 72% (NPE) and 53% (NN) patients achieved an IGA 0/1 score; 86%, 80% reached EASI-75; 72%, 57% achieved EASI-90; 79%, 59% reported ≥4-point improvement in SCORAD VAS Pruritus; and 64%, 38% achieved VAS score <2, respectively. Improvements in sleep mirrored those in itch (85%, 41%). DLQI score improved over time in ≥87% patients. Most treatment-emergent adverse events were non-serious and mild/moderate in severity. Conclusion: Overall, nemolizumab 30 mg Q4W with TCS/TCI improved key signs and symptoms of AD - pruritus, skin lesions and sleep disturbance in adolescent patients with moderate-to-severe AD during W56 follow-up.
P30
Title:
Evaluation
of the Antipruritic and Anti-Inflammatory Effects of Topical
Ketamine, Amitriptyline and Their Combination on Histaminergic and
Nonhistaminergic Itch
Submitting
author:
Riboldi, Benedetta - Department of Pharmacological and
Biomolecular Sciences “Rodolfo Paoletti”, Università degli Studi
di Milano, Milan, Italy; Department of Health Science and Technology,
School of Medicine, Aalborg University, Aalborg, Denmark
Additional
Authors:
R.Tanaka1,2, G.E.Aliotta1, S.Lo Vecchio1,
J.Elberling3,4, L.Arendt-Nielsen1,5,6 1Dep of Health Science and
Technology, School of Medicine, Aalborg University 2Dep of
Anesthesiology and Resuscitology, Shinshu University School of
Medicine, Matsumoto 3Dep of Dermatology and Allergy, Herlev and
Gentofte Hospital 4Dep of Clinical Medicine, University of Copenhagen
5Dep of Gastroenterology & Hepatology, Aalborg University
Hospital 6Steno Diabetes Center North Denmark, Aalborg University
Hospital
Abstract:
Background: Ketamine has demonstrated antipruritic effects in addition to its well-established analgesic properties, primarily through NMDA receptor antagonism. Topical amitriptyline may enhance these effects by blocking voltage-gated sodium channels, reducing nociceptive transmission. Aim: To evaluate topical ketamine effect on histaminergic and nonhistaminergic itch and whether amitriptyline could enhance its effects. Methods: Four squared areas on the forearms of 23 participants were treated for 1½ hours with ketamine, amitriptyline, ketamine+amitriptyline, and vehicle creams, followed by histamine and cowhage application to induce histaminergic and non-histaminergic itch, respectively. Itch intensity was assessed using a visual analogue scale (VAS) for 10 minutes, followed by measurement of Full-field Laser Perfusion Imaging (FLPI), superficial blood perfusion (SBP), mechanical and thermal sensitivities. From VAS data, peak and area under the curve (AUC) values have been extracted. From FLPI data, mean and peak of SBP, and the flare area have been extracted. Results: Cowhage-induced itch intensity was higher than histamine-induced itch (p<0.001). In the case of the former pruritogen, the combination of ketamine+amitriptyline significantly reduced itch intensity compared to the vehicle cream (peak: p<0.05; AUC: p<0.05), while only a trend was observed in the case of the latter. The combination of ketamine+amitriptyline significantly reduced the flare area, the SBP mean, and the wheal diameter compared to ketamine alone (flare: p<0.05; mean: p<0.01; wheal: p<0.01) and vehicle cream (flare: p<0.001; mean: p<0.01). Interestingly, amitriptyline alone was more effective in reducing SBP compared to ketamine alone (flare: p<0.01), suggesting that the anti-inflammatory effect of the ketamine+amitriptyline combination may be primarily attributed to amitriptyline. No differences in mechanical and thermal sensitivity induced by either pruritogen were observed across the four areas and after cream application. Conclusions: We demonstrated the antipruritic effect of ketamine in combination with amitriptyline, whereas the anti-inflammatory effect appears to be more significant
P31
Title:
Effectiveness
of Tildrakizumab on Treatment Satisfaction and Patient-Perceived
Benefits in an Austrian Cohort with Itchy Plaque Psoriasis
Submitting
author:
Sator, Paul-Gunther - Department of Dermatology, Klinik
Hietzing, Vienna, Austria
Abstract:
Paul-Gunther Sator1, Roxana Pirker1, Lejla Ramic1 1 Department of Dermatology, Klinik Hietzing, Vienna, Austria. Introduction: Itching affects 60–90% of patients with plaque psoriasis and can significantly impair health-related quality of life (HRQoL). Alleviating itch is among the most important treatment goals for patients. Tildrakizumab, an interleukin-23p19 inhibitor, is approved for the treatment of moderate-to-severe plaque psoriasis and has demonstrated long-term efficacy and safety. Objectives: This analysis aimed to evaluate treatment satisfaction and patient-perceived benefits of tildrakizumab therapy in patients with itchy plaque psoriasis under real-world conditions. Methods: This was a monocentric, prospective, non-interventional, post-authorization observational study conducted at a single site in Austria over 28 weeks. Itch severity was assessed using the Numeric Rating Scale (NRS, 0–10) at each visit. Treatment satisfaction was measured using the Treatment Satisfaction Questionnaire for Medication (TSQM-9), and patient-perceived benefit was evaluated using the Patient Benefit Index (PBI). Results: Thirty patients were enrolled (50.0% male; mean age 45.5 ± 15 years). Mean itch NRS scores decreased from 7.5 ± 1.81 at baseline to 3.31 ± 2.51 at week 4 and 0.62 ± 1.37 at week 28. At week 28, TSQM-9 scores were 79 ± 25.8 for effectiveness, 85.1 ± 15.8 for convenience, and 83.6 ± 13.6 for global satisfaction. 70 % patients rated 'very' on item 1 of PBI — indicating a strong desire to reduce physical symptoms such as itch — 65.4% achieved this benefit by week 28. The overall PBI score reached 3.16 ± 0.86 (scale 0–4), indicating a high level of perceived benefit. Conclusion: In a real-world clinical setting, tildrakizumab provided rapid and substantial itch relief, along with high treatment satisfaction and meaningful patient-perceived benefits by week 28.
P32
Title:
Eye
movement desensitization and reprocessing (EMDR) to treat chronic
pruritus – two case reports
Submitting
author:
Schwale, Chrysovalandis - University Hospital and
University of Basel, Department of Psychosomatic Medicine, Basel,
Switzerland
Additional
Authors:
Chrysovalandis Schwale1,2, Eva Loos 2,3, Simon Müller3,
Rainer Schaefert2‡ and Christoph Nikendei 1‡ 1Heidelberg
University Hospital, Department of General Internal Medicine and
Psychosomatics, Section of Psychotraumatology, Heidelberg, Germany
and 2University Hospital and University of Basel, Department of
Psychosomatic Medicine, Basel, Switzerland; 3 University Hospital and
University of Basel, Department of Dermatology, Basel, Switzerland
Abstract:
Chronic pruritus is a hallmark of many dermatoses and is difficult to treat. Eye Movement Desensitisation and Reprocessing (EMDR) is a well-established treatment for psychological trauma and is increasingly being used for other indications such as chronic pain. Our case reports investigate the efficacy of EMDR in the treatment of chronic pruritus at the individual case level. Two psychosomatic-psychotherapeutic inpatients with dermatological comorbidities and chronic pruritus were treated with the standard EMDR protocol over a period of eight weeks at the Department of General Internal Medicine and Psychosomatics, University Hospital of Heidelberg, Germany. One patient had complex post-traumatic stress disorder, a recurrent depressive disorder and psoriasis, while the other had depression, agoraphobia and atopic dermatitis. The treatment consisted of eight weekly 60-minute sessions. Treatment efficacy was assessed using a visual analogue scale (VAS) for pruritus and established questionnaires. Both patients showed a significant improvement in pruritus, with a reduction from 9.5/10 and 8/10 to 0/10 after eight weeks. At 1.5 and 2 year follow-up, pruritus remained at 0-2 on the VAS. These findings suggest that EMDR may be a viable treatment for CP. However, the limitations of case reports highlight the need for larger, systematic and multidisciplinary studies to validate these findings.
P33
Title:
Absolute
itch and quality of life response with lebrikizumab through 52 weeks
Submitting
author:
Serra, Esther - Department of Dermatology, Hospital de
la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona,
Barcelona, Spain
Additional
Authors:
Esther Serra 1, Diamant Thaçi 2, Lluis Puig 1, Kim
Papp 3, Linda Stein Gold 4, Pablo Fernández-Peñas 5, Yu-Huei Huang
6, Andrew Blauvelt 7, Bruce Strober 8, Martin Dossenbach 9, Meritxell
Falqués 10, Laia Bardolet 10, Christian Vestergaard 11 1 Dermatol.
Dep., Santa Creu i Sant Pau Hosp., Barcelona Autonomous Univ., Spain;
2 Institute and Comprehensive Center for Inflamm. Medicine, Lübeck
Univ., Germany; 3 Alliance Clinical Research & Probity Medical
Research, Waterloo; Dermatol. Div, Medicine Dep., Toronto Univ.,
Canada; 4 Henry Ford Health System, Detroit, USA; 5 Dermatol. Dep.,
Westmead Hosp., Sydney Medical School, Sydney Univ., Australia; 6
Dermatol. Dep., Chang Gung Memorial Hosp., Linkou Branch & School
of Medicine, Chang Gung Univ., Taiwan; 7 Blauvelt Consulting, LLC,
Lake Oswego, USA; 8 Dermatol. Dep., Yale Univ. School of Medicine,
New Haven, USA; 9 Eli Lilly & Company, Indianapolis, USA; 10
Almirall, Barcelona, Spain; 11 Dermatol. & Venerol. Dep., Aarhus
Univ. Hosp., Denmark
Abstract:
Introduction: Lebrikizumab (LEB) is a monoclonal antibody for moderate-to-severe atopic dermatitis (AD) that binds with high affinity to interleukin-13. Pruritus is the most frequent symptom of AD and may impact patient quality of life (QoL). Moreover, the attainment of absolute endpoints is clinically relevant and provides additional information to patients and physicians of the remaining amount of disease. Objectives: To report the efficacy of LEB in terms of achieving Dermatology Life Quality Index (DLQI) ≤5 (indicative of a minimal effect on patient’s QoL) and Pruritus-Numeric Rating Scale (NRS) ≤4 (indicative of mild pruritus) at W52 among W16 responders in the ADvocate1&2 trials. Methods: ADvocate1&2 were two identically designed, randomized, placebo-controlled, LEB phase 3 trials in adult and adolescents (12-<18 years) with moderate-to-severe AD. LEB 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 to LEB 250 mg Q2W, LEB 250 mg every 4 weeks (Q4W), or placebo for 36 additional weeks. Clinically meaningful responses were defined as Pruritus-NRS ≤4 (in patients with baseline Pruritus-NRS>4) and DLQI ≤5 (patients with baseline DLQI >5). Proportions of responders at W16 achieving Pruritus-NRS ≤4 and DLQI ≤5 were assessed at W52 (NRI/MI). Results: The proportions of patients reporting Pruritus-NRS ≤4 at W52 were 80.0%/80.4%/73.3% (LEB Q2W/LEB Q4W/placebo arms, respectively). The proportions of patients reporting a DLQI ≤5 response at W52 were 69.6%/74.3%/57.5% (LEB Q2W/LEB Q4W/placebo). Conclusion: At W52, 8 out of 10 W16 LEB responders treated with LEB Q2W or Q4W had mild pruritus (Pruritus-NRS ≤4) and 7 out of 10 had no or minimal effect on patient’s QoL (DLQI ≤5). Thus, continued treatment with LEB in W16 responders provides sustained clinically meaningful improvements in the long-term in both symptoms and QoL in patients with moderate-to-severe AD.
P34
Title:
Efficacy
and Safety of Nalmefene for Opioid-Induced Pruritus (OIP): A
Systematic Review and Meta-Analysis
Submitting
author:
Shah, Bikash Kumar - Maharajgunj Medical campus, MMBS,
Nepal
Additional
Authors:
Bikash Kumar Shah(1), Adesh Kantha(1), Aakash Deo(1)
Maharajgunj Medical Campus, Institute of Medicine, Tribhuvan
University Teaching Hospital(1)
Abstract:
Introduction: Pruritus is a significant side effect of neuraxial opioids, complicating 30–80% of opioid-based analgesia, which reduces patient satisfaction and increases rescue medication use. Nalmefene, a partial κ-opioid receptor agonist and μ-opioid antagonist, is commonly used to relieve opioid overdose, but has inconsistent results in OIP prevention and needs systematic evaluation. Objectives: To quantify nalmefene’s efficacy in OIP prevention/treatment and assess safety across dosing strategies. Methods: Conforming to PRISMA guidelines, a systematic review encompassing MEDLINE, Embase, Cochrane Central, and Scopus employing targeted search strategies was conducted, selecting 10 studies (7 RCTs, 3 observational; n = 1,551). Primary outcomes included pruritus incidence (prophylaxis) and complete relief rate (treatment). Safety outcomes included vomiting and withdrawal reactions. Results: Prophylactic IV nalmefene (0.25–0.5 µg/kg) reduced OIP incidence by 48% (RR 0.52, 95% CI 0.41–0.66) with complete relief of pruritus by 33% (RR 1.33, 1.18–1.50) in the treatment of OIP. Low-dose IV use (OR 0.78) reduced the vomiting episodes, withdrawal reactions increased with oral forms (OR 6.50), and there was no respiratory depression or analgesia reversal. Higher IV doses (>1 µg/kg) increased adverse effects, with no further efficacy. Conclusion: Low dose IV nalmefene (0.25–0.5 µg/kg) is highly effective for OIP prophylaxis and treatment. It demonstrates a favorable safety profile with reduced vomiting risk. Oral formulations should be avoided due to withdrawal reactions. Integration into perioperative protocols can optimize opioid analgesia tolerance.
P35
Title:
Comparative
efficacy of different concentrations of topical tazarotene and
topical tretinoin in acne vulgaris.
Submitting
author:
Sharma, Sunidhi - department of dermatology, government
medical college and hospital, sector 32, chandigarh
Additional
Authors:
MBBS, MD Dermatology
Abstract:
OBJECTIVE: To compare the clinical efficacy of topical 0.025% and 0.05% tretinoin with topical 0.05% and 0.1% tazarotene in acne vulgaris. DESIGN: Randomized Prospective Trial SETTING: It is a single center study conducted in a tertiary level hospital for a duration of 8 weeks. PARTICIPANTS: Patient having acne vulgaris (Grade 1 and 2) of age 18 to 50 years were included in the study. Those who were pregnant and lactating, had any systemic illness and signs and symptoms of hyperandrogenism were excluded from the study. INTERVENTION: 108 patients having mild to moderate facial acne vulgaris were selected and divided equally into 4 groups. Daily application of different concentrations of topical tretinoin and topical tazarotene once at bedtime was advised. Patients were followed at 2 weekly intervals up to 8 weeks and response was graded as per Indian Acne Alliance system. Any adverse events were also noted. MAIN OUTCOME: To compare the clinical efficacy of topical 0.025% and 0.05% tretinoin with 0.05% and 0.1% tazarotene in acne vulgaris. RESULT: The mean improvement in total lesion scores was highest for 0.1% tazarotene at 95.4%. This was followed by 0.05% tazarotene at 91.7%, tretinoin 0.05% at 89.4%, and 0.025% tazarotene at 71.5% at 8 weeks. CONCLUSION: Tazarotene group was associated with a significantly greater treatment success than tretinoin group. All the agents were well tolerated and most of the adverse effects were local and transient. Erythema, burning and peeling were seen more commonly with higher concentrations.
P36
Title:
Oral
Ketotifen and Methotrexate help to achieve long-term relief from
itching in prurigo nodularis
Submitting
author:
Sharma, Ashimav - DERMA CARE Clinic, Bongaigaon, Assam,
India(PIN:783380)
Abstract:
Introduction: Prurigo Nodularis (PN) is a chronic, relapsing dermatological disorder known for its persistent itching and treatment resistance. In clinical practice, there is a continuous need for therapies that are both effective and safe, offering sustained relief and prolonged remission. Objectives: To evaluate the efficacy of oral Ketotifen and weekly low-dose Methotrexate in alleviating itching in patients with Prurigo Nodularis. Methods: This study involved 27 adult PN patients( Male:21;Female:6) with a history of atopy and elevated IgE levels, attending a dermatology clinic. Patients with infected lesions received antibiotics prior to trial initiation. The study group was treated with topical steroids, oral Ketotifen (1–2 mg/day), and Methotrexate (5 mg/week) for 8 weeks. The control group received topical steroids and oral Hydroxyzine 25 mg on an as-needed basis. Both groups were observed for an additional 4 months post-treatment. Results: In the study group, 9 patients reported complete itch relief by the first week, sustained throughout the 8-week treatment. Another 5 patients experienced similar relief by week two. During follow-up, 11 patients remained itch-free, while 3 had minor relapses of itching. In contrast, the control group showed only mild to moderate improvement of itching by the end of the first week, with no further progress. Itching returned promptly after treatment cessation. Conclusions: Combined therapy with oral Ketotifen and low-dose weekly Methotrexate proves effective in controlling itching and maintaining long-term remission in patients with Prurigo Nodularis.
P37
Title:
Therapeutic
impact of low-nickel diet and oral iron in chronic anal itching due
to nickel allergy
Submitting
author:
Sharma, Ashimav - DERMA CARE Clinic, Bongaigaon, Assam,
India(PIN:783380)
Abstract:
Introduction: Pruritus ani (PA) is characterized by chronic itching of the anal and perianal skin, affecting approximately 1–5% of the population. While it is termed idiopathic when no underlying cause is identified, 75% of cases are associated with coexisting pathology. Nickel sensitivity, particularly from dietary sources, is a recognized but often overlooked etiology. Managing PA due to dietary nickel exposure remains a therapeutic challenge. Objectives: To evaluate the efficacy of combining oral iron supplementation with a low-nickel diet (LND) in managing PA associated with nickel allergy in adult women. Methods: Four adult female patients (ages 18–41) with chronic anal itching and confirmed nickel allergy (confirmed through both patch testing and oral nickel sulfate provocation test) were enrolled. Each was prescribed an LND along with oral iron in a dose of 20 mg of elemental iron/day (10 mg just before lunch and 10 mg just before dinner) for 12 weeks. Antihistamines and topical corticosteroids were permitted only on an as-needed basis (SOS). Weekly clinical assessments were performed. Results: All patients experienced reduction in the severity of anal itching within the first week. Three participants achieved complete symptom resolution by week three, and the fourth by week four. None required continued use of antihistamines thereafter, and all remained symptom-free throughout the 12-week period. Conclusions: A low-nickel diet combined with oral iron supplementation appears to be an effective therapeutic strategy for managing PA in patients with confirmed nickel allergy, leading to rapid and sustained symptom resolution.
P38
Title:
Digital
monitoring of sleep efficacy and nocturnal scratch patterns in AD
patients
Submitting
author:
Simmler, Patrik - AbbVie AG, Alte Steinhauserstrasse 14,
Cham, Switzerland
Abstract:
Patrik Simmler, AbbVie, Cham, Switzerland Ieva Saulite, KSSG, Dermatologie, St. Gallen, Switzerland Background: Atopic dermatitis (AD) is a chronic systemic inflammatory disease marked by intense itching, leading to significant sleep disturbances. Traditional objective efficacy endpoints like EASI and IGA do not fully capture the impact of AD on patients’ life quality, whereas parameters including subjective aspects of sleep quality, like SCORAD, do not objectively quantify the latter. This pilot study demonstrates the use of an advanced acousto-mechanic (ADAM) sensor to objectively measure sleep and nocturnal scratching as a novel efficacy parameter in clinical trials. Objective: To evaluate the utility of sensor-based scratch and sleep measurements in assessing the effectiveness of AD treatments and to assess nocturnal scratching behavior in response to upadacitinib, a drug with antipruritic properties. Methods & Results: The study included 10 patients with severe AD tracked for 1 to 4 weeks using an ADAM sensor to record nocturnal scratching and sleep quality. Our analysis revealed that wake after sleep onset (WASO) and sleep efficiency significantly correlate with total scratch time (R=0.53 and 0.49) and number of scratch events (R=-0.47 and -0.39), indicating that the sensor can quantify sleep quality parameters impacted by scratching pattern. Initiation of upadacitinib treatment decreased nocturnal scratch time in 3 of 4 AD patients, increased sleep efficiency in 3 of 4 patients and decreased WASO in 2 of 4 patients as early as week one. Conclusion: Digital scratch sensors offer a promising new dimension for evaluating therapeutic effectiveness in AD clinical trials. By providing objective, quantifiable data on nocturnal scratching, these sensors can complement traditional efficacy measures, offering relevant insights into patient outcomes. The improvement of sleep metrics upon upadacitinib treatment demonstrates the utility of digital measures in future clinical studies for AD and potentially other diseases with itch as a hallmark symptom.
P39
Title:
Tofacitinib
for Prurigo Nodularis: A Promising Off-label Approach via JAK-STAT
Inhibition
Submitting
author:
Singh, Apeksha - calcutta national medical college and
hospital
Abstract:
Despite recent therapeutic advancements, conventional treatments for prurigo nodularis often demonstrate limited efficacy. The clinical application of Janus kinase (JAK) inhibitors in managing this condition remains relatively unexplored. We report a case series of 5 patients of prurigo nodularis successfully treated with the Janus kinase (JAK) inhibitor tofacitinib, with no observed adverse effects. This case series, of successful treatment shows a good efficacy of using JAK inhibitor tofacitinib in the treatment of prurigo nodularis. The positive clinical outcome supports the potential role of cytokine-mediated pathways of the disease. Conclusion-Tofacitinib, a Janus kinase (JAK) inhibitor, may represent a promising therapeutic option for patients with prurigo nodularis, particularly those who are unresponsive to conventional treatments. Keywords: prurigo nodularis, JAK inhibitors, tofacitinib
P40
Title:
Dupilumab
Treatment Corrects Upregulation of Type 2 Inflammatory Cytokines and
Improves Pruritus Symptoms in Patients with Moderate-to-Severe Atopic
Dermatitis
Submitting
author:
Ständer, Sonja - University Hospital Münster, Münster,
Germany
Additional
Authors:
Konstantin Agelopoulos1, Leigh Nattkemper2, Jerry
Bagel3, Inoncent Agueusop4, Mathilde Sautreuil5, Madison Mack6,
Joseph Zahn7, Annie Zhang6, Gil Yosipovitch2 1University Hospital
Münster, Münster, Germany; 2University of Miami, Miami, FL, USA;
3Eczema Treatment Center of New Jersey, East Windsor, NJ, USA;
4Sanofi, Frankfurt, Germany; 5EFOR US, Cambridge, MA, USA; 6Sanofi,
Cambridge, MA, USA; 7Regeneron Pharmaceuticals Inc., Tarrytown, NY,
USA
Abstract:
Chronic pruritus, characteristic of atopic dermatitis (AD), is driven by upregulation of skin expression of type 2 pro-inflammatory cytokines and transient receptor potential ankyrin 1 (TRPA1) expression, a sensory ion channel involved in histamine-independent chronic itch signaling. Objectives: To report the effect of dupilumab on pruritus and key pruritus-related type 2 cytokines by quantifying interleukin (IL)-4, IL-31, and TRPA1 gene expression levels in skin and assessing pruritus. Method: DIFFERENSTAD (NCT04823130) was an open-label, exploratory study. Patients aged ≥18 years with moderate-to-severe AD, pruritus lasting >6 weeks, and Worst Itch Numeric Rating Scale (NRS) score ≥4 received dupilumab 300mg every 2 weeks for 16 weeks. Skin biopsies were obtained from patients’ lesional skin at baseline and post-lesional skin (Week 16, end of treatment [EoT]) and from matched healthy controls. IL-4, IL-31, and TRPA1 gene expression levels in skin were quantified using real-time polymerase chain reaction. Pruritus was assessed using Peak Pruritus NRS (PP-NRS). Results: Patients with AD (n=31) had significantly higher upregulation of IL-4 (P<0.01), IL-31, and TRPA1 (both P<0.0001) at baseline vs healthy controls (n=10). IL-4 (P<0.01), IL-31 (P<0.001), and TRPA1 (P<0.05) levels in patients with AD decreased significantly from baseline to EoT, similar to levels in healthy controls. Mean (SD) PP-NRS score (range 0–10) was 8.47 (1.307) at baseline and 3.05 (2.038) at EoT for patients with AD (P<0.0001). Reductions in PP-NRS correlated with reductions in IL-4 (R=0.59; P=0.015) and TRPA1 (R=0.49; P=0.014) and showed a trend toward significance with IL-31 (R=0.46; P=0.063). Safety was consistent with the known dupilumab safety profile. Conclusions: Dupilumab significantly decreased expression levels of pruritus-related cytokines and TRPA1 in patients with AD, to levels comparable with those of healthy controls, and improved symptoms. These findings reiterate the pivotal role of type 2 cytokines, including IL-4 signaling, in sustaining pruritus pathogenesis in AD.
P43
Title:
Visualization
and Molecular-Pharmacological Analysis of AI-Derived Digital
Biomarkers for Itch
Submitting
author:
Utsumi, Jun - Juntendo Itch Research Center (JIRC),
Institute for Environmental and Gender-Specific Medicine, Juntendo
University Graduate School of Medicine, Chiba, Japan.
Additional
Authors:
Mitsutoshi Tominaga/Juntendo Itch Research Center
(JIRC), Institute for Environmental and Gender-Specific Medicine,
Juntendo University Graduate School of Medicine, Chiba, Japan. Koichi
Miyakawa/Department of Psychiatry, Juntendo University Urayasu
Hospital, Chiba, Japan. Shusuke Yoshimoto/PGV Inc, Tokyo, Japan Liu
Yizhi/PGV Inc, Tokyo, Japan Hideki Matsubara/PGV Inc, Tokyo, 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.
Abstract:
Since the sensation of itch is subjective, and self-assessment by children, the elderly, and individuals with cognitive or communication impairments is often unreliable, an objective measure is needed. In this study, we developed an ultra-sensitive, wearable electroencephalography (EEG) device to quantify itch and tested it in mice. Biopotentials were recorded following administration of the pruritogen chloroquine (CQ) or the antipruritic κ-opioid agonist nalfurafine (NFN). The resulting itch-related profiles were visualized using machine learning analysis. In parallel, we exposed normal human epidermal keratinocytes to the same compounds, performed microarray-based transcriptome profiling, and used the machine learning algorithm t-SNE to visualize gene expression patterns and identify itch-related pathways. CQ increased γ-band power (40–45 Hz), a frequency associated with sensory excitation, suggesting this signal may serve as a digital biomarker of itch. In contrast, NFN produced a β-band signal (approx. 15 Hz), which is associated with anxiolysis and mild arousal. Pretreatment with NFN suppressed the CQ-induced γ-band activity, consistent with its antipruritic effect. Transcriptome analysis showed that both compounds upregulated genes involved in chemical synaptic transmission, though their expression patterns differed. CQ increased the expression of itch-related genes, including ADORA2A, AVPR1A, ASIC1, ASIC3, KIT, TLR2, and TNF. These effects were reduced in the presence of NFN. Together, the in vivo EEG data and in vitro transcriptome findings suggest that γ-band EEG activity measured by a wearable device may serve as an objective digital biomarker for itch. This platform provides a tool for investigating itch mechanisms and advancing the development of antipruritic therapies.
P44
Title:
Effectiveness
of Tildrakizumab in the Treatment of Genital Psoriasis Symptoms in
Austria, Switzerland, and the Czech Republic (CZATCH-Genital-PsO):
28-week interim results
Submitting
author:
Weger, Wolfgang - Department of Dermatology and
Venereology, Medical University of Graz, Graz, Austria
Abstract:
Wolfgang Weger 1, Julia-Tatjana Maul2,3, Spyros Gkalpakiotis4 1Department of Dermatology and Venereology, Medical University of Graz, Austria. 2 Department of Dermatology, University Hospital Zürich, Switzerland 3 Faculty of Medicine, University of Zürich, Switzerland 4 Department of Dermatovenereology, Third faculty of medicine, Charles university and University hospital Kralovske Vinohrady of Prague, Czech Republic Genital psoriasis affects up to 63% of psoriasis patients at least once in their lifetime and burdensome symptoms like itch tend to impair patients’ psychological well-being, and quality of life more than lesions on other body parts. Tildrakizumab is an interleukin-23p19 inhibitor indicated for the treatment of moderate-to-severe plaque psoriasis with demonstrated long-term efficacy and safety. The objectives of this analysis were to assess the effectiveness of tildrakizumab in the treatment of the genital psoriasis symptoms like itch in clinical routine. CZATCH-Genital-PsO is an ongoing 12-month, non-interventional, observational, multinational study carried out at sites in Austria, Switzerland, and the Czech Republic. Genital Psoriasis Symptom Scale (GPSS) was used to evaluate the impact of 8 genital psoriasis symptoms: itch, pain, discomfort, stinging, burning, redness, scaling, and cracking. Here, we report 28-week interim data based on observed cases. A total of 48 patients were included in the interim analysis (58% male, mean [± SD] age of 44 [± 15] years, mean body mass index of 27.4 [± 5.3] kg/m2, 79% had scalp involvement and 44% nail involvement). Mean Physician’s Global Assessment Score decreased from 3.02 (± 0.54) at baseline to 1.05 (± 0.94) at W28 (p<0.001). The mean total GPSS (0 no severity - 80 worst imaginable severity) decreased from 38.8 ± 20.0 at baseline to 10.2 ± 16.2 at W28. The mean GPSS for worst itch in the past 24 hours (NRS 0-10) decreased from 5.60 ± 2.77 at baseline to 1.91 ± 2.60 at W28 (p<0.001). In a real-world setting, tildrakizumab significantly improved burdensome genital psoriasis symptoms like itch at W28.
P45
Title:
Nemolizumab
long-term efficacy in patient-reported outcomes up to 100 weeks in
the OLYMPIA open-label extension study in patients with prurigo
nodularis: An interim analysis
Submitting
author:
Weisshaar, Elke - Division of Occupational Dermatology,
Department of Dermatology, University Hospital Heidelberg,
Heidelberg, Germany
Additional
Authors:
Shawn Kwatra/University of Maryland School of Medicine,
Baltimore, MD, USA; Maxwell Sauder/ University of Toronto, Toronto,
ON, Canada; Curdin Conrad/ Lausanne University Hospital CHUV
Lausanne, Switzerland; Andrew E. Pink/St. John’s Institute of
Dermatology, Guy’s & St. Thomas’ NHS Foundation Trust London,
UK; Sebastien Barbarot/ University Hospital, Nantes, France; Laurent
Misery/Morvan Hospital, University Hospital of Brest, Brest, France;
Jacek C Szepietowski/ Wroclaw Medical University, Wrocław, Poland;
Serge Boulinguez/ Medical University of Toulouse, Toulouse, France;
Lone Skov/ Copenhagen University Hospital - Herlev and Gentofte,
Copenhagen, Denmark; Athanasios Tsianakas/ Fachklinik Bad Bentheim,
Bad Bentheim, Germany; Aliene Noda/Galderma R&D, Zug,
Switzerland; Xiaoxiao Chen/Galderma Laboratories, Dallas, TX, USA;
Zarif Jabbar-Lopez/Galderma R&D, Zug, Switzerland; Christophe
Piketty/Galderma R&D, Zug, Switzerland; Sonja Ständer/
University Hospital Münster, Münster, Germany
Abstract:
Introduction: Prurigo nodularis (PN), a chronic neuroimmune skin disease, requires long-term treatment. Nemolizumab is the first interleukin-31 receptor alpha antagonist approved for PN in several countries including the USA and the EU. Objective: To report patient-reported outcomes (PROs) of an interim analysis (IA), as of July 21, 2024, of the ongoing open-label long-term extension trial (OLYMPIA-LTE [NCT04204616]). Methods: Adults with moderate-to-severe PN, who completed phase 2a/3 lead-in trials, were eligible for the 184-week OLYMPIA-LTE trial. All patients received open-label nemolizumab monotherapy (30/60 mg Q4W based on body weight [<90 kg/ ≥90 kg]). Efficacy assessments included the proportion of patients achieving the Investigator’s Global Assessment (IGA) score of 0/1 (clear/almost clear), a ≥4-point improvement from the lead-in baseline in weekly average Peak Pruritus Numerical Rating Scale (PPNRS4) and Sleep Disturbance Numerical Rating Scale (SDNRS4), PPNRS<2, and SDNRS<2. The safety was assessed throughout the study. Observed cases of overall population, regardless of rescue medication usage, are presented. Results: Of 508 patients, 290 (57%) completed week (W) 100 (median exposure: 839.5 days) and 147 (29%) discontinued the study by this IA. At W100, 74% of evaluable patients achieved IGA score of 0/1, 92% achieved PPNRS4, 74% achieved PPNRS<2, 86% achieved SDNRS4, and 80% achieved SDNRS<2. The mean (SD) PPNRS was 1.3 (2.0), SDNRS 0.9 (1.8), and DLQI 3.1 (4.7) at W100. The most frequent adverse events were infections (e.g., coronavirus disease-2019, nasopharyngitis, and upper respiratory tract infection). Conclusion: In this IA, long-term efficacy was demonstrated in patients with PN treated with nemolizumab open-label for up to 100 weeks, with PROs indicating clinically meaningful and sustained improvements in itch, sleep disturbance, and quality of life at W100 among those with evaluable data. The long-term safety profile of nemolizumab was consistent with previous findings, with decreased/similar AE and SAE rates over time.
P46
Title:
Aquagenic
Pruritus Questionnaire – Predicting Myeloproliferative Neoplasms in
Patients with Aquagenic Pruritus
Submitting
author:
Witte, Felix - 1Department of Dermatology, Section
Pruritus Medicine and Center for chronic pruritus, University
Hospital Münster, Münster, Germany
Additional
Authors:
Elke Weisshaar2, Martin Metz3, Steffen Koschmieder4,
Susanne Isfort4,5, Andreas E Kremer6, Martin Griesshammer7, Svenja
Royeck1, Sonja Ständer1, Claudia Zeidler1 2Department of
Dermatology, Division of Occupational Dermatology, University
Hospital Heidelberg, Heidelberg, Germany; 3Institute of Allergology,
Charité - Universitätsmedizin Berlin, Berlin, Germany; 4Department
of Hematology, Oncology, Hemostaseology and Stem Cell
Transplantation, Medical Faculty, RWTH Aachen University, Aachen,
Germany; 5Department of Hematology, Hemostasis, Oncology and Stem
Cell Transplantation, Comprehensive Cancer Center Lower Saxony,
Hannover Medical School, Hannover, Germany; 6Department of
Gastroenterology and Hepatology, University Hospital Zürich,
University of Zürich, Zürich, Switzerland; 7University Clinic for
Hematology, Oncology, Hemostaseology and Palliative Care, Johannes
Wesling Medical Center Minden, University of Bochum, Minden, Germany
Abstract:
Introduction Aquagenic pruritus (AP) is an underrecognized condition in which patients perceive itch following contact with water on clinically non lesional skin. AP is frequent in patients suffering from myeloproliferative neoplasms (MPN) such as polycythemia vera and may manifest several years prior to the clinically visible diagnosis of MPN. Objectives To date, there is no validated patient reported outcome measure (PROM) assessing AP and its potential association with MPN. Methods In this multi-phase study, a portfolio of 8 questions relevant to AP was developed and validated in a cohort of 77 patients with AP and 50 patients with chronic, non-aquagenic pruritus (CP). These questions were consequently reduced to those relevant for AP to distinguish between patients with and without a diagnosed MPN, resulting in the novel AP questionnaire (APQ). The APQ was validated in a cohort of 76 AP patients, 37 (49%) of whom suffered from an MPN, and 76 CP patients without AP. Finally, the predictive power of the APQ was retrospectively tested in the first cohort. Results Four questions were identified as central to differentiating AP patients with and without MPN, resulting in the new APQ. The questions were validated successfully. Sensitivity and specificity of the APQ reached 97.3% and 79.5%, respectively. The new APQ classified 5 patients as AP patients with MPN who were diagnosed with MPN at a later stage. Conclusions APQ is the first validated PROM for patients suffering from AP, detecting a potential relationship to MPN with high sensitivity. APQ is a useful addition to the standard of care in patients suffering from AP, potentially shortening the delay of MPN diagnosis.
P47
Title:
Patient
reported outcomes and symptom improvements across subtypes of Chronic
Hand Eczema: outcomes from the Phase 3 DELTA-1 and DELTA-2 trials
Submitting
author:
Worm, Margitta - Division of Allergy and Immunology,
Department of Dermatology, Venerology and Allergy,
Charité-Universitätsmedizin Berlin, Berlin, Germany;
Additional
Authors:
Robert Bissonnette [1], Timo Buhl [2], Parbeer Grewal
[3,4], Emma Guttman-Yassky [5], Ziad Reguiaï [6], Eric L. Simpson
[7], Margitta Worm [8], Douglas Maslin [9,10], Jenny M. Norlin [9],
Henrik Thoning [9], Raj Chovatiya [11,12]; [1] Innovaderm, Montreal,
Canada; [2] Univ. Göttingen, Germany; [3] Univ. Alberta, Canada; [4]
Rejuvenation Derm., Canada; [5] Mount Sinai, NY, USA; [6]
Polyclinique Courlancy, France; [7] Oregon Health Sci. Univ.,
Portland, USA; [8] Charité - Univ. Med. Berlin, Germany; [9] LEO
Pharma A/S, Denmark; [10] Addenbrooke's Hosp., UK; [11] Rosalind
Franklin Univ., USA; [12] Cent. Med. Derm. + Immunol. Res., Chicago,
USA.
Abstract:
Introduction: In parent DELTA 1 and 2 trials, a topical pan-JAK inhibitor, demonstrated efficacy vs. cream vehicle in adults with major etiological (irritant contact/allergic contact/atopic dermatitis [ICD/ACD/AD]) and morphological (hyperkeratotic/vesicular) subtypes of moderate to severe Chronic Hand Eczema (CHE). Objectives: Post hoc analysis of the DELTA 1/2 trials to quantify improvements in patient-reported outcomes (PROs) and assess the time to achieve clinically meaningful improvement with delgocitinib cream vs. cream vehicle in adults with moderate to severe CHE across CHE subtypes. Methods: PROs, including Hand Eczema Symptom Diary (HESD) itch, HESD pain, Dermatology Life Quality Index (DLQI), and Hand Eczema Impact Scale (HEIS), were assessed in pooled DELTA 1/2 patients treated with twice daily delgocitinib cream (N=639) or cream vehicle (N=321) through Week (W) 16. Results: Responder rates for ≥4-point improvement in HESD itch, HESD pain, and DLQI at W16 were greater with delgocitinib cream than cream vehicle across all CHE subtypes. In vesicular CHE, 53.0%, 57.0%, and 72.9% of patients treated with delgocitinib cream achieved clinically meaningful improvements vs. 21.6%, 28.1%, and 47.1% with cream vehicle, respectively. Significantly greater response was achieved with delgocitinib cream vs. cream vehicle (P<0.05) within 4 weeks for all CHE subtypes, and as early W1 for DLQI (for ICD/AD/vesicular). Similar response time was observed for HEIS, with clinically meaningful responses from W2. Greater improvements from baseline in absolute HESD itch and HESD pain were seen with delgocitinib cream versus cream vehicle (P<0.05) for all subtypes by Day 10, and as early as Day 1. Conclusions: Delgocitinib cream demonstrated clinically meaningful improvements at W16 in itch, pain, and quality of life in adults across all major subtypes of moderate to severe CHE. These improvements were statistically significant with delgocitinib cream vs. cream vehicle as early as W1, demonstrating the rapid efficacy of delgocitinib across CHE subtypes.
P48
Title:
Successful
Treatment of Skin-Picking (Excoriation) Disorder with Upadacitinib: A
Case Report
Submitting
author:
Xie, Zhiqiang - Department of Dermatology, Third
Hospital of Peking University, Beijing 100191, China
Abstract:
Introduction: Skin picking disorder (SPD), also referred to excoriation disorder, is a disabling behavioral disorder characterized by compulsive and repetitive picking of the skin. The treatment of SPD is challenging and requires a multidisciplinary approach.
Objectives: Exploring the treatment of SPD with anti-inflammatory and antipruritic small molecule drugs.
Methods: A 12-year-old female patient developed conscious or unconscious skin-picking behaviors due to emotional stress 6 years ago, often causing skin excoriation and bleeding. Dermatological examination revealed epidermal excoriation, linear scratch marks, and blood crusts on both sides of the face, neck, back, and extremities, most prominently on the lower limbs, with areas of old scars and hyperpigmentation. The diagnosis was skin-picking disorder with comorbid anxiety. we report the case of a 12-year-old female patient with severe skin-picking disorder who responded to treatment with oral Upadacitinib (15 mg/day).
Results: Treatment with oral Upadacitinib (15 mg/day) was initiated. After 4 weeks of treatment: The pruritus NRS score decreased from 3 to 0, Skin Picking Scale-Revised (SPS-R) score reduced from 15 to 5, and EASI score improved from 10.6 to 1.6. After 8 weeks of treatment: Pruritus NRS remained at 0, SPS-R score decreased to 3, EASI score dropped to 0.4, indicating basic clinical cure.
Conclusion: A patient with SPD was treated successfully with Upadacitinib, a Janus kinase (JAK) inhibitor is presented.
P49
Title:
Lebrikizumab
monotherapy maintained improvement of itch and sleep-loss due to itch
after two years in patients with moderate-to-severe atopic dermatitis
Submitting
author:
Yosipovitch, Gil - Itch Center, Dr Phillip Frost
Department of Dermatology and Cutaneous Surgery, University of Miami
Hospital, Miami, Florida, USA
Additional
Authors:
Gil Yosipovitch 1 (Presenting author), Peter A. Lio 2,
David Rosmarin 3, Marta Casillas 4, Fan Emily Yang 4, Chaoran Hu 4,
Evangeline Pierce 4, Laia Bardolet Boncompte 5, Franz J. Legat 6,
Jose-Manuel Carrascosa 7, Sonja Ständer 8. 1 Itch Center, Dr Phillip
Frost Department of Dermatology and Cutaneous Surgery, University of
Miami Hospital, Miami, Florida, USA; 2 Northwestern University
Feinberg School of Medicine; Medical Dermatology Associates of
Chicago, Chicago, Illinois, USA; 3 Indiana University School of
Medicine, Indiana, USA; 4 Eli Lilly and Company, Indianapolis,
Indiana, USA; 5 Almirall, Barcelona, Spain; 6 Department of
Dermatology, Medical University of Graz, Graz, Austria; 7 Dermatology
Department, Hospital Universitari Germans Trias i Pujol, UAB, IGTP,
Badalona, Spain; 8 Department of Dermatology and Center for Chronic
Pruritus (KCP), University Hospital Münster, Münster, Germany.
Abstract:
Introduction: Atopic dermatitis (AD) is a chronic disease with itch and sleep-loss due to itch as key symptoms, which requires long-term treatment and sustained response. Objectives: To describe the impact of lebrikizumab on itch and sleep-loss due to itch at 104-weeks in a long-term extension study, ADjoin (NCT04392154). Methods: Responders from monotherapy ADvocate1&2 (achieved Eczema Area and Severity Index 75 or Investigator Global Assessment score (0,1), without rescue medication), who completed ADvocate1&2 and enrolled into ADjoin, received lebrikizumab 250 mg every 2-weeks (Q2W) or 4-weeks (Q4W) for an additional 52-weeks. Itch was assessed using Pruritus Numeric Rating Scale (NRS), an 11-point scale [0 (no itch) to 10 (worst imaginable itch)]. Sleep-loss due to itch was assessed using Sleep-Loss Scale (SLS), a 5-point Likert scale [0 (not at all) to 4 (unable to sleep at all)]. Outcomes are reported as observed at Week 104: change from baseline (CFB), Pruritus NRS (0,1), ≥3-point improvement in Pruritus NRS, ≥1-point and ≥2- point improvement in SLS. ADvocate1&2 data were pooled. Results: At Week 104, CFB in Pruritus NRS was -5.24 Q2W and -5.06 Q4W, Pruritus NRS (0,1) was 57.4% Q2W and 55.4% Q4W, and ≥3-point improvement in Pruritus NRS was 85.2% Q2W and 85.5% Q4W. At Week 104, CFB in SLS was -1.78 Q2W and -1.52 Q4W, ≥1-point improvement in SLS was 93.0% Q2W and 94.0% Q4W and ≥2-point improvement in SLS was 64.3% Q2W and 71.4% Q4W. Conclusion: Patients with moderate-to-severe AD achieved and maintained improvement of itch and sleep-loss due to itch after two-years of treatment with lebrikizumab monotherapy.
P50
Title:
Trial in
Progress: A Phase 2, Randomized, Double-Blind, Placebo-Controlled
Study to Assess the Efficacy and Safety of Barzolvolimab in Patients
with Moderate to Severe Atopic Dermatitis
Submitting
author:
Yosipovitch, Gil - University of Miami Miller School of
Medicine, Dr. Phillip Frost Department of Dermatology and Cutaneous
Surgery, 5555 Ponce de Leon, Coral Gables, Miami, FL, USA
Abstract:
Background: Barzolvolimab is a monoclonal antibody that binds to the receptor tyrosine kinase KIT, thereby inhibiting its activation by stem cell factor (SCF). KIT is expressed on multiple cell types, including mast cells (MCs), where it regulates degranulation, differentiation, proliferation, survival, and chemotaxis. Emerging science supports the role of MCs in the pathogenesis of atopic dermatitis (AD) by contributing to epithelial barrier dysfunction, immune cell recruitment, and neuroinflammation. KIT inhibition leading to MC depletion is a potential therapeutic approach in AD. In a Phase 1b study, 23 participants with prurigo nodularis (PN) received a single intravenous dose of barzolvolimab or placebo. At Week 8, barzolvolimab 3.0 mg/kg led to a 46.1% mean reduction in the Worst Itch Numeric Rating Scale (WI-NRS), with 57.1% achieving a ≥4-point reduction, compared to 29.7% and 25.0%, respectively, in the placebo group. Investigator Global Assessment (IGA) scores of 0/1 were reported in 29% of barzolvolimab-treated participants and 0% with placebo. Barzolvolimab has also demonstrated clinical efficacy in chronic spontaneous urticaria (CSU). In a randomized, double-blind, placebo-controlled Phase 2 trial involving 207 participants with moderate to severe CSU, subcutaneous barzolvolimab significantly reduced Urticaria Activity Score over 7 days (UAS7) at Week 12. Least squares mean changes from baseline were –23.02 (150 mg Q4W) and –23.87 (300 mg Q8W), versus –10.47 with placebo (P < 0.0001 for both comparisons). Methods: This Phase 2 trial evaluates the efficacy and safety of two barzolvolimab regimens (150 mg or 300 mg Q4W for 16 weeks following 450 mg loading doses) in adults with moderate to severe AD. Participants must have an Eczema Area and Severity Index, (EASI) ≥16, IGA ≥3, and inadequate response to topical corticosteroids, topical calcineurin inhibitors, and biologics. The trial is actively recruiting.
P52
Title:
Correlation
of Serum Biomarkers with Disease Severity in Chronic Spontaneous
Urticaria: An Observational Study
Submitting
author:
Ahmed, SK Shahriar - Wizderm Speciality Skin and Hair
Clinic
Abstract:
Introduction: Chronic-Spontaneous-Urticaria (CSU) is a disease with distinct type I and type IIb endotypes, contributing to variable disease presentations and management challenges. Although several biomarkers have been studied for their correlation with CSU severity, consistent associations remain unclear. Objectives: To assess the correlation between specific biomarkers and CSU severity. Methods: This was an observational cross-sectional study that included a total of 30 patients with CSU who were categorized into three-groups based on UAS7 scores: mild (n=8), moderate (n=16), and severe (n=6). The following biomarkers were assessed: Absolute-Basophil-Count (ABC), C-reactive-Protein (CRP), D-dimer, Mean-Platelet-Volume (MPV), Vitamin-D3, Absolute-Eosinophil-Count (AEC), Immunoglobulin E(IgE), and Anti-Thyroid-Peroxidase-Antibody (Anti-TPO-Ab). Data were analyzed using ANOVA and Kruskal-Wallis tests, and Pearson-correlation-coefficients were calculated. Results: The mean ABC was found to be 64.75 in the mild-group, 63.88 in the moderate-group, and 86.33 in the severe-group, (p = 0.719). The mean AEC was 14.19 cells/µL,15.41 cells/µL, and 17.50 cells/µL respectively (p = 0.7828). The mean CRP levels were 3.88 mg/L, 5.50 mg/L, and 4.26 mg/L respectively (p = 0.690). Mean D-dimer levels were fairly consistent across all groups—0.5212 µg/mL, 0.5013 µg/mL, and 0.5033 µg/mL respectively (p=0.992). The MPV showed minimal variation, recorded as 9.34 fL, 10.19 fL, and 9.22 fL (p = 0.581). Mean Vitamin-D3 levels were higher in the mild group (25.85 ng/mL) compared to moderate (20.39 ng/mL) and severe (21.52 ng/mL) groups. Interestingly, serum mean IgE levels showed a significant rising trend with disease severity—8.88 IU/mL, 16.87 IU/mL, and 20.67 IU/mL respectively (p = 0.0304). Lastly, anti-TPO-Ab levels were found to be 18.81 IU/mL, 15.44 IU/mL, and 11.25 IU/mL respectively (p = 0.2817). Conclusion: Among all evaluated biomarkers, only serum IgE showed a statistically significant correlation with CSU severity. Other did not demonstrate significant associations.
P53
Title:
Inhibition
of IL-13 pathways in healthy volunteers demonstrates significant
analgesic effect on experimentally provoked pressure and heat pain.
Submitting
author:
Arendt-Nielsen, Lars - Center for Neuroplasticity and
Pain, School of Medicine, Aalborg University and Aalborg University
Hospital, Aalborg, Denmark
Additional
Authors:
B.A. Markussen1,2, S. Lo Vecchio1, G.E. Aliotta1, J.
Elberling3,4 1Department of Health Science and Technology, School of
Medicine, Aalborg University, Aalborg, Denmark 2Department of
Gastroenterology & Hepatology, Mech-Sense, Clinical Institute,
Aalborg University Hospital, Aalborg, Denmark 3Department of
Dermatology and Allergy, Herlev and Gentofte Hospital, Herlev,
Denmark 4Department of Clinical Medicine, University of Copenhagen,
Copenhagen, Denmark
Abstract:
Animal data suggest that IL-13 does not directly trigger acute itch or pain but may cause increased neuronal sensitivity to pruritogens and in specific pain conditions. The interaction between itch and pain pathways are not fully understood in neither animals nor humans but IL-13 may be one common denominator. With the development of monoclonal antibodies targeting specifically IL-13 (Lebrikizumab), it’s now possible to directly investigate the role of IL-13 signaling in human sensory processing, and particularly the role in pain processing. Aim: To evaluate the analgesic effect of IL-13 modulation by Lebrikizumab on experimentally provoked pain. Methods: Reference areas on the forearm of 10 healthy participants were selected for pain assessments at baseline, week 2, 4 and 6. During each session pain was experimentally provoked using Mechanical pinprick Pain Threshold (MPT), Pressure Pain Threshold (PPT), Cold Pain Threshold (CPT), Heat Pain Threshold (HPT), and pain ratings (0 to 10) to Supra-Threshold Heat Stimuli (STHS). Participants received a subcutaneous injection of 500 mg Lebrikizumab at baseline and week 2 and 250 mg at week 4. Results: By week 4 (557 ± 189kPa, p =0.001) and week 6 (691 ± 276kPa, p<0.001) the PPT increased significantly from baseline (392 ± 109kPa). At week 2 (43.7 ± 3.1oC, p=0.021), week 4 (43.6 ± 3.3 oC, p=0.023), and week 6 (44.7 ± 2.8 oC, p<0.001) the HPT increased significantly compared with baseline (42.2 ± 3.4 oC) STHS pain ratings decreased significantly in every session (week 2: 6.7 ± 1.8, p = 0.038; week 4: 6.1 ± 2.3, p<0.001; week 6: 6.2 ± 2.4, p<0.001) compared with baseline (7.3 ± 1.5). CPT and MPT showed no significant differences between sessions. Conclusions: Lebrikizumab modulates the IL-13 related pain pathways and caused significant analgesia to pressure and heat provoked pain.
P54
Title:
Dioxin
Exposure and Skin Sensory Dysfunction: Insights from Yusho Patient
Analysis
Submitting
author:
Ashida, Miwa - 1 Department
of Dermatology, Nagasaki University Graduate School of Biomedical
Sciences, 1-7-1, Sakamoto, Nagasaki 852-8501, Japan 2 Research
and Clinical Center for Yusho and Dioxin, Kyushu University Hospital,
3-1-1, Maidashi, Higashi-ku, Fukuoka 812-8
Abstract:
Miwa Ashida1,2, Naoya Murayama1, Yoshiyuki Kamio1, Mariko Yozaki1, Yutaka Kuwatsuka1, Takeshi Nakahara2, Hiroyuki Murota1 Introduction: The activation of the aryl hydrocarbon receptor (AHR) due to dioxin exposure leads to skin barrier dysfunction and immune dysregulation, thereby exacerbating dermatitis and chronic pruritus. Fifty-seven years following a mass food poisoning incident in western Japan (Yusho), caused by dioxin-contaminated cooking oil, a significant number of affected individuals continue to exhibit elevated blood dioxin levels and experience persistent subtle sensory abnormalities, including itching, numbness, and paresthesia. Objectives: This study aims to examine the cutaneous sensations experienced by patients with Yusho through physiological assessments, alongside the quantification of neurotrophic factors and neurotransmitters in their blood. Methods: Sensory evaluations for tactile, warm, and cold sensations were conducted utilising von Frey filaments and thermal stimulators (n=16). Furthermore, the concentrations of artemin (n = 31), serotonin (n = 29), norepinephrine (n = 26), and dopamine (n = 26) in the blood were quantified. This study also examined the correlations between these parameters and blood dioxin concentrations, including polychlorinated biphenyls (PCB), polychlorinated quarter phenyls (PCQ), and polychlorinated dibenzofurans (PCDF). Results: While no statistically significant differences were observed between patients and healthy controls, certain patients demonstrated diminished tactile sensitivity and reduced cold sensation. Weak correlations were identified between blood artemin and PCQ concentrations, as well as between dopamine and PCB concentrations. Conclusion: These findings suggest a potential role of dioxins in skin dysesthesia and contribute to a more comprehensive understanding of the pathophysiological mechanisms underlying skin sensory disturbances in patients with Yusho.
P55
Title:
Clinical
profile and diagnostic criteria in brachioradial pruritus and
notalgia paresthetica
Submitting
author:
Brenske, Anna - University Hospital Münster, Department
of Dermatology and Venereology, Von-Esmarch-Straße 58, 48149
Muenster, Germany
Additional
Authors:
Anna Brenske MD1* Alexandra Nina Kramer1* Lea-Sophie
Stahl MD1 Claudia Zeidler PD Dr. med.1 Sonja Ständer Prof. Dr. med.
Dr. h.c.1 Manuel P Pereira MD, PhD2,3 1Department of Dermatology and
Venereology, University Hospital Münster, Germany 2Institute of
Allergology, Charité - Universitätsmedizin Berlin, corporate member
of Freie Universität Berlin and Humboldt-Universität zu Berlin,
Berlin, Germany 3Fraunhofer Institute for Translational Medicine and
Pharmacology (ITMP), Allergology and Immunology, Berlin, Germany
*equally contributed
Abstract:
Introduction Brachioradial pruritus (BRP) and notalgia paresthetica (NP) are chronic pruritic neuropathies marked by persistent itch without primary skin lesions, often leading to secondary changes from scratching. Despite their prevalence, these conditions remain relatively unknown, which may hinder their diagnosis. Objectives This study aimed to define diagnostic criteria for BRP and NP by characterizing their clinical profiles. Methods A retrospective analysis of 1,022 patients with BRP (n=760) or NP (n=262) was conducted at the Center for Chronic Pruritus (KCP), University Hospital Münster. Only patients with fully documented first consultations between 2012 and 2022 were included. Clinical data—itch intensity, sensory symptoms, trigger factors, intraepidermal nerve fiber density (IENFD), and radiologic findings (CT, MRI, X-ray)—were extracted from the ORBIS electronic medical record system. Statistical analysis used independent-samples t-tests and chi-square tests in SPSS v28. Results Mean (±SD) itch intensity scores (past 24 hours) assessed using the numerical rating scale (NRS) were higher in BRP (5.3±2.3) than NP (4.7±2.4; p=0.04); worst itch showed no significant differences (BRP: 5.7±2.3; NP: 5.1±2.5; p=0.075). Radiologic-pathologic correlation with itch localization was significant in BRP but absent in NP (p<0.001). Pruritus localization and sensory quality were significant diagnostic indicators for BRP (p<0.001), while no significant association was found for NP. Trigger factors were not independently diagnostic (p<0.05), except cold application (“ice-pack sign”) which is a clinical indicator for BRP. IENFD in lesional skin was reduced in BRP and thus diagnostically relevant (p<0.001), while in NP, IENFD was not altered in most patients. Conclusion Radiologic correlation and pruritus characteristics are strong diagnostic indicators for BRP, while NP remains diagnostically less distinct and therefore more challenging to diagnose. IENFD measurement is crucial for BRP but with no diagnostic value in NP. These findings enable more precise clinical differentiation, encouraging a multidisciplinary approach to diagnosis and therapy.
P57
Title:
Bile
Acid Conjugation Profiles Differentiate Pruritus Across Hepatic and
Renal Diseases
Submitting
author:
Düll, Miriam - Department of Medicine 1,
Friedrich-Alexander-University Erlangen-Nürnberg, Germany 2
Deutsches Zentrum Immuntherapie DZI, Erlangen, Germany 3 Institute of
Physiology and Pathophysiology, Friedrich-Alexander-University
Erlangen-Nürnberg, Germany
Additional
Authors:
Miriam M. Düll1,2*, Manfred Rauh3, Peter
Dietrich1,2,4, Marcel Vetter1,2, Thomas Mettang5, Andreas E.
Kremer1,2,6 1 Department of Medicine 1, University Hospital Erlangen
and Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen,
Germany 2 Deutsches Zentrum Immuntherapie DZI, Erlangen, Germany 3
Department of Pediatrics and Adolescent Medicine, University Hospital
Erlangen and Frie-drich-Alexander-University Erlangen-Nürnberg,
Erlangen, Germany 4 Institute of Biochemistry, Emil-Fischer-Zentrum,
Friedrich-Alexander-University Erlangen-Nürnberg, Germany 5
Department of Nephrology, DKD Helios Clinic, Wiesbaden, Germany 6
Department of Gastroenterology and Hepatology, University Hospital
Zürich, University of Zürich, Zürich, Switzerland
Abstract:
Introduction: Chronic pruritus occurs in both hepatic and renal diseases but remains poorly understood mechanistically. While total bile acid levels have been widely studied, bile acid conjugation patterns may better reflect pruritogenic activity. Objectives: To investigate whether the glycine-to-taurine (G/T) conjugation ratio of circulating bile acids is associated with pruritus in patients with liver disease and chronic kidney disease–associated pruritus (CKD-aP). Methods: Serum samples from 40 patients with hepatobiliary diseases (20 with pruritus, 20 without) and 20 hemodialysis patients (10 with CKD-aP, 10 without) were analyzed by LC–MS/MS. Quantified bile acids included glycine- and taurine-conjugated cholic and chenodeoxycholic acids. Pruritus was assessed using the Numeric Rating Scale (NRS). Group comparisons used the Mann–Whitney U test. Results: In both the hepatic and CKD cohorts, patients with chronic pruritus had significantly lower G/T ratios than non-pruritic controls (p < 0.05). This reduction was driven primarily by elevated levels of taurine-conjugated bile acids. Notably, similar conjugation patterns were observed across etiologies, suggesting a shared biochemical itch phenotype in systemic pruritus. Conclusion: These findings suggest that bile acid conjugation state—rather than total bile acid levels—may play a central role in the pathogenesis of chronic pruritus in both hepatic and renal disease. The G/T ratio may serve as a mechanistic biomarker of systemic itch and a potential tool for symptom stratification. Ongoing work aims to link these molecular signatures with in vivo sensory testing and treatment response.
P58
Title:
Pruritus
and Sensory Dysfunction in Yusho Patients: Implication of Elevated
Sema3A in Dioxin-Induced Neuropathy
Submitting
author:
Ehara, Daisuke -
Abstract:
Over 50 years ago, a major health crisis known as Yusho occurred in Japan due to the ingestion of rice bran oil contaminated with high levels of dioxins. This condition gained global attention and is characterized by persistent symptoms including pruritus, pain, sensory disturbances, and inflammatory skin lesions. The neurological complications associated with dioxin exposure predominantly involve sensory dysfunction, likely due to peripheral neuropathy, but the underlying mechanisms remain unclear. It is an urgent issue to elucidate the mechanisms underlying sensory disturbances and cutaneous inflammation accompanied by pruritus in Yusho patients. We evaluated tactile, warm, and cold sensation in Yusho patients using Von Frey filaments and thermosensory testing. Additionally, serum levels of Sema3A were measured by ELISA, and Sema3A expression in skin tissue was assessed. Yusho patients tended to show reduced tactile sensitivity compared to controls. Serum levels of Sema3A were significantly elevated in the Yusho group. These findings suggest that dioxin exposure may cause abnormalities in peripheral nerve innervation of the skin, contributing to sensory disturbances such as pruritus.
P59
Title:
Comprehensive
Review of Scabies: Pathogenesis, Diagnosis, and Treatment Strategies
Submitting
author:
Goguadze, Mariami - Mariami Goguadze, Avtandil
Gobejishvili
European University, Tbilisi, Georgia
Abstract:
Introduction:
Characterised by persistent itching and inflammation, scabies results from infestation with Sarcoptes scabiei var. hominis. hominis, known for triggering intense itching and skin irritation. The condition is widespread globally, particularly in settings with inadequate hygiene and overcrowding, and poses significant clinical and social challenges due to its contagious nature.
Objectives:
The primary goal of this review is to provide a thorough understanding of scabies, including the biology of the causative organism, its transmission, host-pathogen interactions, clinical presentation, diagnostic strategies, and treatment methods.
Methods:
This review utilised a qualitative analysis of current peer-reviewed scientific literature. Research was drawn from medical databases and journals specializing in dermatology and infectious diseases. Sources were selected to cover a range of topics including parasite biology, immunological responses, clinical features, diagnostic innovations, and pharmacological as well as non-pharmacological interventions.
Results:
Female scabies mites create burrows in the outer skin layers to lay eggs, initiating an infestation cycle that results in hypersensitivity reactions and pruritic rashes. Diagnostic confirmation involves identifying mites or eggs via microscopic examination or dermatoscopy. Topical permethrin is widely recommended for typical cases, while oral ivermectin is effective for systemic treatment. Inadequate hygiene and immunosuppression are key contributors to severe cases.
Conclusion:
Strengthening early detection systems, improving hygiene education, and ensuring access to care are key components in reducing disease burden and preventing community-wide outbreaks.
P60
Title:
Characteristics
of pruritus in lichen planopilaris and frontal fibrosing alopecia - a
single-center study.
Submitting
author:
Kolcz, Kinga - Department of Dermatology, Institute of
Medical Sciences, Medical College of Rzeszow University, Rzeszow,
Poland
Abstract:
Introduction: Lichen planopilaris (LPP) and frontal fibrosing alopecia (FFA) are the most common causes of lymphocytic scarring alopecia. In addition to hair loss, itching of the scalp is a common accompanying symptom. Objectives: Characteristics of pruritus and other associated subjective symptoms in the course of LPP, FFA or coexistence of LPP and FFA. Methods: Sixty-one patients with scarring alopecia were analyzed (LPP = 16; FFA = 33; coexisting LPP-FFA = 12). Itch severity and characteristics were assessed using a Visual Analogue Scale (VAS), 4-item Itch Questionnaire and 12-item Descriptive Pruritus Assessment Questionnaire. Results: Pruritus of the scalp occurred in 73.8% of patients included in the study. The majority of patients declared daily pruritus, and the itching episodes lasted less than 10 minutes and most often occurred in the evening. The average severity at the time of the study was VAS 2.4±2.4, while the maximum severity was VASmax 5.3 ± 3.1. The severity of pruritus was also divided by disease entity. For FFA, the mean severity at the time of examination was VAS 2.0±2.5, for LPP VAS 2.8±2.6 and in the case of coexistence of FFA and LPP 2.8 ± 2.2. While the maximum severity during the course of the disease was 4.6±3.2, 6.2±2.6 and 5.9±3.3, respectively. Pruritus was most frequently accompanied by tingling (19.7%) or burning (14.8%) sensations. Factors that most often aggravate itching were sweating, heat, stress and hot water. In contrast, cold water and cold air often relieved symptoms. Conclusion: Pruritus was the main subjective complaint reported by patients suffering from LPP, FFA, LPP-FFA. A better understanding of pruritus and its accompanying symptoms can help in choosing an appropriate and effective therapeutic option.
P61
Title:
Drugs
inducing generalized non-allergic pruritus without skin lesions: data
from VigiBase, the worldwide pharmacovigilance database
Submitting
author:
Kondor, Lucie - Laboratory Interactions
Neurons-Keratinocytes (LINK), UR4685, University of Western Brittany,
Brest (France)
Abstract:
Objective: Analyze pharmacovigilance data to identify drugs frequently associated with generalized, non-allergic pruritus without skin lesions. Methods: Data were extracted from VigiBase, the WHO global pharmacovigilance database. Inclusion criteria were cases of generalized pruritus linked to a single suspected systemic drug. Cases including terms related to allergic, dermatological or renal failure were excluded. A second analysis focused on cases with positive rechallenge (when pruritus reappeared with a drug reintroduction). A descriptive analysis of patient demographics and an assessment of drug classes based on the numbers of cases were performed. Results: A total of 268,799 case were identified. More cases affected women (61.4%). The age classes most represented were the 45-64 years old (30.7%). The American regions declared the highest proportion of cases (35.8%). The majority of cases were reported by physicians (31.7%) and the majority of declarations were spontaneous reports (90.9%). The most represented drug classes were antibacterials, vaccines, immunosuppressants, contrast media, anticancer agents and then opioids. A subset of 3,847 positive rechallenge cases reinforced causality for antibiotics, opioids, non-steroidal anti-inflammatory drug and emerging drug classes such as statins and antacids. Conclusion : Antibiotics (quinolones, beta-lactams, and sulfonamides) were the most frequently involved drug class. COVID-19 vaccines were also commonly reported. Statins and antacids emerged as potential inducers of pruritus. The strengths of this study include the large pharmacovigilance dataset analyzed and the specific focus on generalized, non-allergic pruritus without skin lesions. This global pharmacovigilance analysis highlights the drugs most frequently associated with pruritus, thereby helping clinicians recognize and manage drug-induced pruritus more effectively.
P62
Title:
Itch
Beyond the Surface: Dermoscopic-Histopathological Correlation in 66
Cases of Prurigo Nodularis in Skin of Colour
Submitting
author:
Palaniappan, Vijayasankar - Assistant Professor,
Department of Dermatology, Sri Manakula Vinayagar Medical College and
Hospital, Pondicherry, India
Abstract:
Introduction Prurigo nodularis (PN) is a chronic, intensely pruritic skin condition that significantly affects quality of life. In individuals with skin of colour, its diagnosis can be delayed due to less obvious clinical signs. This study investigates the dermoscopic and histopathological features of PN, aiming to improve diagnostic accuracy in pigmented skin. Objectives • To describe the clinical, dermoscopic, and histopathological characteristics of prurigo nodularis • To assess correlations between dermoscopic patterns and underlying histopathological changes Methodology This cross-sectional study was carried out between June 2020 and August 2024 at a tertiary care dermatology centre in South India. Sixty-six patients with biopsy-proven prurigo nodularis were included. Dermoscopic evaluation was performed using a polarized DermLite DL4 device. Pruritus severity was measured using the Visual Analogue Scale (VAS). Correlations between dermoscopic and histological features were analyzed using appropriate statistical methods. Results The study included 66 patients (mean age: 34.1 ± 18.3 years); 54.5% were female. Pruritus was moderate in 53%, severe in 36.4%, and very severe in 10.6%. Frequently affected areas included the legs (68.2%), dorsum of the feet (47%), and forearms (37.9%). Histopathological findings included vertically oriented collagen bundles (92.4%), acanthosis (89.4%), compact orthokeratosis (84.8%), and hypergranulosis (89.4%). Dermoscopy revealed peripheral striations (90.9%), white starburst patterns (86.4%), pearly white areas (86.4%), and red globules (83.3%). Notably, peripheral striations correlated with vertically aligned collagen; starburst and pearly white areas with epidermal hyperplasia; and red globules with dilated dermal vessels. Conclusion This study provides valuable insights into the dermoscopic presentation of prurigo nodularis in skin of colour. Strong correlations between dermoscopic features and histological findings support the use of dermoscopy as a non-invasive tool to aid diagnosis. By identifying reliable visual markers i
P63
Title:
Clinical
characterization of cholestatic pruritus and its impact on quality of
life; a cross-sectional study
Submitting
author:
Papanikolaou, Marieta - Dr. Phillip Frost Department of
Dermatology and Cutaneous Surgery University of Miami Miller School
of Medicine, 1600 NE 10th Ave, RMSB 2040-A Miami, Florida 33136
Additional
Authors:
Ashley Vander Does 1, Leigh Nattkemper 1, Elise Edwards
1, Nicole Khalil 1, Georgia B Soares 1, Sarah G Brooks 1, Brysen
Keith 2, Cynthia Levy 2, Gil Yosipovitch 1 1Dr. Phillip Frost
Department of Dermatology and Cutaneous Surgery, Miami Itch Center,
Miller School of Medicine, University of Miami, Miami, Florida,
United States 2Division of Digestive Health and Liver Diseases,
University of Miami Miller School of Medicine, Miami, Florida, United
States
Abstract:
Itch is the most frequent symptom of cholestasis, affecting up to 80% of patients. Despite recent advances in our understanding of cholestasis and itch pathophysiology, cholestatic pruritus remains a therapeutic challenge. The present study aimed to characterize clinical features and patient-reported impact of cholestatic pruritus in primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). Adult patients on standard therapy were recruited during routine visits at University of Miami Hepatology clinics between March 2022 and May 2024, excluding those with other primary causes of itch. Itch was assessed using 24-hour average and worst Numerical Rating Scale (aNRS and wNRS), and the 5D itch scale. Quality of life (QoL) questionnaires PBC-40 and ItchyQoL were completed. Thirty-five patients were recruited: 25 with and 10 without itch. The itchy cohort comprised 18 PBC and 7 PSC subjects. Out of 35, most (80%) received ursodeoxycholic acid. Other treatments included cholestyramine (20%), azathioprine (11%), corticosteroids (9%), antihistamines (6%) and FXR agonists (6%). The mean±SD for aNRS, wNRS, 5D and ItchyQol was 4.4/10±2.4, 5.1/10±2.5, 13.3/25±4.7 and 51.3/110±21.4 respectively. Eighteen (72%) patients had moderate/severe itch based on aNRS, while 19(76%) reported disturbed sleep and 12(48%) bleeding secondary to itch. Twelve of 25 patients with pruritus were followed up after an average of 8 months (range 3-18). There was no difference in itch or QoL scores between baseline and follow-up visits. Itch metrics did not differ between PSC and PBC; however, palmoplantar surfaces were affected in a higher proportion of PBC subjects (67%vs29%, P 0.0577). Compared with non-itchy patients, those with itch had higher average scores across all PBC-40 domains, with most profound impact on social function (P 0.0069). These results highlight the high prevalence and major impact of cholestatic itch among PBC and PSC patients, which remain to be addressed. Validation in larger patient cohorts is required.
P64
Title:
Serum
D-Dimer as a Surrogate Biomarker for Itch Severity Across Chronic
Pruritic Dermatoses: A Cross-Sectional Exploratory Study
Submitting
author:
Rathi, Parth - Department of Dermatology, VMMC &
Safdarjung Hospital, New Delhi, India.
Abstract:
Background: Chronic itch is a debilitating symptom that spans diverse dermatologic and systemic disorders, yet remains challenging to quantify and manage. Recent evidence suggests that systemic inflammation may play a central role in itch pathophysiology. D-dimer, a marker of coagulation and inflammatory activation, may serve as a novel, objective correlate of itch severity across conditions. Objective: To evaluate serum D-dimer levels in patients with chronic pruritic dermatoses and investigate its correlation with itch severity and disease type. Methods: A cross-sectional observational study was conducted among 60 adult patients presenting with chronic itch due to various conditions (e.g., chronic spontaneous urticaria, atopic dermatitis, psoriasis, lichen planus, chronic kidney disease–associated pruritus). Pruritus severity was quantified using both the 5-D Itch Scale and a Visual Analog Scale (VAS). Serum D-dimer levels were measured and analyzed for correlation with itch scores and across diagnostic categories. Results: Across all conditions, mean D-dimer levels showed a strong positive correlation with itch intensity (r = 0.62 for 5-D Itch, r = 0.58 for VAS; p < 0.001). CSU and atopic dermatitis patients demonstrated the highest D-dimer levels, aligning with more severe reported pruritus. Notably, 40% of patients with elevated D-dimer reported nocturnal itch, suggesting systemic involvement. Differences in D-dimer levels between disease groups were statistically significant (ANOVA, p < 0.01). Conclusion: D-dimer may serve as a useful surrogate biomarker for systemic itch severity, offering an objective parameter to complement subjective itch scoring tools. Its elevation in CSU and atopic dermatitis highlights a shared inflammatory–coagulopathic axis, opening new avenues for monitoring and targeted interventions in chronic pruritus.
P65
Title:
The
importance of immunofluorescence investigations in elderly patients
with chronic pruritus and skin lesions
Submitting
author:
Schadelbauer, Eva - Department of Dermatology and
Venereology, Medical University of Graz, Graz, Austria
Additional
Authors:
Riegler M.1, Gruber V.1, Schirl C.1, Repelnig M.1,
Sauseng C.1, Legat FJ.1 1. Department of Dermatology and Venereology,
Medical University of Graz, Graz, Austria
Abstract:
Background: Pruritus, recognized as the most prevalent symptom in dermatology, profoundly affects quality of life and is a cardinal feature of diverse cutaneous and systemic diseases. Chronic pruritus, affecting up to 22% of the population1, frequently poses diagnostic and therapeutic challenges, particularly when clinical and histopathological findings are nonspecific. Objectives: To highlight the importance of itch in dermatological practice and demonstrate the need for advanced diagnostics in patients with chronic pruritic dermatoses of unclear etiology, with an emphasis on the potential overlap between prurigo and autoimmune bullous disorders. Methods: Three elderly patients presenting with chronic pruriginous lesions underwent comprehensive diagnostic evaluation, including skin biopsies and immunofluorescence (IF) studies. Only cases with photographic documentation were included. Results: Among the three cases [1F (82a), 2M(82a, 78a)], histopathological analysis revealed heterogeneous findings: Grover’s disease, chronic prurigo, eczematous dermatitis and/or hypersensitivity reaction. Indirect IF(IIF) was performed in all patients: two were positive (A:BP230+, Split Skin+; B:BP180+, BP230+, Split Skin+); one was negative, however, was positive in direct IF(DIF). DIF was performed in two patients and showed IgG or C3 deposition at the dermo-epidermal junction, consistent with a bullous pemphigoid pattern. One was also positive in IIF. Conclusions: These cases illustrate a distinct subset of elderly patients with chronic pruritus who exhibit overlapping serological and histopathological features of pruriginous skin lesions and autoimmune bullous dermatoses. Our findings underscore the importance of IF in chronic unexplained pruritic dermatoses, possibly leading to a diagnosis of underlying autoimmune disease. Identification of specific immunopathological markers may inform targeted therapy, including agents effective in autoimmune blistering disorders. Awareness of such overlaps may be crucial for management of clinically atypical pruritic dermatoses in daily practice.
P66
Title:
Alterations
of epidermal innervation in psoriatic skins
Submitting
author:
Talagas, Matthieu - Laboratory on Interactions Neurons
Keratinocytes, Univ. Brest, Brest, France
Abstract:
The presence of pruritus in 80% of psoriatic patients, the regression of psoriatic lesions following nerve damage or, conversely, their exacerbation under the influence of stress suggest an involvement of the nervous system, via intraepidermal nerve fibres (IENFs), in the pathophysiology of psoriasis. However, literature data remain contradictory regarding the density of IENFs in psoriatic lesions. Skin biopsies were obtained from lesional (L) and non-lesional (NL) skins of 23 psoriatic patients. IENFs density was measured by immunostaining using anti-PGP9.5 antibody. IENFs branches, keratinocyte and neuronal synaptophysin+ presynaptic vesicles (PV) were quantified by confocal microscopy. Expressions of synaptic protein transcripts (synaptophysin, synaptotagmin 1, syntaxin 1A) were assessed by RT-qPCR. Our results showed a significant decrease in IENFs density (167±148 vs 264±186/mm2) and in the number of branches (0.39±0.38 vs 1.34±0.72/100µm of IENFs) in L compared to NL, independently of pruritus. The number of PV in keratinocytes in contact with IENFs (0.14±0.08 vs 0.21±0.11/µm IENFs) and the area of synaptophysin+ staining in IENFs (0.12±0.05 vs 0.25±0.1) were also significantly reduced in L. RT-qPCR results supported these results. The density of keratinocyte PV was negatively correlated with IENFs density. No correlation was found between pruritus and the various parameters evaluated. The reductions of IENFs density and nerve branches in psoriatic lesions shed new light on the pathophysiology of psoriasis. Pruritus occurs independently of any epidermal hyperinnervation as usually described in the literature. Keratinocytes and FNEs act as a two-site sensory receptor. The negative correlation between keratinocyte PV density and FNEs density in NL argues for the existence of such pair in physiological condition. The decrease in keratinocyte PV density in L compared to NL argues for a reduction in the activity of keratinocyte-sensory neuron synapses in L. Pruritus associated with psoriasis might thus be due to neuronal sensitization independent of synapses.
P67
Title:
Multi-omics
Reveals CCL3 Driving Neuronal Sensitization in Chronic Pruritus of
Unknown Origin
Submitting
author:
Wang, Fang - Dermatology Hospital of Southern Medical
University, 2 Lujing Road, Guangzhou, Guangdong, China
Abstract:
Introduction: Chronic pruritus is a pathological condition associated with numerous systemic, dermatologic, and neurologic disorders. Chronic pruritus of unknown origin (CPUO) represents a distinct clinical subtype characterized by persistent itch without an identifiable underlying cause. While emerging evidence implicates neuroimmune dysregulation in chronic pruritus, the specific mechanisms driving CPUO remain poorly understood. Objectives: To characterize the neuroimmune mechanisms underlying CPUO, with a focus on identifying potential diagnostic markers. Methods: Baseline itch severity (numerical rating scale) and laboratory parameters were assessed in 35 CPUO patients. Single-cell RNA sequencing of peripheral blood cells from patients and healthy controls was integrated with plasma proteomic profiling of 117 inflammatory mediators using ELISA and LEGENDplex assays. Murine itch behavioral assays, immunofluorescence staining, and calcium imaging of sensory neurons were conducted. Results: Single-cell transcriptomic analysis revealed dysregulated monocytes and hyperactive natural killer (NK) cells overexpressing CCL3. Plasma CCL3 levels effectively distinguished CPUO patients from healthy controls (AUC = 0.835) and correlated with itch severity (r = 0.49, P = 0.015). Although CCL3 did not directly evoke itch behavior in mice, it enhanced neuronal responses and exacerbated itch behavior in response to pruritogens, including β-alanine, chloroquine, leukotriene C4, and histamine, via CCR1. Pharmacological inhibition of CCR1 with BX471 significantly abolished this neuronal sensitization effect. Conclusion: CPUO involves distinct neuroimmune alterations, with CCL3 emerging as a potential diagnostic biomarker. The CCL3-CCR1 axis links immune dysregulation to neuronal hypersensitivity, providing a possible therapeutic target.
P68
Title:
Neuroanatomy
of chronic prurigo under dupilumab treatment
Submitting
author:
Witte, Felix - Department of Dermatology, Section
Pruritus Medicine and Center for chronic pruritus, University
Hospital Münster, Münster, Germany
Additional
Authors:
Claudia Zeidler1, Henning Wiegmann1, Anna Brenske1,
Svenja Royeck1, Konstantin Agelopoulos1, Sonja Ständer1 1Department
of Dermatology, Section Pruritus Medicine and Center for chronic
pruritus, University Hospital Münster, Münster, Germany
Abstract:
Introduction Itch is the dominant and most burdensome symptom in chronic prurigo (CPG) patients. With dupilumab, a biologic treatment has recently been approved for the treatment of moderate to severe CPG, demonstrating favorable effects on skin lesions and itch. However, cutaneous neuronal alterations underlying itch in CPG and their development during treatment are still poorly understood, whilst data point to a reduced intraepidermal nerve fiber density (IENFD) in CPG lesions compared to healthy controls.1 Data from atopic dermatitis patients offer promising results regarding an improvement in IENFD following dupilumab treatment.2 Objectives Deciphering cutaneous neuronal alterations during CPG treatment with dupilumab. Methods Skin biopsies and blood from adult patients with moderate to severe CPG receiving dupilumab 300mg subcutaneously every two weeks over a period of 16 weeks were analyzed at initial assessment (IA) and at follow-up (FU, week 16) for IENFD, alloknesis and biomarker, next to clinical outcome parameters. This study is still recruiting, the planned cohort size is n = 50. Results Preliminary data of 25 patients reveal a significant improvement of itch intensity (WI-NRS/24h, p < 0.001) and quality of life (DLQI, p = 0.001) after 16 weeks of dupilumab treatment. Clinical improvement was paralleled by a significant improvement of IENFD (n = 21 subjects) from BL lesional skin to FU former lesional skin (p = 0.003). Conclusions Preliminary data point towards a neuroanatomical response to dupilumab treatment in CPG, with nerve fiber regeneration paralleling itch reduction. 1 Pogatzki-Zahn et al., J Invest Dermatol. 2020 2 Wiegmann, Witte et al., in revision
P69
Title:
Optical
Coherence Tomography Angiography Reveals Distinct Vasodilation
Patterns in Histamine and Cowhage-Induced Itch
Submitting
author:
Arendt-Nielsen, Lars - 1. Center for Neuroplasticity and
Pain (CNAP), Department of Health Science and Technology, School of
Medicine, Aalborg University, Gistrup, Denmark
Additional
Authors:
Trine Andresen1, Katrine Nørgaard Behrentzs1, Sofie
Søndergaard Laursen1, Emilie Krabbe Brandt1, Stine Skov Kjeldbjerg
Frederiksen1, Victoria Englund-Sørensen1, Lydia Haggard2, Gavrielle
Untracht2, Christian Stevns Hansen3, Pall Karlsson4, Johan Møller
Røikjer5, Peter Andersen2, Carsten Dahl Mørch1, Lars
Arendt-Nielsen1* 1. Center for Neuroplasticity and Pain (CNAP),
Department of Health Science and Technology, School of Medicine,
Aalborg University, Gistrup, Denmark 2. Dept. Health Tech, Technical
University of Denmark, Denmark 3. Steno Diabetes Center Copenhagen,
Copenhagen University Hospital, Denmark 4. Danish Pain Research
Center, Dept. Clin. Med. Aarhus University, Denmark 5. Steno Diabetes
Center North Jutland, Aalborg University Hospital, Denmark *
Presenter
Abstract:
Background: Itch can be broadly categorized into histaminergic and non-histaminergic types, each mediated by distinct molecular and neural pathways. Non-histaminergic itch is provoked via PAR2 and PAR4 receptors and activated by substances like cowhage (Mucuna pruriens). Cowhage spicules contain mucunain, a cysteine protease, making cowhage a well-established model non-histaminergic itch. When assessing neurogenic inflammation quantitatively by e.g. Laser Speckle or Doppler Imaging, increased blood flow/flux are found after histamine provocation, but not after cowhage application. Optical coherence tomography (OCT) can image small tissue structures and rapidly repeated scanning allows assessment of cutaneous vascularization i.e., angiography. Objectives: The study aimed to assess and compare the vascular response to histamine and cowhage using OCT-Angiography. Methods: OCT-A recordings were obtained before and after application of histamine and cowhage to separate sites on the volar forearm and compared to a non-treatment area. The vascular area density (VAD) in the capillary dermis and reticular dermis was quantified and compared between histamine and cowhage. Results: Twenty healthy participants completed the study. In the capillary layer, histamine (3.2%+/-0.1%) and cowhage (3.2%+/-0.1%) caused similar VAD, which was higher than the non-treated area (1.8%+/-0.1%; MLM p<0.0001). In the reticular layer, histamine caused a higher VAD (27%+/-0.6%) than cowhage (20.1%+/-0.6%) which were both higher than the non-treatment area (15.9%+/-0.5%; MLM p<0.0001). Conclusion: This study demonstrated that both histamine and cowhage increased vasodilation in the skin. The significantly greater VAD observed in the reticular dermis following histamine application, compared to cowhage, highlights distinct vascular activation patterns. These findings support the utility of OCT-A as a non-invasive tool for differentiating itch mechanisms and may contribute to the fundamental understanding of how PAR2/PAR4 containing C-polymodal afferents provoke microcirculatory responses and may be crucial for development of targeted therapies for nonhistaminergic itch conditions.
P70
Title:
Pruritus
in a cohort of occupational dermatological patients suffering from
atopic dermatitis and psoriasis
Submitting
author:
Bentz, Philipp - Divison of Occupational Dermatology,
Heidelberg University Hospital, Voßstraße 2, 69115 Heidelberg,
Germany
Additional
Authors:
Prof. Dr. Elke Weisshaar (Divison of Occupational
Dermatology, Heidelberg University Hospital, Voßstraße 2, 69115
Heidelberg, Germany)
Abstract:
Atopic dermatitis (AD) and psoriasis are chronic, inflammatory skin diseases. Clinically, they show overlapping features, which can complicate precise diagnosis and influencing treatment decisions. Both diseases frequently occur in occupational dermatological patients. Pruritus is the main symptom leading to a high disease burden in these patients. It often results in sleep loss, an overall reduction of quality of life (QoL), can act as a chronic stressor and/or cause psychological comorbidities. In 2020, an occupational dermatological cohort (N=287) was established that aims to investigate the impact of a new molecular diagnostic on diagnostic precision and the progression of associated factors like disease course and severity, treatment decisions, job retention or QoL. Patients reported acute and chronic pruritus (CP) (> 6 weeks), intensity (none, mild, moderate, severe, very severe) and localization of pruritus. Patients are followed-up after 6 months, then once a year. The disease duration ranged from <1 year up to 47 years (mean: 5.5 years; SD: 7.9). 16.4% of patients reported having a skin disease for ten or more years. 57.3% (n=165) had acute pruritus at baseline, 75% of which were chronic pruritus (CP) patients. 53.8% (n=155) reported having CP within the previous 12 months.AD patients did not suffer from CP significantly more often than psoriasis patients (AD: 52.5% vs. psoriasis: 47.8% prevalence). The duration of the skin disease was not associated with the frequency of CP. In CP patients, pruritus was more often sever/very severe (41.9%) than in patients with acute pruritus (16.2%), which showed a significant and strong correlation (χ²=92.5, p < .0005, V=0.57). However, severity was not significantly higher in eczema patients. Acute and chronic pruritus is also prevalent in occupational skin diseases with high disease burden, unmediated by diagnosis or duration of skin disease. This is especially relevant, since scratch lesions can further worsen the skin disease and therefore hinder optimal healing.
P72
Title:
Estimates
of prevalence and comorbidities of patients with chronic pruritus of
unknown origin: A retrospective cross-sectional analysis of two US
claims databases
Submitting
author:
Elmariah, Sarina - UCSF Center for Itch and Neurosensory
Disorders, University of California, San Francisco, CA, USA
Additional
Authors:
Shawn G. Kwatra/ Department of Dermatology, University
of Maryland School of Medicine, Baltimore, MD, USA Meghan Richards/
Merative, Ann Arbor, MI, USA Nicole Princic/ Merative, Ann Arbor, MI,
USA Zarif K. Jabbar-Lopez/ Galderma, Zug, Switzerland Lorenzo
Sabatelli/ Galderma, Zug, Switzerland Christophe Piketty/ Galderma,
Zug, Switzerland
Abstract:
Introduction: Chronic pruritus of unknown origin (CPUO) is defined as pruritus lasting >6 weeks without an identified cause. Very limited data are available on its prevalence and related healthcare burden. This study estimated prevalence, and described comorbidities as well as treatment patterns of patients with diagnoses compatible with CPUO in US-based claim databases. Methods: Patients with continuous medical and pharmacy benefits between 1 January 2022 and 31 December 2022 were identified using the MarketScan® Commercial and Medicare Databases. Patients with CPUO were identified as those with ≥2 claims for pruritus unspecified (L29.9) at least 90 days apart. A sensitivity analysis using the same inclusion and exclusion criteria but including also patients with the ICD-10 code L29.8 (other pruritus) was performed. All categorical variables were presented as counts and percentages. Results: In the year 2022, 5,774 patients were identified by the main analysis, resulting in a prevalence of 36.7 per 100,000 persons (potentially corresponding to a total of 122,317 patients nationwide, based on a national population of 333,287,557). The sensitivity analysis found 15,278 patients, i.e. 97.1 per 100,000 persons (projecting 323,622 patients nationwide). Median age was 55 years and 64.9% were female. Common comorbid conditions included hypertension (40.0%), arthralgia (26.4%), and allergic rhinitis (25.0%). Topical and/or oral corticosteroids, antidepressants, and gabapentin were the most frequently prescribed treatments. Conclusion: While its exact prevalence in the US remains uncertain, CPUO was identified in a non-negligible proportion of the US population captured in the studied databases and is associated with several comorbidities which increase the overall disease burden. Study limitations include the limited/incomplete patient information contained in claims, and the non-specificity of ICD-10 codes utilized to identify CPUO (which may lead to an overestimation of prevalence). Further studies are required to better understand the relationship between CPUO and comorbidities.
P73
Title:
Prevalence
and burden of chronic kidney disease-associated pruritus in Europe
(CENSUS-EU)
Submitting
author:
Gallieni, Maurizio - Department of Biomedical and
Clinical Sciences, University of Milan, Milan, Italy
Abstract:
Introduction/Objectives: Chronic kidney disease-associated pruritus (CKD-aP) is common and can impair health-related quality of life (HRQoL). Despite this, there has been a lack of clarity on its prevalence and impact. Methods: CENSUS-EU is a real-world, cross-sectional, multicenter study in Europe, which aimed to assess the prevalence of CKD-aP and its impact on HRQoL in adult patients receiving hemodialysis. Patients completed questionnaires on pruritus presence/severity (the Worst Itching Intensity Numerical Rating Scale), and HRQoL (including the 5‑D itch scale and the integrated palliative care outcome scale symptom list for end-stage renal disease). Medical records were used to gather information on dialysis, treatment, and healthcare resource use. Data were analyzed by pruritus severity (no, mild, moderate, and severe). Results: Data were evaluated for 2,963 patients. Patients had a mean age of 66.2 years and 62.7% were male. Overall, the prevalence of CKD-aP was 53.5%; 22.3% of patients experienced mild, 18.0% moderate, and 13.2% severe pruritus. As pruritus severity increased from no pruritus to severe pruritus, patients reported more difficulty sleeping and feelings of depression. 5-D itch disability subscale scores also increased with pruritus severity. Patients with severe pruritus were hospitalized more often than those with mild or moderate pruritus (2.1 versus 1.8 and 2.0 times/patient/year, respectively). The proportion of patients receiving ≥1 ongoing anti-itch treatment increased with pruritus severity but remained low in all subgroups (18.3%, 25.3%, and 39.9% of patients with mild, moderate, and severe pruritus, respectively). Conclusion: In this study, a third of patients on hemodialysis experienced moderate or severe pruritus, and HRQoL decreased with pruritus severity.
P74
Title:
Addressing
the post-burn pruritus. A systematic review on incidence and
pharmacological management for post-burn pruritus.
Submitting
author:
Neupane, Nischal - Institute of medicine, Department of
Dermatology, Maharajgunj, Kathmandu, Nepal
Abstract:
Nischal Neupane1, Devansh Upadhyay1, Prajjwol Luitel1 1. Institute of Medicine, Tribhuvan University Teaching Hospital Post-burn pruritus is a common distressing complication during burn recovery, affecting both pediatric and adult populations. Despite its significant prevalence, there is no gold standard treatment. We conducted a systematic review to synthesize current evidence on incidence and management for post-burn pruritus. To evaluate the incidence and effectiveness of various pharmacological management strategies for post-burn pruritus across different age groups. A systematic search was conducted across databases including PubMed and Scopus for studies in English. Prospective, retrospective studies, open labelled trial, and case series reporting on the incidence, treatment, and outcomes of post-burn pruritus regardless of publication year, patient age, demographics, geographic location were included. Data were extracted on study design, population, interventions, assessment tools, and treatment outcomes. A total of 9 studies (n = 286) met inclusion criteria. Studies were from 2008 to 2022. The overall mean age was 23.63 years ranging from 2.56-43.3 years. TBSA ranged from 3.5-60% with an overall mean TBSA of 21.82%. Incidence of pruritus was reported in three studies and ranged from 37.3-71.7%. Antihistamines such as diphenhydramine and loratadine were commonly used as first-line agents. Gabapentin and pregabalin demonstrated significant symptom reduction in randomised trials (e.g., VAS- visual analogue scale reduction from 6.3 to 0.3, p < 0.01). The Toronto Pediatric Itch Scale, Itch Man Scale, and Visual Analogue Score were the primary assessment tools. Incidence of pruritus ranged from 37.3%-71.7%, with chronic pruritus reported in up to 10% of cases. Current evidence supports the use of gabapentinoids and antihistamines in managing post-burn pruritus, particularly when combined with supportive non-pharmacologic measures. However, heterogeneity in assessment tools and treatment protocols highlights the need for standardized guidelines.
P75
Title:
Acne
Itch Revisited
Submitting
author:
Szepietowska, Marta - Wroclaw Medical Unievrsity,
Wroclaw, Poland
Abstract:
Background: Chronic itch is a common symptom of inflammatory skin diseases. This study was undertaken to evaluate the presence and intensity of itching in two different cohorts of acne subjects. Additionally, the influence of itching on the psychosocial status of acne individuals was assessed. Methods: Consecutive acne patients seeking dermatological advice and university students diagnosed with acne during dermatological screening were considered. The clinical and psychological aspects of acne were assessed using a variety of instruments. Results: About 40% of acne subjects in both cohorts reported itching. The mean WI-NRS during the last 3 days in acne patients was 3.83 ± 2.31 points (mild itch) and was significantly more severe (p < 0.001) than in university students diagnosed with acne (2.09 ± 1.29 points). Itch intensity did not depend on the clinical severity of acne. In consecutive acne patients, itch intensity correlated with quality-of-life impairments (assessed using DLQI and CADI) and HADS scores. There was no correlation between itch intensity and stigmatization levels. Conclusions: Itching seems to be a common phenomenon in acne sufferers. Acne itch significantly influences patients' well-being and should be considered in a holistic approach to acne patients.
P76
Title:
Chronic
Itch in Ukraine During the Military Conflict
Submitting
author:
Szepietowski, Jacek C - Division of Dermatology,
Venereology and Clinical Immunology, Faculty of Medicine, Wroclaw
University of Science and Twechnology
Abstract:
Chronic Itch in Ukraine During the Military Conflict Jacek C Szepietowski1,2, Katarzyna M Jankowska2, Dimitry Bashmakov3, Piotr K Krajewski4, Tatyana Svyatenko3 1Division of Dermatology, Venereology and Clinical Immunology, Faculty of Medicine, Wroclaw University of Science and Technology, Wroclaw, Poland; 2Department of Dermato-Venereology, 4th Military Hospital, Wroclaw, Poland; 3Department of Skin and Venereal Diseases, Dnipro State Medical University, Dnipro, Ukraine 4NuvaMed Medical Center, Wroclaw, Poland Introduction: Chronic itch (CI) is a burdensome symptom with multifactorial origins, including dermatological, systemic, neurological, and psychological causes. War-related stress may significantly alter the profile of CI in affected populations. Objective: To evaluate and compare the causes and characteristics of chronic itch among Ukrainian soldiers and civilians during the military conflict. Methods: A total of 210 patients with CI were enrolled (77 soldiers and 133 civilians). CI was classified according to the International Forum for the Study of Itch (IFSI) guidelines. The intensity of itch was assessed using an 11-point Numerical Rating Scale (NRS). Results: Psychological itch was the most common cause among soldiers (44.1%), while dermatological itch predominated in civilians (63.2%). Soldiers primarily reported itch on non-diseased skin (68.8%), whereas civilians commonly presented with itch on diseased skin (64.7%) (p<0.001). The mean NRS score was significantly lower in soldiers (3.42 ± 1.53 points) compared to civilians (5.48 ± 1.87 points) (p<0.001). CI duration was also shorter in the military group. Conclusion: Psychogenic itch predominates among soldiers exposed to war-related stress.
P77
Title:
Pruritus:
a Systematic Review evaluating Content Validity of Patient-Reported
Outcome Measures
Submitting
author:
van de Burgt, Emmy - Department of Experimental
Psychology, University of Groningen, Grote Kruisstraat 2/1 9712 TS
Groningen, The Netherlands
Abstract:
Introduction Chronic pruritus can significantly impact patients’ quality of life, but it is difficult to measure due to its subjective nature. Although many Patient-Reported Outcome Measures (PROMs) have been developed to assess itch intensity and its effects, it remains unclear whether these tools truly reflect what matters most to patients. This is concerning—if a PROM lacks strong content validity, both research findings and clinical decisions may be based on incomplete information. Even though content validity is a key part of PROM development, it is often overlooked or inconsistently reported in studies. Objective To identify, summarize, and systematically evaluate the evidence of content validity of PROMs developed for assessing pruritus in adult patients. Methods This review was conducted following the Consensus based Standards for selection of health Measurement Instruments (COSMIN) methodology for assessing content validity. Three electronic databases (PubMed, EMBASE and CINAHL) were searched from inception until September 9, 2023. Study selection, data extraction, and assessment of methodological quality and content validity (relevance, comprehensiveness, and comprehensibility) were performed independently by two authors. Results Thirty-nine studies evaluating 22 PROMs were included: six unidimensional and sixteen multidimensional. Only one unidimensional PROM (Itch-NRS, in four versions) and ten multidimensional PROMs had any evidence of content validity. The methodological quality of these studies was mixed, and many lacked patient involvement in item development. However, the increasing application of COSMIN methodology in recent years marks a significant advancement in the field. Conclusions This review provides a comprehensive overview of the content validity of PROMs used in pruritus research and care. The findings support more informed selection of PROMs by clinicians and researchers and highlight areas where further development or refinement of PROMs is needed.
P78
Title:
Thoughts
on the epidemiology of chronic prurigo
Submitting
author:
Waitek, Maurice - Division of Occupational Dermatology,
Department of Dermatology, University Hospital Heidelberg,
Heidelberg, Germany
Additional
Authors:
Elke Weisshaar, MD, PhD / Division of Occupational
Dermatology, Department of Dermatology, University Hospital
Heidelberg, Heidelberg, Germany
Abstract:
Chronic prurigo (CPG) has garnered more and more attention in the last years. Epidemiological studies have been conducted as a result. Prevalences vary widely between studies, but are generally low, with the worldwide prevalence being estimated at 0,083%. Older patients are more commonly affected by CPG. In Western studies there is a female predominance, whereas Asian studies reported higher numbers of male patients. African-Americans seem to suffer more frequently from CPG than Caucasians. These studies give new information, but there is still a need for more research in this field: There are no studies from Africa, South America or Oceania, meaning a possibly underestimated global prevalence. Whether sex differences play a role in CPG remains unclear. There was no clear disease definition until 2018 and CPG is still difficult to diagnose and treat. Patient- and physician-reported outcome measures on CPG are scarce. The existing studies also differ regarding these outcome measures, regarding disease definition and were mostly register-based with data from before 2018. Studies investigating CPG in the general population remain missing. In many studies, prevalence estimates are not characterised (point-, 1-year, lifetime prevalence). Future studies should address these issues and aim for a clear and comparable assessment of CPG, regarding different prevalences, the incidence of CPG, comorbidities and ethnic and sex differences.
P79
Title:
Evaluating
the Utility of Extracorporeal Shock Wave Therapy for Burn Pruritus: A
Systematic Review and Meta-Analysis
Submitting
author:
Yadav, Rukesh - District Hospital Dhankuta, Internal
Medicine, Dhankuta city, Nepal
Abstract:
Introduction:
Burn pruritus is a common and distressing sequela in burn survivors, significantly impairing quality of life and hindering rehabilitation. Conventional pharmacologic and non-pharmacologic treatments often provide limited relief. Extracorporeal shock wave therapy (ESWT), a non-invasive modality known for its regenerative and neuromodulatory properties, has emerged as a potential intervention.
Objectives:
This systematic review and meta-analysis aimed to evaluate the efficacy and safety of ESWT in managing burn-related pruritus.
Methods:
A comprehensive search was conducted in PubMed, Embase, Cochrane Library, and clinical trial registries from inception to April 2025. Studies assessing ESWT for pruritus in burn patients were included. Primary outcomes were pruritus severity, assessed using validated scales (e.g., Visual Analog Scale [VAS], Itch Severity Scale, Numerical Rating Scale). Risk of bias was assessed using the Cochrane RoB 2.0 and Newcastle-Ottawa Scale. A random-effects meta-analysis was performed.
Results:
Four studies involving a total of 82 burn patients and 66 healthy controls were included. Meta-analysis including three studies demonstrated a significant reduction in pruritus severity with ESWT compared to control or sham therapy (mean difference [MD]: –1.99; 95% CI: –3.72 to –0.27; p =0.02; I² = 88%) (figure 1). Improvements were consistent across different ESWT protocols and burn types. ESWT use duration ranged from one to six months. There was significant reduction in pruritus post ESWT as compared to baseline ([MD]: 3.01; 95% CI: 1.71 to 4.30; p =0.0001; I² = 88%) (figure 2).
Conclusion:
ESWT appears to be a promising, safe, and effective non-invasive intervention for reducing burn pruritus. However, further large-scale, standardized trials are warranted to confirm these findings and to optimize treatment parameters. Incorporating ESWT into multidisciplinary burn rehabilitation programs may enhance long-term outcomes and patient satisfaction.
P80
Title:
Device-based
physical therapies in chronic pruritus: An overview
Submitting
author:
Zhu, Jie - Department of Dermatology, University
Hospital Basel, Basel, Switzerland
Abstract:
Author: Jie Zhu, Xuanyu Zhao, Alexander A. Navarini, Simon M. Mueller Affiliation: Department of Dermatology, University Hospital Basel, Basel, Switzerland. Introduction: Chronic pruritus (CP) is a highly prevalent disease associated with high psychosocial and economic burdens. In addition to pharmacological treatments, device-based physical therapies also offer antipruritic effects. Objectives: To provide an overview of device-based physical treatment options (including phototherapy, laser treatment, electrical neurostimulation technologies, acupuncture, cryotherapy, and cold atmospheric plasma) and their roles in the management of chronic pruritus. Methods: We conducted a narrative review of the literature using the PubMed database, focusing on peer-reviewed articles published in English up to 2024. Initial searches were performed using specific keywords such as “phototherapy,” “physical therapy,” “laser,” and “pruritus” or “itch.” For less well-defined modalities—such as electrical neurostimulation technologies, acupuncture, cryotherapy, and cold atmospheric plasma—we first identified relevant therapies through broader reviews or clinical resources, followed by more targeted searches for each modality. Results: Phototherapy, laser treatment, electrical neurostimulation technologies, acupuncture, cryotherapy, and cold atmospheric plasma are, in part, still experimental but emerging treatment options that augment our repertoire to treat patients with chronic pruritus. Conclusion: Clinicians should be aware of these device-based treatments and integrate them into the management of CP where appropriate.
P81
Title:
Pharmacological
targeting of pruriceptors in pigs
Submitting
author:
Abbasi, Zeinab - Department of Experimental Pain
Research, Mannheim Center for Translational Neuroscience, Medical
Faculty Mannheim, Heidelberg University, Germany
Abstract:
Z. Abbasi1, M. Behrendt1, M. Schmelz1, HJ. Solinski1 Introduction Plastic changes in human DRG neurons shape the altered function of skin afferents in various diseases but are difficult to study due to limitations. While murine models show significant divergence from human DRG neuron-types, pigs offer a closer physiological and transcriptomic match. Pruriceptive-neurons are of particular interest in chronic itch conditions such as atopic dermatitis. IL-31, a key mediator of chronic itch and signals through IL31RA/OSMR, a receptor-complex present in a small subset of porcine DRG-neurons. Objectives To develop a functional method to identify pruriceptive neurons in pig DRG cultures, characterize their sensory properties, and assess whether IL-31 activates and/or sensitizes them, as in human chronic itch. Methods By calcium imaging, we identified pruriceptive-neurons with overlapping responses to capsaicin and histamine. Neuronal dynamics were assessed using low/high-frequency sine-wave and rectangular electrical-stimulation. Finally, we tested pruriceptive-neurons for IL-31-induced activation, in vitro and in vivo, and sensitization to pruritogens. Results We identified pig DRG neurons responsive to both capsaicin and histamine, consistent with a pruriceptive phenotype. These neurons showed silent nociceptor-like features: histaminergic sensitivity, poor frequency following, and prolonged calcium transients.IL-31 directly activated ~25% of pruriceptive neurons in vitro and intradermal injection of IL-31 elicited a neurogenic flare in pig, supporting direct activation of silent nociceptors by IL-31. IL-31 also sensitized neuronal responses to repeated histamine application. Conclusions Our study demonstrates that pruriceptive DRG-neurons in pig exhibit a functional silent nociceptor phenotype and respond to IL-31 with direct activation and facilitating chronic itch signalling. These findings provide a translationally relevant cellular model to study pruriceptive signalling, offering insight into chronic itch mechanisms in diseases like atopic dermatitis.
P84
Title:
Redox-dependent
activation of protein kinase G 1α (PKG1α) mediates acute itch
processing
Submitting
author:
Berg, Tim - Insitute of Pharmacology and Clinical
Pharmacy, Max-von-Laue-Str. 9, Goethe University Frankfurt am Main,
Germany
Abstract:
Tim Berg1, Jonas Petersen1, Phillip Eaton2, Achim Schmidtko1, Wiebke Kallenborn-Gerhardt1 1 Institute of Pharmacology and Clinical Pharmacy, Goethe University, 60438 Frankfurt am Main, Germany. 2 The William Harvey Research Institute, Charterhouse Square, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK. Introduction: Recent studies have shown that reactive oxygen species (ROS) exert specific signaling functions in sensory neurons. In particular, ROS can activate protein kinase G 1α (PKG1α) through oxidization of specific cysteine residues, leading to an enzymatically active dimeric state of PKG1α. While the role of redox-activated PKG1α in pain processing was intensively studied, its function in itch processing remains poorly understood. Objectives: In this study, we investigated the functional role of the redox-dependent activation of PKG1α in pruriceptive signaling. Methods: We used a global PKG1α knock-in (KI) mouse model, in which the oxidant-induced activation is prevented, while the cGMP-dependent activation remains intact. The itch behavior of PKG1α-KI and control mice was assessed after intradermal injection of various pruritogens. The expression of PKG1α in dorsal root ganglia (DRG) was analyzed using in situ hybridization and qRT-PCR experiments. Cultured DRG neurons were used for ROS-detection assays and calcium imaging experiments. Results: Our findings revealed an altered behavior of PKG1α-KI mice in models of pruritogen-induced acute itch. In situ stainings and RT-qPCR revealed a high co-expression of PKG1 with major itch sensors. Stimulation of DRG neurons with distinct pruritogens resulted in increased ROS levels and altered calcium influx in DRG neurons. Conclusion: These data suggest that the redox-dependent activation of PKG1α might be involved in pruriceptive signaling in sensory neurons.
P85
Title:
Exploring
the interventional effect and mechanism of oxymatrine on cholestatic
pruritus by relieving the primary and secondary aspects of pruritus
Submitting
author:
Dai, Wenzhang - College of Pharmacy, Jinan University,
Guangzhou , Guangdong, China
Abstract:
Wenzhang Dai, Junlin Wang, Hong Nie* College of Pharmacy, Jinan University, Guangzhou , China Introduction: Pruritus is one of the most common disabling symptoms in cholestatic patients, the effective treatment of cholestatic pruritus remains a challenge. Oxymatrine (OMT), the main active ingredient in the natural plant Sophorae Flavescentis Radix, has been shown to have an antipruritic effect, but its effect against cholestatic pruritus is unknown. Objectives: The etiology of cholestatic pruritus consists of two main aspects; the production of pruritogens after cholestasis is considered to be the primary aspect, and pruritogen-induced itch signaling is considered to be the secondary aspect. Therefore, the aim of this study was to clarify the dual regulatory effects of OMT in cholestatic pruritus. Methods: Calcium imaging was used to detect calcium ion influx in DRG primary neurons. ELISA were used to detect changes in hepatobiliary functional indices in cholestatic pruritic mice. Animal behavioral changes were used to assess itch. To investigate the mechanism of OMT in ameliorating cholestasis and alleviating pruritus by reducing pruritogens using a multi-omics technique. Results: Calcium imaging showed that the calcium ion influx in DRG neurons induced by deoxycholic acid was significantly inhibited after OMT pretreatment. The results of ELISA assay showed that the serum levels of AKP and TBA in cholestatic pruritic mice were significantly reduced after OMT intervention. Behavioral assessment showed that the number of scratching in cholestatic pruritus mice was significantly reduced after OMT intervention. In addition, the results of the multi-omics analysis indicated that OMT exerted an alleviating effect on cholestatic pruritus by regulating bile acid and cholesterol metabolism to decreasing the level of bile acids，which is the potential pruritogens, through up-regulating the expression of ABCG8, NTCP and FXR proteins. Conclusion: In this study, we demonstrated that OMT has a bidirectional regulation of antipruritic effects in cholestatic pruritus.
P86
Title:
Slack
potassium channels in spinal dorsal horn control itch and neuropathic
pain
Submitting
author:
Engel, Patrick - Institute of Pharmacology and Clinical
Pharmacy, Goethe University Frankfurt, Max-von-Laue Str. 9 60438
Frankfurt/MAin
Additional
Authors:
Fangyuan Zhou/ Institute of Pharmacology and Clinical
Pharmacy, Goethe University Frankfurt, Frankfurt am Main, Germany
Peter Ruth/ Department of Pharmacology, Toxicology and Clinical
Pharmacy, Institute of Pharmacy, University of Tuebingen, Tuebingen,
Germany Robert Lukowski/Department of Pharmacology, Toxicology and
Clinical Pharmacy, Institute of Pharmacy, University of Tuebingen,
Tuebingen, Germany Achim Schmidtko / Institute of Pharmacology and
Clinical Pharmacy, Goethe University Frankfurt, Frankfurt am Main,
Germany Ruirui Lu / Institute of Pharmacology and Clinical Pharmacy,
Goethe University Frankfurt, Frankfurt am Main, Germany
Abstract:
Introduction: The sodium-activated potassium channel Slack (KNa1.1, Kcnt1) plays a critical role in tuning neuronal excitability. Previous studies have revealed that Slack is expressed in neurons of the superficial dorsal horn of the spinal cord. However, the cellular distribution and role of Slack in spinal dorsal horn neurons remains poorly understood. Objectives: In this study, we investigated the cellular distribution of Slack in the dorsal horn of the spinal cord and assessed the functions of Slack in dorsal horn neurons to the processing of itch and pain. Methods: We used in situ hybridization and immunohistochemistry to characterize the distribution of Slack in the spinal cord. We generated mice in which Slack is conditionally ablated in spinal dorsal horn neurons (Lbx1-Slack-/- mice). The behavior of Lbx1-Slack-/- and control mice was analyzed in models of itch and pain. Results: We found that Slack is predominantly expressed in excitatory interneurons of the spinal dorsal horn and coexpressed with neuromedin B receptors. Lbx1-Slack-/- mice demonstrated significantly increased scratching after intradermal injection of chloroquine, LY344864, and histamine, and after intrathecal delivery of neuromedin B. Furthermore, Lbx1-Slack-/- mice showed increased neuropathic pain behavior in the spared nerve injury model but normal responses in an inflammatory pain model. Conclusion: Our study provides in vivo evidence that Slack expressed in spinal dorsal horn neurons inhibits acute itch induced by various pruritogens and neuropathic pain after peripheral nerve injury.
P87
Title:
IL-4
from basophils mediates itch in abrasion wounds: a potential
therapeutic effect of topical PDE4 inhibitors
Submitting
author:
Hashimoto, Takashi - National Defense Medical College,
Department of Dermatology, 3-2, Namiki, Tokorozawa, 359-8513 Saitama,
Japan
Abstract:
Abrasion wounds often become itchy during the re-epithelization/wound healing process. Managing itch in such wounds is important, as the scratching can impede proper wound healing. However, effective management remains challenging due to the limited understanding of the underlying pathophysiology. In this study, we aimed to identify the pruritogens involved in abrasion wound-associated itch and to explore a potential therapeutic approach. Abrasion wounds (epidermal abrasion with a thin epidermal layer remaining) were induced on the dorsal skin of mice on day 0 via tape stripping and brushing. Erosions were evident from day 0 to day 2. By day 4, the wound surface was covered with crusts, and complete re-epithelization was observed on day 10. Scratching behavior was observed from day 1 to day 9, peaking on day 4. On day 4, a marked increase in the expression of IL-4 and Mcpt8 (a basophil-specific protease) mRNA was detected at the wound sites, whereas IL-31 expression showed no significant change. Immunofluorescence staining further confirmed the presence of IL-4–expressing basophils at the lesions. The topical administration of an IL-4 neutralizing antibody significantly reduced scratching behavior on day 4. Similarly, topical application of crisaborole, a PDE4 inhibitor known to suppress the IL-4 production from basophils, attenuated lesional IL-4 expression and scratching behavior. These findings suggest that IL-4 derived from basophils contributes to the development of itch in abrasion wounds and that topical PDE4 inhibitors such as crisaborole may represent an effective therapeutic option.
P88
Title:
Strain
and sex differences in itch threshold in mice
Submitting
author:
Hashimoto, Nagisa - Nara Women's University,
Environmental Health, Kitauoya-Higashimachi, Nara, 630-8506, Japan
Additional
Authors:
Nagisa Hashimoto 1), Midori Hashino 1), Tsuyoshi Koide
2), Keiko Takanami 1)2) 1) Environmental Health, Faculty Human Life
and Environmental Sciences, Nara Women's University, Nara, Japan 2)
Mouse Genomics Resource Laboratory, National Institute of Genetics,
Mishima, Japan
Abstract:
With the advancement of genetic modification technologies, C57BL/6 (B6) mouse strain are now widely used in basic research including itch. However, B6 mice do not necessarily represent a model that directly reflects human itch. To understand individual differences in human itch sensitivity, we analyzed the itch sensitivity among strains of mice using wild derived strain MSM that retains unique behaviors observed in the wild, Japanese fancy strain JF1, in addition to laboratory strain B6. In this study, we analyzed three types of itch: spontaneous itch as an indicator of endogenous itch, alloknesis as mechanical itch, and histamine-evoked itch as chemical itch. Spontaneous itch and saline(control)-induced itch were hardly observed in all three strains, suggesting that there is little endogenous itch in any of the strains. Mechanical itch-related behavior increased in JF1 compared with B6. However, B6 showed a heightened aversive behavior toward the filaments. At a low concentration of histamine, the JF1 strain exhibited more scratching behavior. At a high concentration, both the JF1 and MSM strains showed increased scratching behavior relative to B6 and females exhibited more scratching behavior than males in the JF1 strain. In the present study, significant differences in chemical itch thresholds were observed among mouse strains, and there was a suggested tendency for a correlation between sensitivity to mechanical and chemical itch across strains. These findings indicate that using mouse strains other than the commonly used experimental strains may also lead to the development of animal models for itch research.
P89
Title:
Honeybee
Venom Vitellogenin Triggers Sensory Nerve Excitation Leading to Itch
Submitting
author:
Jurcakova, Danica - Comenius University in Bratislava,
Jessenius Faculty of Medicine in Martin, Department of Pathological
Physiology, Mala Hora 4, 036 01 Martin, Slovakia
Additional
Authors:
Michal Pokusa / Comenius University in Bratislava,
Jessenius Faculty of Medicine in Martin, Department of Pathological
Physiology, Slovak Republic Renata Pecova / Comenius University in
Bratislava, Jessenius Faculty of Medicine in Martin, Department of
Pathological Physiology, Slovak Republic Dalibor Kodrik / Institute
of Entomology, Biology Centre, Czech Academy of Science, Czech
Republic & Faculty of Science, University of South Bohemia, Czech
Republic
Abstract:
Introduction: Honeybee (Apis mellifera) venom is a complex mixture of bioactive molecules that provokes local inflammatory responses, including redness, swelling, pain, and itch. While the nociceptive aspects of venom have been characterized, the mechanisms underlying itch remain poorly understood. We hypothesized that vitellogenin (Vg), a yolk glycoprotein surprisingly also present in honeybee venom and known to have allergenic potential, may contribute to this pruritic response. Objectives: This study aimed to determine whether vitellogenin can directly activate sensory neurons and induce itch-related behavior, thereby implicating it as a pruritogenic component of honeybee venom. Methods: C57BL/6 mice were used for calcium imaging of dissociated dorsal root ganglia (DRG) neurons to assess vitellogenin activation. Additionally, extracellular single-unit recordings from ex vivo innervated mouse skin quantified responses (action potential number, frequency). Behavioral assays with intradermal cheek injections distinguished scratching (itch) from wiping (pain). Results: Vitellogenin activated 20 of 99 DRG neurons. Importantly, 90% of these Vg-responsive neurons also responded to chloroquine, and 70% to capsaicin, indicating activation of both pruriceptive and nociceptive pathways. In ex vivo skin–nerve recordings, Vg robustly activated chloroquine-sensitive C-fibers (49 ± 7 APs; 6.3 ± 0.9 Hz, n=8), while chloroquine-insensitive fibers showed minimal activation (1.1±0.2 Aps; 0.4±0.1 Hz; n=8). The effective concentration 50% (EC50) for Vg was 0.42 µg/ml (2.1 nM). In vivo, Vg induced significant scratching (40 ± 4 bouts vs. 9 ± 1.3 in controls; p = 0.018) without increasing wiping behavior. Moreover, honeybee venom and its component melittin similarly triggered robust scratching (161±15 bouts, n=8, p=0.008; 86±12 bouts, n=8, p=0.04, respectively). Conclusion: Vitellogenin selectively activates pruriceptive nerve fibers and induces itch-related behavior in mice. These findings identify Vg, alongside melittin, as honeybee venom components that contribute to pruritus. This work was supported by VEGA grant No. 1/0065/23 and Czech Science Foundation grant No. 24-10662S.
P90
Title:
Human
semaphorin 3A expression is suppressed by skin barrier defects, not
by cytokines
Submitting
author:
Kamata, Yayoi - Juntendo Itch Research Center (JIRC),
Institute for Environmental and Gender-Specific Medicine, Juntendo
University Graduate School of Medicine, 2-1-1 Tomioka, Urayasu,
Chiba, Japan
Abstract:
Yayoi Kamata1, Nanami Tanemoto1, Takahide Kaneko2, Yasushi Suga2, Mitsutoshi Tominaga1, Kenji Takamori1,2 1Juntendo Itch Research Center (JIRC), Institute for Environmental and Gender-Specific Medicine, Juntendo University Graduate School of Medicine, Chiba, Japan 2Department of Dermatology, Juntendo University Urayasu Hospital, Chiba, Japan Introduction Epidermal nerve fiber density is elevated in skin with barrier disrupted skin, such as atopic dermatitis (AD) and dry skin, than in normal skin. It is mainly attributed to an imbalance between the expression of nerve elongation factor (e.g. nerve growth factor) and nerve repulsion factor (e.g. semaphorin 3A [Sema3A] and KAL-1) in keratinocytes. Actually, Sema3A levels are reduced in the lesional skin of AD patients. However, the mechanisms suppressing Sema3A expression in lesional skin of AD have remain unclear. Objective This study aimed to elucidate the mechanisms that reduce Sema3A expression in AD using keratinocyte models that mimic AD and models of epidermal barrier disruption. Methods Experiment 1. Normal human epidermal keratinocytes (NHEKs) were incubated with cytokines associated with AD pathology and analyzed by real-time PCR. Experiment 2. NHEKs were transfected with human filaggrin (FLG) siRNA and incubated with or without a mixture of AD-related cytokines (IL-4, IL-13, IL-22 and TNF-α). Gene expression was then analyzed by real-time PCR. Experiment 3. 0.2% Triton X-100 solution was applied to the stratum corneum surface of reconstructed human epidermis (RHE). After 15 min, RHE samples were washed, and total RNA was extracted at various time points and analyzed by real-time PCR. Results Sema3A expression was increased by IL-4, IL-13, and TNF-α. The combination of IL-4, IL-13, IL-22, and TNF-α significantly decreased FLG mRNA expression in NHEKs, but increased the expression of Sema3A and KAL-1 mRNA. Although FLG silencing suppressed Sema3A expression in NHEKs, the cytokine-induced increase in Sema3A was attenuated by FLG knockdown. Sema3A expression was reduced in RHE following barrier disruption
P91
Title:
IL-4 and
IL-13 are not involved in IL-31-induced scratching behaviours, but
they are involved in IL-31-induced mechanical alloknesis in mice
Submitting
author:
Kawai, Rana - Department ofDermatology, Dokkyo Medical
UniversitySaitama Medical Center, 2-1-50,Minamikoshigaya, Koshigaya,
Saitama343-8555, Japan
Abstract:
Introduction: Both IL-4/IL-13 and IL-31 play a crucial role in pruritus associated with various pruritic skin diseases. However, the interplay between these interleukins in pruritus remains unclear. We have previously reported that IL-4/IL-13 is involved in alloknesis in mouse dry skin model (Ichimasu N et al, Exp Dermatol 2021). Objectives: This study aimed to investigate the role of IL-4 and IL-13 in scratching behaviours and mechanical alloknesis induced by IL-31 in mice. Methods: Scratching behaviours were analyzed using a real-time scratch counting system after the intradermal administration of IL-31, either with or without pre-administration of IL-4/IL-13. Similarly, mechanical alloknesis induced by von Frey filaments was evaluated by manually counting scratch bouts. Results: We determined the minimum dose of IL-31 required to induce itch-related scratching behavior. The amount of IL-31, the co-administration of IL-4/IL-13, pre-administration of IL-4/IL-13 for 30 minutes, the intradermal administration of IL-4, and the intravenous pre-administration of IL-4 did not affect IL-31-induced itch-associated scratching behaviour. Neutralising antibodies against IL-4 and IL-13, when pre-administered, did not affect IL-31-induced itch-associated scratching behaviour. Mechanical alloknesis was induced by IL-31. The pre- and simultaneous administration of IL-4/IL-13 did not have an additional effect on the mechanical alloknesis induced by IL-31. Conversely, pre-administration of neutralizing antibodies against IL-4/IL-13 inhibited the mechanical alloknesis induced by IL-31. Conclusion: IL-31 is able to induce itch, as demonstrated by scratching behaviours and mechanical alloknesis. IL-4/IL-13 supports IL-31-induced mechanical alloknesis, but not scratching behaviours. The differential effects of IL-4 and IL-13 on the two types of pruritus related to IL-31 may help to clarify the complicated clinical situations experienced when using dupilumab and nemolizumab.
P92
Title:
Regulatory
mechanism of mechanical alloknesis via the endomorphin-CD26/DPPIV
enzyme axis
Submitting
author:
Komiya, Eriko - Juntendo Itch Research Center (JIRC),
Institute for Environmental and Gender Specific Medicine, Juntendo
University Graduate School of Medicine, 2-1-1 Tomioka, Urayasu-city,
Chiba 279-0021, Japan
Abstract:
Eriko Komiya1)2) Mitsutoshi Tominaga1), Kotaro Honda1), Sumika Toyama1), Yayoi Kamata1), Makino Watanabe2), Akira Minami2), Kenji Takamori1),3) 1) Juntendo Itch Research Center (JIRC), Institute for Environmental and Gender Specific Medicine, Juntendo University Graduate School of Medicine, Chiba, Japan 2) Department of Functional Morphology, Faculty of Pharmacy, Juntendo University, Chiba, Japan 3) Department of Dermatology, Juntendo University Urayasu Hospital, Chiba, Japan Introduction: Mechanical alloknesis refers to itch hypersensitivity induced by normally innocuous mechanical stimuli and is commonly observed in patients with dry skin conditions, such as atopic dermatitis and xerosis. We previously identified CD26/dipeptidyl peptidase IV (DPPIV) as a key regulator of psoriatic itch. Objectives: This study aimed to elucidate the molecular mechanism underlying mechanical alloknesis, focusing on the role of CD26/DPPIV and its interaction with endomorphins (EM-1 and EM-2), endogenous mu-opioid receptor ligands. Methods: Mechanical alloknesis was assessed in CD26/DPPIV knockout (KO) and wild-type (WT) mice by counting scratching responses following innocuous mechanical stimulation (von Frey filaments) on the rostral back. Immunohistochemical and behavioral pharmacological analyses were used to evaluate the expression and function of CD26/DPPIV and EMs. Recombinant CD26/DPPIV, mutant enzyme lacking activity, and naloxone methiodide (a peripheral mu-opioid receptor antagonist) were intradermally administered. Fiber-type specificity was investigated using QX-314–mediated functional silencing. Results: CD26/DPPIVKO mice exhibited significantly elevated mechanical alloknesis compared with WT controls, while spontaneous scratching was unchanged. The alloknesis score was reduced by recombinant CD26/DPPIV or naloxone methiodide, but not by the enzymatically inactive mutant. Both EM-1 and EM-2 induced alloknesis, whereas their DPPIV-digested forms did not. Immunohistochemistry revealed EM localization in keratinocytes, fibroblasts, Aβ-fibers (NF200/TrkB), pept
P93
Title:
Mrgprb2-mediated
mast cell activity is associated with increased skin fibrosis in a
BLM-model of systemic sclerosis
Submitting
author:
Kothari, Ruchita - Johns Hopkins School of Medicine,
Department of Neuroscience, 725 N Wolfe St, Baltimore MD, USA
Additional
Authors:
Daniel Capuzzi/Johns Hopkins School of Medicine,
Xinzhong Dong/Johns Hopkins School of Medicine
Abstract:
The development of pathogenic skin fibrosis in systemic sclerosis (SSc) is well established, but the early mechanisms which trigger these fibrotic changes remain unclear. Specifically, mast cells have been known to infiltrate human SSc lesional skin in early stages, peaking during stages of collagen deposition, and dissipating in regressing lesions. Similarly, mouse models of bleomycin (BLM)-induced skin fibrosis present with early infiltration of mast cells that reduce as the disease progresses. Despite the association of mast cells in early stage SSc, their role in initiating fibrotic changes and pruritus in early-stage disease remains debated, often due to conflicting data in non-specific mast cell depletion models. Given the role of Mrgprb2 in mediating inflammation via cytokines and proteases distinct from canonical IgE signaling, we hypothesized that this receptor influences the role of mast cell-mediated fibrosis in SSc. Here, we show that mast cells via Mrgprb2 play a role in skin fibrosis in the BLM model of skin fibrosis. Mast cells accumulate in the skin of BLM-treated wildtype (WT) but not Mrgprb2-/- mice. Additionally, Mrgprb2-/- mice exhibit attenuated disease severity in the skin measured by reduced collagen deposition, and decreased expression of matrix metalloproteinases and inflammatory markers associated with fibrosis. Antihistamines are not always effective in SSc-associated itch, and we further hypothesized that Mrpgrb2-mediated non-histaminergic itch may play a role. We observe an increase in pruritus after BLM injections, but this increase is not Mrgprb2-dependent. Nonetheless, this is the first report investigating itch in the BLM model of skin fibrosis, further correlating this model to clinical SSc. These findings implicate the role of Mrgprb2-mediated mast cell activity in potentiating fibrosis in SSc. Further investigation is necessary to understand the pruritic mechanisms in BLM-induced skin fibrosis.
P94
Title:
IgE
urticaria
Submitting
author:
Kothiwala, Raj Kumar - JLN Medical College Ajmer
Additional
Authors:
Dr Kriti Jain
Abstract:
IgE urticaria is type 1st Hypersensitivity mediated stimulated by various triggers ie infections ,foods & medicines and other similar substances . it's very very distracting to sleep and normal life.when it occurs it may last months to years . generally redness occurs after itching and redness is liliac in colour as of LE. Atopics are offended by IgE urticaria.As part of work up Blood counts , Sugar, thyroid ,CRP & Serum IgE are minimum investigations Required for management of IgE urticaria . Treatment modalities same other than Cyclosporine and Biologicals
P95
Title:
Itch
sensitization induced by ciguatoxins: behavioral and functional
studies
Submitting
author:
Le Garrec, Raphaele - Laboratoire Interactions
Epitheliums-Neurones, Univ Brest, F-29200 Brest, France
Additional
Authors:
Raphaele LE GARREC 1, Babina SANJEL 1, Taylor
FOLLANSBEE 2, Mirela IODI CARSTENS 2, Laurent MISERY 1, Earl CARSTENS
2 1 Laboratoire Interactions Epitheliums-Neurones, Univ Brest,
F-29200 Brest, France. 2 Department of Neurobiology, Physiology and
Behavior, University of California, Davis, California, United States.
Abstract:
Introduction Itch can become chronic by mechanisms of sensitization of its peripheral and/or central neural pathways. Two manifestations of itch sensitization are hyperknesis, where pruritus induced by an itchy stimulus is exacerbated, and alloknesis, where a normally non-itchy stimulus triggers itch. Ciguatoxins (CTXs) are the neurotoxins responsible for ciguatera poisoning, the most frequent symptoms of which are sensory neuropathic disorders, including an intense and persistent itch. Our previous behavioral data in mice showed that intradermal CTX induces a generalized itch and intermittent freezing suggesting an involvement of the central nervous system. Objectives Our study aimed to test the hypothesis that CTXs induce itch sensitization. Methods Mechanical alloknesis was studied in mice after intradermal injection of CTX at nanomolar concentrations in the nape. From thirty minutes to eight days after injection, ten stimulations with a 0.07 g von Frey filament were applied in the area surrounding the injection site. The alloknesis score at each time was the sum of scratching responses triggered by stimulations. Hyperknesis was studied both behaviorally and functionally in vitro. In mice and dorsal root ganglion neurons, we studied the ability of a pretreatment with CTX to potentiate scratching behaviors and calcium responses induced by pruritogens including histamine and chloroquine. Results In mice, intradermal CTX pretreatment was able to potentiate the scratching or freezing behaviors induced by certain but not all the pruritogens studied, and to make itchy a normally non-itchy mechanical stimulus. In vitro, CTX pretreatment potentiated the calcium response of pruriceptors to certain but not all pruritogens. Conclusion Our results indicate that CTX is capable of inducing hyperknesis and alloknesis by sensitizing specific itch pathways, at least in part by an action exerted at the peripheral level. The identification of the itch pathways sensitized by CTX will help to elucidate mechanisms underlying long-lasting itch of ciguatera.
P96
Title:
Drug
metabolites drive chronic kidney disease-associated pruritus
Submitting
author:
Li, Fengxian - Department of Anesthesiology
Zhujiang Hospital, Southern Medical University
253 Gongye Road, Guangzhouu, China
Abstract:
Chronic kidney disease-associated pruritus (CKD-aP) is a deliberating condition affecting over 50% of CKD patients. Although current treatments, including kappa-opioid agonists (e.g., nalfurafine), provide some relief, their efficacy remains suboptimal. Given CKD’s chronic nature and its complex metabolic dysregulation, we therefore conducted a cross-sectional study at the hemodialysis center and enrolled 109 patients who had been diagnosed with CKD and had been on regular dialysis for more than three months. Patients were categorized as pruritic or non-pruritic based on their WI-NRS score. Serum samples were collected to investigate metabolic pathways underlying pruritus and identify key mediators of chronic itching. Intriguingly, differentially altered metabolites were primarily linked to neuroinflammatory and neurometabolic pathways, in association to exogenous drug metabolism. Notably, most of these metabolites were uremic retention solutes, strongly correlated with CKD progression. KEGG enrichment analysis of metabolites identified arginine biosynthesis and purine metabolism pathways, which are involved in the regulation of synaptic plasticity and neurodegenerative pathologies. Our results suggest that CKD-aP is associated with the accumulation of metabolites, some of which cause pruritic responses by acting on peripheral and central nerves.
P97
Title:
Keratinocytes
and TNF increase human iPSC-derived sensory neuron chemosensitivity
in a druggable model for atopic itch
Submitting
author:
Mießner, Hendrik - University of Cambridge, Department
of Pharmacology, Cambridge, UK; Beiersdorf AG, Research &
Development, Hamburg, Germany
Additional
Authors:
Benjamin Al (Beiersdorf AG, Research & Development,
Hamburg, Germany) Hendrik Reuter (Beiersdorf AG, Research &
Development, Hamburg, Germany) Judith Anna Seidel (Beiersdorf AG,
Research & Development, Hamburg, Germany) Ewan St. John Smith
(University of Cambridge, Department of Pharmacology, Cambridge, UK)
Abstract:
Introduction Atopic dermatitis (AD) is a highly prevalent, relapse-remitting, inflammatory skin disease, the hallmark symptom being chronic itch. Mechanisms underlying AD itch are multifactorial, involving various cells, receptors, and mediators. However, many in vitro itch model systems focus solely on sensory neurons. Objective Developing a physiologically relevant, humanized model system for AD itch research and drug development is crucial. Methods Human induced pluripotent stem cell-derived sensory neurons (iPSCSNs) were cultured with human primary skin cells to form deconstructed skin models. Main functionality was achieved using a model with direct cell contact, in a 2.5D co-culturing format, which mimics natural skin innervation and permits both paracrine exchange and juxtacrine signaling. Results iPSCSNs exhibited functional and exploitable TRPA1 responses in direct contact cultures not seen in monotypic cultures or iPSCSNs conditioned with keratinocyte medium. Different AD-associated cytokines were used to stimulate the co-culture systems to mimic an inflamed lesional skin environment, which was found to further increase cell chemosensitivity. Finally, TRPA1 and JAK1/2 inhibition reduced iPSCSN responses to pruritogens (TSLP, IL31), thus highlighting TRPA1 as a therapeutic target for AD itch. Conclusion This study demonstrates that human deconstructed skin models can be a useful tool in AD and broader pruritus research.
P99
Title:
Dynamics
of inhibitory neurons in the dorsal horn of the spinal cord in
pruritic mouse models
Submitting
author:
Morita, Motoki - Juntendo Itch Research Center (JIRC),
Institute for Environmental and Gender-Specific Medicine, Juntendo
University Graduate School of Medicine, Chiba, Japan
Abstract:
Motoki Morita1, Mitsutoshi Tominaga1,Miho Shiratori-Hayashi1,2, Eriko Komiya1,3, Kenji Takamori1,4 1 Juntendo Itch Research Center (JIRC), Institute for Environmental and Gender-Specific Medicine, Juntendo University Graduate School of Medicine, Chiba, Japan 2 Department of Molecular and Systems Pharmacology, Faculty of Pharmacy, Juntendo University, Chiba, Japan 3 Department of Functional Morphology, Faculty of Pharmacy, Juntendo University, Chiba, Japan 4 Department of Dermatology, Juntendo University Urayasu Hospital, Chiba, Japan Background: Sensory signals from the periphery are modulated by excitatory and inhibitory neurons in the spinal cord. Previous studies (e.g., Chen et al., Nat Commun 2020) have shown that dysfunction of inhibitory neurons in the spinal cord exacerbates itch in the dry skin model. However, it remains unclear whether this phenomenon is specific to dry skin or reflects a common mechanism across other chronic itch models. Therefore, we focused on classifying dorsal horn neurons into inhibitory and excitatory types and analyzed their activation in three itch models: dry skin model, psoriasis model, and atopic dermatitis (AD) model. Objectives: To determine whether inhibitory and excitatory neuron activity differs across chronic itch models. Methods: Scratching behavior was quantified using the SCRABA-Next system. Inhibitory and excitatory neuron populations, along with Fos-positive (activation marker) cells in the cervical dorsal horn, were analyzed via RNAscope in situ hybridization in three itch models. Results: While the expression patterns of inhibitory, excitatory, and Fos-positive neurons varied among the models, all chronic itch models showed co-activation of both neuronal types. AD mice exhibited a significant reduction in inhibitory neuronal markers compared to controls, whereas no such reduction was observed in other models. Conclusion: Although chronic itch consistently involves both inhibitory and excitatory pathways, model-specific differences in their balance may be critical for elucidating the underlying mechanisms.
P100
Title:
Gene
Expression Profiling of Eccrine Sweat Glands Reveals Pruritus-Related
Pathways in Acquired Idiopathic Generalized Anhidrosis
Submitting
author:
Murota, Hiroyuki - Nagasaki University, Department of
Dermatology, 1-7-1, Sakamoto, Nagasaki, Japan
Abstract:
Background: Sweating is a vital physiological function for maintaining homeostasis, and its impairment can lead to significant health disturbances. In anhidrosis, patients often experience elevated skin temperature and severe pruritus accompanied by pain. Acquired idiopathic generalized anhidrosis (AIGA) is a rare and intractable disorder of unknown etiology that presents with these symptoms. Disruption of the eccrine sweat gland microenvironment has been implicated in its pathogenesis. Objective: To elucidate the mechanisms of painful pruritus in AIGA, we investigated transcriptional differences between sweating and non-sweating eccrine sweat glands. Methods: Eccrine sweat glands were isolated from sweating (n=4) and non-sweating (n=3) skin regions of AIGA patients. RNA sequencing was performed, and genes showing a ≥2-fold differential expression with statistical significance (p < 0.01) were identified. Results: Transcriptomic analysis revealed upregulation of IL-18, skin barrier-associated serine protease inhibitors (e.g., SPINK6), neuroregulatory molecules (e.g., prokineticin 2), and HLA class II immune-related genes in non-sweating glands. These results suggest that enhanced inflammation, barrier dysfunction, and sensory sensitization may synergistically contribute to the persistence and amplification of pruritus in AIGA. Conclusion: Pruritus in AIGA appears to be associated not with increased expression of itch-inducing molecules per se, but rather with a gene expression pattern that lowers the itch threshold and enhances sensory sensitivity under chronic inflammatory conditions.
P101
Title:
Altered
resting-state anterior insula connectivity is associated with
vigorous scratching in atopic dermatitis
Submitting
author:
Ng, Xin Yi - Xin Yi NG1,2, Salahah AHMED2, Piers ALLEN2,
Ines ARGOUB2, Ullrich BARTSCH3, Conor BRODERICK2, Shona CAMERON2,
Paola DAZZAN4, Jesper ELBERLING5, Paul GRINGRAS6, Desaline JOSEPH6,
Wioleta KOWALSKA6, Ruchika KUMARI2, Nicole MARIANI4, Connor MCKAY6,
Carmine P
Abstract:
Itch is a prominent hallmark of atopic dermatitis (AD) and can significantly impact quality of life. Traditionally, itch is quantified by self-reported questionnaires such as the peak pruritus numerical rating scale. Recent developments in wearables have enabled recording of high-frequency movement to objectively quantify scratching behaviour. Neuroimaging studies have identified alterations in brain activation patterns in AD patients during itch induction and scratching. However, functional connectivity between brain regions involved in itch, scratch, and associated cognitive-emotional processes under real-world conditions remains poorly understood. This study aims to understand the relationship between itch-scratch burden and resting-state functional connectivity in AD adolescent patients and healthy controls. Ten adolescents with AD and seven healthy controls were recruited. Participants wore an actigraphy watch on their non-dominant wrist for 2-12 consecutive nights. Video recordings were used to manually label scratch events and train a fully connected neural network model to predict scratch episodes on remaining nights. From the predicted dataset, scratch parameters such as average movement frequency per scratch episode and total scratch duration were calculated for each subject. Resting-state fMRI scans were acquired and seed-to-whole brain correlation analyses were performed with anterior and posterior insula as seeds. z-transformed correlation coefficients extracted from different ROIs were then correlated with scratch parameters. AD patients exhibited higher total scratch duration and average movement frequency per episode. Anterior insula (aInsula) connectivity to the anterior cingulate cortex (ACC) positively correlated with average movement frequency (r=0.69, p=0.0059) but not total scratch duration. Increased aInsula-ACC connectivity may reflect a stronger urge to scratch, contributing to more vigorous scratching. These preliminary findings propose aInsula as a future target for neurofeedback interventions to regulate scratching behaviour in AD.
P102
Title:
Cellular
and molecular basis of pruritus in keloid scars
Submitting
author:
Ngwenya, Takunda - Kings College London, Wolfson Sensory
Pain & Regeneration Center and Center for Inflammation Biology
and Cancer Immunology
Abstract:
Introduction and Aim
Keloids are a type of scar characterized by abnormal collagen deposition and expansion beyond the wound boundary. Besides the unwanted aesthetics, keloids can also produce severe pruritus, leading to patients experiencing decreased health-related quality of life. Unfortunately, a lack of research means the source of this sensation is unknown. Therefore, this study aims to explore itch specific targets for therapeutic purposes.
Methods
People living with keloids were asked to complete a questionnaire regarding their keloid itch status. A list of putative itch mediators was assembled using a literature search. Using three published single cell RNA-sequencing datasets of keloid scars, the expression of itch mediators will be explored and cell subset sources ascertained. The future work will include growing the specific cell populations that differentially express the identified itch genes and explore the interference with the nervous system.
Results
Survey results (n=96) highlighted that itch is prevalent across the keloid population and can be moderate to severe in severity. Standard intralesional steroid injections lead to no improvement or worsening of symptoms in the majority of cases. These results highlighted the need to address the specific source(s) of keloid itch in order to develop targeted treatments. Next steps will be to analyze three published single cell RNA-sequencing datasets of keloid scars, and cross-reference cell subset expression with a list of literature-sourced putative itch mediators to identify potential sources of keloid-specific itch.
Conclusions
We have confirmed that itch is a significant issue for people living with keloids. Next steps will be to identify cells expressing putative itch mediators by single cell RNA-sequencing. This will be followed by validation studies using ex vivo labelling of the identified molecular targets in keloid tissue samples.
P104
Title:
Loss of
keratinocyte autophagy amplifies pruritus via barrier dysfunction and
nerve sensitization in atopic dermatitis
Submitting
author:
Peng, Ge - Juntendo University Graduate School of
Medicine, Atopy (Allergy) Research Center, Tokyo, Japan
Abstract:
Introduction: Itch is a hallmark symptom of atopic dermatitis (AD), significantly impairing patients’ quality of life. While immune dysregulation and barrier dysfunction are well-established contributors to AD-associated pruritus, the role of keratinocyte-intrinsic processes such as autophagy remains unclear. Autophagy maintains cellular homeostasis by removing damaged organelles and modulating inflammation. Recent evidence suggests impaired autophagy in AD, but its relevance to itch is not fully understood. Objective: To investigate how keratinocyte autophagy deficiency influences the development of AD and modulates itch-related pathways. Methods: Autophagy was suppressed in human keratinocytes using an adenovirus expressing a mutated ATG3 gene. AD-like skin inflammation was induced in keratinocyte-specific autophagy knockout mice via topical MC903 application. Epidermal barrier integrity, pruritus-related gene expression, skin innervation, immune cell infiltration, microbiome composition, and scratching behavior were also assessed. Results: Autophagy-deficient keratinocytes exhibited decreased expression of skin barrier-related proteins and upregulation of itch-associated molecules. Mice lacking keratinocyte autophagy showed increased transepidermal water loss, heightened epidermal nerve density, and significantly elevated scratching, even without inflammation. Upon AD induction, autophagy-deficient mice displayed exacerbated itch, increased CD4+ T cell infiltration, and skin dysbiosis characterized by Staphylococcus aureus overgrowth. Treatment with the autophagy-activating antimicrobial peptide human β-defensin-3 reduced itch and inflammation in wild-type AD mice but was ineffective in autophagy-deficient AD mice. Conclusions: Keratinocyte autophagy is critical for regulating itch in AD by maintaining barrier integrity, limiting nerve sensitization, and shaping the cutaneous immune and microbial environment. These findings highlight autophagy as a potential therapeutic target for alleviating itch in AD.
P105
Title:
CXCL10/CXCR3
AXIS AND MAST CELL INVOLVEMENT IN PAIN AND ITCH OF CUTANEOUS
NEUROFIBROMAS
Submitting
author:
Pham, Quoc Thao Trang - International Ph.D. Program in
Cell Therapy and Regenerative Medicine College of Medicine, Taipei
Medical University
Additional
Authors:
International Ph.D. Program in Cell Therapy and
Regenerative Medicine, College of Medicine, Taipei Medical
University, Taiwan
Abstract:
Introduction Pain and itch are common but underrecognized symptoms in cutaneous neurofibromas (cNFs), significantly affecting patients with neurofibromatosis type 1 (NF1). Emerging evidence implicates the CXCL10/CXCR3 chemokine axis in both sensory modulation and tumor biology, but its role in symptomatic cNFs remains unexplored. Objectives This study investigates the expression and potential sensory contribution of the CXCL10/CXCR3 axis in cNF-associated pain and itch. Methods We analyzed 53 surgically excised solitary cNFs using immunohistochemical staining for CXCL10, CXCR3, and immune cell markers. Patient-reported symptom severity was quantified using validated Chinese versions of the Short-form McGill Pain Questionnaire and the Eppendorf Itch Questionnaire. Results CXCL10 and CXCR3 were upregulated in both tumor and dermal compartments of symptomatic cNFs. A significantly higher proportion of mast cells expressed CXCL10 in symptomatic compared to asymptomatic tumors (51.18% vs. 19.07%, p < 0.0001), while CXCR3 expression on mast cells was not significantly different. Additionally, intraepidermal nerve fiber density was elevated in symptomatic lesions (p = 0.009), supporting a link between chemokine signaling and peripheral sensitization. Conclusion Our findings suggest that mast cell-derived CXCL10 may contribute to neuro-immune interactions underlying sensory symptoms in cNFs, independent of CXCR3 co-expression. This highlights the CXCL10 axis as a candidate mechanism driving pain and itch in these tumors and a potential therapeutic target.
P106
Title:
Ligand
based AHR activation in skin inflammation and neurocutaneous
crosstalk
Submitting
author:
Renkert, Hannah - University Hospital Münster, Section
for Pruritus Medicine, Department of Dermatology and Center for
Chronic Pruritus, Münster, Germany
Additional
Authors:
H.Renkert, E.Teitge, S.Ständer, K.Agelopoulos,
H.Wiegmann
Abstract:
Introduction The aryl hydrocarbon receptor (AHR) is a cytosolic, ligand-dependent transcription factor that plays a pivotal role in mediating cellular responses to xenobiotics. AHR is increasingly recognized as a central regulator of skin physiology, including epidermal barrier integrity, keratinocyte differentiation, and immunomodulatory processes. Objectives To elucidate AHR's contribution to cutaneous inflammation and neurocutaneous communication. Methods Primary human keratinocytes were exposed in vitro to AHR ligands including compounds from plant extracts with known AHR activity, as well as the prototypical proinflammatory ligand benzo[a]pyrene. Following ligand exposure, keratinocyte behavior was evaluated using standardized wound healing assays to assess changes in cellular proliferation and motility. Transcriptional changes in genes associated with inflammatory signaling and pruritus including IL-4, IL-13, IL-31 and their receptors, Cyp1a1 and markers affecting neuronal growth such as Sema3a and NGF were analysed by RT-qPCR. To investigate the functional consequences of AHR activation in a neurocutaneous context, keratinocytes were co-cultured with F11 neuronal cells and exposed to the AHR ligands. This co-culture system allowed for the assessment of intercellular communication and ligand-dependent modulation of neuroepidermal signaling. Results Our results demonstrated that AHR ligands significantly influenced keratinocyte gene expression profiles, particularly those related to inflammation, itch mediators, and epidermal-neuronal interaction. Furthermore, ligand treatment altered the nature of cell-cell communication between keratinocytes and F11 cells, indicating a modulatory effect of AHR signaling on neurocutaneous cross talk. Conclusion Collectively, these findings highlight the integral role of AHR in coordinating inflammatory responses and epidermal-neuronal interaction, reinforcing its relevance in the pathophysiology of inflammatory skin disorders and pruritic conditions.
P108
Title:
Neuromodulation
of Chronic Itch
Submitting
author:
Sbei, Sami - Washington University School of Medicine in
St. Louis, Department of Anesthesiology, 4940 Parkview Place, St.
Louis, MO 63110, USA
Abstract:
Introduction and objective: Chronic pruritus lasting longer than 6 weeks is estimated to affect 22% of the general population. Chronic pruritus can be triggered by nerve damage, drugs and medications, or underlying pathologies. While many pathways are implicated in pathological pruritus, we are particularly interested in the pruritic response, both chronic and acute, mediated by neurons expressing the Mas-Related G-Protein Coupled Receptor A3 (MrgprA3). Mrgpr’s are a family of GPCRs involved in pruritus and pain which are mainly expressed by sensory neurons and some immune cells. MrgprA3 (A3), known for its involvement in chloroquine-mediated pruritus, is expressed by a specific pruritus-specializing subpopulation of the dorsal root ganglia (DRG) and trigeminal ganglia neurons that innervate the epidermis.
Results and methodology: Using qPCR and in situ hybridization, we found the opioid receptor μ-1 (oprm1) to be expressed by some A3+ neurons in the DRG, raising the question of the involvement of oprm1 and its agonist, β-endorphin, in the A3-mediated pruritic response. Interestingly, we also found the Trypsin-like enzyme, Transmembrane protease serine 11c (Tmprss11c), to be expressed by A3+ neurons as well. To examine its implication in pruritus, we used mice where Tmprss11c conditionally knocked out only in A3+ neurons. We observed a significant decrease in scratching in both acute and long-term pruritic response induced by the A3 agonist; chloroquine, in the Tmprss11c-conditional KO mice compared with WT mice.
Conclusion: These results suggest that Tmprss11c is involved in regulating the pruritic response. Since Trypsin cleaves C-terminal Lysine and Arginine peptide bonds, and β-endorphin is shown to be cleaved by Trypsin, it is possible that Tmprss11c could cleave β-endorphin at any of its five Lysine sites. We propose that although the MrgprA3+ itch-sensing neurons are under chronic suppression by β-endorphin, Tmprss11c constitutively cleaves β-endorphin to maintain itch sensitivity.
P110
Title:
Clinical
Characterization of Chronic Pruritus Across CKD Stages: A
Comprehensive Analysis of Prevalence, Body Distribution, and
Associated Factors
Submitting
author:
Schricker, Severin - Department of General Internal
Medicine and Nephrology, Robert-Bosch-Hospital, Stuttgart, Germany
Additional
Authors:
Schricker S1, Mettang T2 Strutz F2, Rittweiler T2,
Kraft L1, Latus J1, Müller-Kühnle J1 1 Department of General
Internal Medicine and Nephrology, Robert Bosch Krankenhaus (Robert
Bosch Hospital), Stuttgart, Germany 2 Kidney Center Wiesbaden,
Wiesbaden, Germany
Abstract:
INTRODUCTION Chronic pruritus is a prevalent and burdensome symptom in chronic kidney disease (CKD), yet its clinical recognition in pre-dialysis stages remains limited. Evidence on symptom patterns and pathomechanisms outside of dialysis populations is scarce, and early-stage predictors are poorly defined. OBJECTIVES To systematically characterize chronic pruritus in non-dialysis CKD patients, focusing on prevalence, body distribution, severity, and biochemical predictors, particularly parathyroid hormone (PTH) and other mineral metabolism markers. METHODS This cross-sectional study included 94 adult CKD patients with 252 documented visits. Pruritus was assessed using a visual analogue scale (VAS), anatomical localization maps, and structured clinical evaluation. Laboratory parameters (including PTH, phosphate, calcium, vitamin D, CRP), comorbidities, and medication use were recorded. Predictors of chronic and severe pruritus (VAS ≥ 7) were identified using multivariable logistic regression and supervised machine learning (Random Forest, XGBoost). Model performance was evaluated using area under the receiver operating characteristic curve (AUC), and variable importance was visualized. RESULTS Chronic pruritus affected 28.7% of patients and was more frequent in advanced CKD (G3b–5: 24.4%) than in early stages (G1–3a: 9.1%; p = 0.003). The legs, back, and head were the most affected areas, consistent with a non-dermatomal, symmetric distribution pattern. VAS scores correlated with the number of affected regions (r = 0.35), indicating that spatial extent may reflect symptom burden. Serum PTH was the only independent predictor in multivariable analysis (OR = 1.013 per pg/mL; p = 0.012). Machine learning models confirmed PTH as the strongest predictor, followed by BMI and urea (AUC > 0.95). CONCLUSION Chronic pruritus is common even in non-dialysis CKD and increases with disease progression. Our findings support a neuroendocrine mechanism involving PTH, which may serve as a clinically accessible biomarker. Early symptom screening, combined with PTH-modulating strategies, could improve quality of life and guide future therapeutic approaches.
P111
Title:
Itch in
different age groups: Relationship with psychological factors
Submitting
author:
Schut, Christina - DE
Additional
Authors:
*Institute of Medical Psychology,
Justus-Liebig-University Gießen, Germany other authors: Dalgard FJ,
Altunay IK, Balieva F, Bewley A, Elyas A, Evers AWM, Ferreira BR,
Finlay AY, Gieler U, Gracia Cazaña T, Grivcheva Panovska V, Jemec
GB, Legat FJ, Lien L, Lvov A, Marron SE, Misery L, Reich A, Romanov
D, Sampogna F, Spillekom van Koulil S, Ständer S, Szabó C,
Szepietowski JC, Titeca G, Thompson AR, Tomas Aragones L, van Beugen
S, Vulink N, Zeidler C, Kupfer J
Abstract:
Introduction: Itch is related to psychological factors in patients with atopic dermatitis (AD) and psoriasis. However, to the best of our knowledge no study has investigated whether the relationship between psychological factors and itch differs between age-groups. Objectives: To investigate the relationship between itch intensity and psychological factors in patients with psoriasis and AD of different age groups. Methods: Psoriasis- (n=1404) and AD-patients (n=352) from the second study of the European Society for Dermatology and Psychiatry (ESDaP study II) - a multi-centre study conducted in 17 European countries - were included. They completed validated questionnaires to examine stress, stigmatization, anxiety and depression. Itch intensity was measured by a numerical rating scale (NRS) from 0-10. Linear regression models were used to investigate the relationship between itch intensity and psychological variables in different age groups (18-40 years; 41-65 years and > 65 years). Results: Itch intensities did not differ between age groups. In psoriasis-patients older than 65 years, 26.4% of the variance in itch intensity was explained by anxiety and stigmatization, while in psoriasis-patients aged 18-40 years only 10.3% of the variance was explained by these variables. In psoriasis-patients aged 41-65 years, depression, stress and anxiety explained 12.1% of the variance in itch intensity. In AD-patients a similar pattern occured: In elderly patients, 21.8% of the variance in itch intensity was explained by anxiety, while in patients aged 18-40 years 13.7% % was explained by this variable. In AD-patients aged 41-65 years depression accounted for 6.8% of the variance in itch intensity. All correlations were significant and positive (p < 0.05). Conclusion: This study showed that especially in elderly psoriasis- and AD-patients, anxiety is an important variable significantly contributing to itch intensity, which should therefore be considered first with regard to psychological assessment and treatment.
P113
Title:
IL-6
derived from primary afferent sensory neurons contributes to chronic
itch by promoting LCN2 expression in the spinal cord.
Submitting
author:
Shiratori-Hayashi, Miho - 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
Abstract:
Author/Affiliation:Miho Shiratori-Hayashi1,2, Konatsu Asai3, Chiharu Yamaguchi3, Honami Toyonaga3, Mitsutoshi Tominaga1, Yoshitoshi Kasuya2, Kenji Takamori1, Makoto Tsuda3 1. Juntendo Itch Research Center (JIRC), Institute for Environmental and Gender Specific Medicine, Juntendo Univ. Graduate school of Medicine 2. Department of Molecular and Systems Pharmacology, Faculty of Pharmacy, Juntendo University 3. Department of Molecular and Systems Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University Previously, we demonstrated that the transcription factor STAT3 that expressed in spinal cord astrocytes, is activated in a mouse model of chronic itch. We also showed that LCN2, expressed in a STAT3-dependent manner, plays a role in itch hypersensitivity by enhancing GRPR-positive neuron responsiveness to GRP (Nat Med, 2015; JACI, 2020). Previous experiments have shown that STAT3 activation in astrocytes depends on skin damage associated with prolonged scratching behavior and activity of primary afferent sensory neurons. Thus, the purpose of this study is to identify factors derived from primary sensory neurons that induce astrocyte STAT3 activation and subsequent LCN2 expression. Results showed increased IL-6 expression in the dorsal root ganglion (DRG) of mice with DCP-induced contact dermatitis, a chronic itch model. This increased expression was suppressed when the mice's hind paw nails were trimmed to prevent scratch-induced skin damage. Additionally, selectively suppressing IL-6 expression in primary sensory neurons using adeno-associated viral vectors improved chronic itch behavior and reduced LCN2 expression in the spinal cord. These results suggest that IL-6, whose expression increases in primary sensory neurons due to skin damage caused by scratching behavior, contributes to chronic itch via increasing LCN2 expression in the spinal cord.
P116
Title:
Impact
of mechanical stress in chronic pruritus pathogenesis: a multiomics
approach
Submitting
author:
Teitge, Esther - University Hospital Münster, Section
for Pruritus Medicine, Department of Dermatology and Center for
Chronic Pruritus, Münster, Germany
Additional
Authors:
H. Renkert (1), C. Zeidler (1), S. König (2), S.
Ständer (1), H. Wiegmann (1), K. Agelopoulos (1) (1) University
Hospital Münster, Section for Pruritus Medicine, Department of
Dermatology and Center for Chronic Pruritus, Münster, Germany (2)
University of Münster, IZKF Core Unit Proteomics, Münster, Germany
Abstract:
Introduction Chronic nodular prurigo (CNPG) is a chronic inflammatory skin disease defined by persistent and compulsive scratching. This self-perpetuating itch-scratch cycle is central to the pathogenesis and progression of CNPG. Mechanistically, repeated scratching exerts sustained mechanical stress on cutaneous cells, particularly keratinocytes and dermal fibroblasts, which are key players in skin homeostasis and immune responses. Objectives Define molecular mechanisms by which mechanical forces modulate cellular behavior in CNPG. Methods We utilized a controlled in vitro scratch model to investigate effects of mechanical stress on primary human keratinocytes isolated from CNPG patients. By employing a cytostretcher platform, we simulated biomechanical strain to mimic the physical forces experienced by epidermal cells during chronic scratching. We subsequently performed integrated transcriptomic (RNAseq) and proteomic (MassSpec) analyses to characterize the cellular response to this mechanical insult. Results Our multi-omics approach revealed a robust deregulation of a wide array of genes and proteins. Notably, we observed a significant enrichment of key mediators of type 2 inflammation including IL-4/-13 signaling alongside genes implicated in neuroinflammatory processes, axonal guidance, cutaneous innervation, and neuronal projection (e.g. SEMA3A, CDK5, TNC). Additionally, alterations in components associated with epigenetic regulation were identified, suggesting a lasting impact of mechanical stress on gene expression programs. Conclusion Taken together, these findings highlight that mechanical stress, in isolation, is sufficient to provoke profound molecular changes in keratinocytes. Specifically, it induces the dysregulation of pathways linked to pruritus, inflammation, and neuronal communication. These results underscore the critical role of biomechanical factors in the pathophysiology of CNPG and provide mechanistic insights into how chronic scratching exacerbates disease progression through cellular reprogramming.
P117
Title:
Loss of
IL-22 responsive gene Gm94 affects mechanical alloknesis in a
sex-specific manner
Submitting
author:
Tobita, Tomohiro - 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
Abstract:
Tomohiro Tobita1, Mitsutoshi Tominaga1, Kenji Takamori1, 2 1) Juntendo Itch Research Center (JIRC), Institute for Environmental and Gender- Specific Medicine, Graduate School of Medicine, Juntendo University, Chiba, Japan 2) Department of Dermatology, Juntendo University Urayasu Hospital, Chiba, Japan Introduction: Interleukin-22 (IL-22), a member of the IL-10 family, is involved in immuno-regulatory responses. It promotes epidermal keratinocyte proliferation while inhibiting differentiation. Epidermal hyperplasia, characterized by keratinocyte hyperproliferation, occurs in chronic inflammatory skin diseases such as atopic dermatitis (AD) and psoriasis. Our previous study reported that epidermal thickness correlated with VAS and EASI scores in AD patients. However, the relationship between IL-22 and itch remains unclear. Objectives: This study aimed to investigate the mechanisms linking IL-22 to itch. To achieve this, we focused on genes regulated by IL-22 in keratinocytes. Methods: IL-22 responsive genes were selected by reanalyzing AD transcriptomic data from public databases. Candidate genes were validated using skin samples from mouse models of pruritic skin disease (dry skin, AD, and psoriasis models). Further validation was performed in human epidermal keratinocytes treated with IL-22. Gene knockout (KO) mice were generated using the CRISPR/Cas9 system. Results: We identified C5orf46 (Chromosome 5 open reading frame 46; mouse homolog Gm94) as an IL-22 responsive gene. C5orf46/Gm94-KO mice developed normally and exhibited normal skin morphology. Loss of C5orf46/Gm94 exacerbated mechanical alloknesis, in a sex-dependent manner. Conclusion: We identified C5orf46/Gm94 as an IL-22-responsive gene. C5orf46/Gm94-KO mice exhibited sex-dependent mechanical alloknesis, suggesting that C5orf46/Gm94 may play a role in mediating sex-specific itch sensations.
P118
Title:
Pathogenesis
of atopic dermatitis focusing on the serine protease-IL-33-regulatory
T-cell axis
Submitting
author:
Toyama, Sumika - Juntendo Itch Research Center (JIRC),
Institute for Environmental and Gender-Specific Medicine, Juntendo
University Graduate School of Medicine, 2-1-1 Tomioka, Urayasu,
Chiba, Japan
Abstract:
Introduction: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by dry skin resulting from skin barrier disruption. Regulatory T cells (Tregs) play a crucial role in maintaining immune homeostasis and self-tolerance. Objectives: This study aims to elucidate the mechanisms underlying impaired Treg migration in AD, focusing on the role of antigen-derived serine proteases in modulating IL-33 activity. Methods: A murine model of skin barrier disruption was established through repeated topical application of 4% sodium dodecyl sulfate (SDS). An AD model was created by combining 4% SDS application with house dust mite (HDM) exposure. Biochemical analyses were conducted to assess IL-33 cleavage by serine proteases and the effect of serine protease inhibitors. Treg migration was evaluated, and the therapeutic potential of serine protease inhibitors and Treg inducers was assessed in the AD model. Results: In the skin barrier disruption model, activated IL-33 derived from keratinocytes promoted Treg migration, facilitating transitions between healthy and inflammatory states. However, in the AD model, Treg migration was significantly reduced. Biochemical analyses revealed that IL-33 was cleaved by antigen-derived serine proteases, a process inhibited by serine protease inhibitors. Cleaved IL-33 lost its ability to promote Treg migration. Administration of serine protease inhibitors and Treg inducers ameliorated AD symptoms in the murine model. Conclusion: Cleavage of IL-33 by antigen-derived serine proteases impairs Treg recruitment, contributing to sustained inflammation in AD. Therapeutic strategies targeting serine protease activity and enhancing Treg function may offer novel approaches for AD treatment.
P119
Title:
Molecular
Pharmacological Analysis of 20 Japanese Traditional Herbal “Kampo”
Medicines in Pruritus Modulation: Implications for Atopic Dermatitis
Submitting
author:
Tsuji, Masao - Juntendo Itch Research Center (JIRC),
Institute for Environmental and Gender-Specific Medicine, Juntendo
University Graduate School of Medicine, Chiba, Japan / Ominedo
Pharmaceutical Industry Co., Ltd. Nara, Japan.
Additional
Authors:
Jun Utsumi/Juntendo Itch Research Center (JIRC),
Institute for Environmental and Gender-Specific Medicine, Juntendo
University Graduate School of Medicine, Chiba, Japan. Koichi
Miyakawa/Department of Psychiatry, Juntendo University Urayasu
Hospital, Chiba, Japan. Yayoi Kamata/Juntendo Itch Research Center
(JIRC), Institute for Environmental and Gender-Specific Medicine,
Juntendo University Graduate School of Medicine, Chiba, Japan.
Kenichiro Handa/Ominedo Pharmaceutical Industry Co., Ltd. Nara,
Japan. Ryosuke Takemoto/Ominedo Pharmaceutical Industry Co., Ltd.
Nara, Japan. Hiroyuki Shibasaki/Ominedo Pharmaceutical Industry Co.,
Ltd. Nara, Mitsutoshi Tominaga/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.
Abstract:
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. In Japan, traditional Japanese herbal remedies formulations (“Kampo” medicines) have been developed since approximately 400 years ago and continue to be used in clinical practice to date. 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 20 approved Kampo medicines, 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 Kampo medicines downregulated genes involved in itch amplification and upregulated those related to skin barrier maintenance. These favourable patterns were observed not only in known Kampo medicines for dermatological disorders but in use for gastrointestinal and menopausal disorders. Machine learning visualization (t-SNE) of gene expression profiles supported these trends. These findings suggest that certain Kampo medicines may simultaneously suppress itch signaling and enhance skin barrier function, offering potential as novel therapeutic options for atopic dermatitis.
P120
Title:
Kappa
opioid receptor agonists possess antipruritic and
keratinocyte-protective effects: A novel therapeutic potential for
the treatment of anticancer drug-induced skin disorders
Submitting
author:
Utsumi, Jun - Juntendo Itch Research Center (JIRC),
Institute for Environmental and Gender-Specific Medicine, Juntendo
University Graduate School of Medicine, Chiba, Japan/Tokyo University
of Pharmacy and Life Sciences, Tokyo, Japan.
Additional
Authors:
Sachiko Tanaka/Tokyo University of Pharmacy and Life
Sciences, Tokyo, Japan. Kenichi Suzuki/Tokyo University of Pharmacy
and Life Sciences, Tokyo, Japan. Hisanori Shimizu/Cancer Institute
Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
Yayoi Kamata/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. Kenji Takamori/Juntendo
Itch Research Center (JIRC), Institute for Environmental and
Gender-Specific Medicine, Juntendo University Graduate School of
Medicine, Chiba, Japan.
Abstract:
Kappa (κ) opioid receptor agonists have been clinically applied as antipruritic agents in patients with end-stage renal disease undergoing dialysis. We newly discovered that they induce the epithelial cell proliferation process. Based on this finding, we evaluated to apply κ-opioid receptor agonists to Hand-Foot Syndrome (HFS) and Hand-Foot Skin Reaction (HFSR). HFS/HFSR have been occurring as cancer chemotherapy-induced serious epithelial toxicities known to involve pathologically specific damage to the epidermis with inflammation, edema, erythema, pain, and pruritus. These symptoms significantly impair patients’ quality of life (QOL), however, no effective treatment has been established over the past two decades. To further investigation, we exposed normal human epidermal keratinocytes to two typical anticancer agents, capecitabine (CP, a 5‑fluorouracil compound) and regorafenib (REG, a multikinase inhibitor), and analyzed gene expression related to skin toxicity via transcriptomic profiling. Visualization of drug-induced gene expression changes using a machine learning t‑SNE algorithm revealed partial similarity and weak correlation between CP and REG. Among down-regulated gene sets, the top Gene Ontology term was “epidermis development” (GO:0008544), indicating strong anti-proliferative effects. Notably, CP suppressed genes involved in early keratinocyte differentiation, while REG suppressed those involved in late differentiation. Simultaneously we identified epithelial proliferation signaling in keratinocytes to response to κ-opioid receptor agonists, nalfurafine and difelikefalin. When keratinocytes were treated with either nalfurafine or difelikefalin in the presence of CP or REG, both cell proliferation and protective effects were observed. Furthermore, these effects were enhanced by glycyrrhetinic acid. These findings suggest that κ-opioid receptor agonists offer a novel therapeutic option for the treatment of HFS/HFSR via their dual action of analgesia/antipruritic effects and keratinocyte protection when used as topical agents.
P121
Title:
A
sympathetic-keratinocyte axis inhibits chronic itch
Submitting
author:
Wang, Fang - Dermatology Hospital of Southern Medical
University, 2 Lujing Road, Guangzhou, Guangdong, China
Abstract:
Introduction: The skin is densely innervated by various nerves, including sensory nerves and sympathetic nerves. While sensory nerves are known to mediate the transmission of itch signals in chronic pruritic diseases, the role of the other major type—sympathetic nerves—in chronic itch remains largely unknown. Objectives: This study aimed to characterize alterations in cutaneous sympathetic innervation in chronic itch, determine their functional impact on itch sensation, and elucidate underlying molecular mechanisms. Methods: Sympathetic nerve architecture was analyzed using whole-mount immunofluorescence in a murine dry skin model (acetone–ether–water, AEW). Functional roles were assessed via genetic, chemogenetic, and pharmacologic gain/loss-of-function approaches, with itch quantified by scratching behavior. Candidate neurotrophic factors and pruritogens were identified using public single-cell RNA-seq datasets and validated by immunoblotting and immunostaining. Results: In the AEW model, cutaneous sympathetic nerve density was significantly reduced. Chemogenetic stimulation of sympathetic nerves reduced scratching, whereas sympathetic blockades or ablation increased itch behavior. Modulating sympathetic neurotransmitter signaling through topical agonists/antagonists significantly influenced scratching behavior. Mechanistically, this regulation was linked to altered IL-33 localization within keratinocytes. Notably, behavioral activation of sympathetic tone through elevated platform standing (EPS) also suppressed itch responses. Conclusion: This study identifies cutaneous sympathetic nerves as active suppressors of chronic itch, operating through IL-33 in keratinocytes. These findings reveal novel neuromodulatory pathways and potential therapeutic targets for treating chronic pruritus.
P123
Title:
From
Itch to Insight: Interpretable Machine Learning Enhances Pruritus
Subtype Differentiation
Submitting
author:
Wiegmann, Henning - 1. Section Pruritus Medicine,
Department of Dermatology and Center for Chronic Pruritus, University
of Münster, Germany
Additional
Authors:
Michael Fujarski (2), Claudia Zeidler (1), Julian
Varghese (2), Sonja Ständer (1) 1. Section Pruritus Medicine,
Department of Dermatology and Center for Chronic Pruritus, University
of Münster, Germany 2. Institute of Medical Informatics, University
of Münster, Germany.
Abstract:
Introduction Pruritus is common in dermatology, affecting about a third of patients. Chronic pruritus (CP)—lasting despite treatment—is the main issue for 62% of patients. Diagnosing CP requires a multidisciplinary approach, using thorough histories and patient-reported outcome measures (PROMs). Machine learning advances now allow better analysis of complex clinical data, enhancing diagnosis. Objectve The aim was to identify important parameters and to develop robust predictive diagnostic tool. Methods >From 03/2012 to 10/2023, we analyzed data from 9,989 retrospective and 1,821 prospective patients, including hospital data and PROMs. Missing data were imputed; dimensionality reduction (PCA, SVD) was used for feature selection. CatBoost model with SHAP analysis provided interpretability. Robustness was tested via 5-fold cross-validation. Results AUROC ranged from 0.89 to 1.00, with mean balanced accuracy of 90.3%. Key predictors were age, lesion features, and pruritus location. ItchyQoL and Neuroderm PROMs outperformed HADS, DLQI, and PNQ. Removing less informative items slightly reduced performance. Prospective validation showed a small accuracy drop (88.5%), with stable AUROC, confirming model generalizability. Conclusion Machine learning effectively classifies pruritus subtypes, and removing non-contributory items improves specificity without major predictive loss. However, clinical judgment remains essential for accurate diagnosis, supporting precision medicine and easing patient burden.
P124
Title:
Involvement
of the S1P-S1PR2 Axis in Itch Associated with Canine Atopic
Dermatitis
Submitting
author:
Xie, Tong - Institute of Pharmacology and Toxicology,
School of Veterinary Medicine, Freie Universität Berlin, Berlin,
Germany
Abstract:
Tong Xie1, Anne Dalponte1, Burkhard Kleuser2, Wolfgang Bäumer1 1Institute of Pharmacology and Toxicology, School of Veterinary Medicine, Freie Universität Berlin, Berlin 2Institute of Pharmacy, Department of Pharmacology and Toxicology, Freie Universität Berlin, Berlin Sphingosine 1-phosphate (S1P) has been found to play a regulatory role in inflammatory skin diseases like atopic dermatitis (AD). Among its receptors, S1P receptor 2 (S1PR2) notably regulates epithelial barrier function and immune cell activity. However, the role of the S1P–S1PR2 axis in mediating itch associated with canine AD remains poorly understood. This study aims to investigate its involvement using a canine model of AD. In in vitro studies, calcium imaging was used to evaluate the responses of sensory dorsal root ganglion (DRG) neurons isolated from BALB/c and C57BL/6 mice exposed to S1P, with or without pre-incubation using JTE-013 (an S1PR2 antagonist) or FTY720P (an S1P analogue). Responses of DRG neurons from wild-type and S1PR2 knockout (KO) mice to S1P, CYM5520 (S1PR2 agonist), or capsaicin were also compared. In the in vivo study, laboratory beagles were sensitized to house dust mite (HDM) allergen to induce canine AD. In a blinded, cross-over experimental design, dogs were topically treated with either JTE-013 or vehicle control initiated three days prior to HDM challenge and continued for three days. Itch behavior was assessed once after the challenge, while skin lesions were evaluated daily for three consecutive days. The results demonstrated that JTE-013 and FTY720P significantly reduced sensory neuron activation in response to S1P in mice. Additionally, responses to S1P, CYM5520, and capsaicin were significantly lower in DRG of S1PR2-KO-mice compared to wild-type controls in vitro. Importantly, topical treatment with JTE-013 significantly decreased itch events in the dog model of AD in vivo. In conclusion, our study indicates that the S1P-S1PR2 axis may play a role as a therapeutic target in itch associated with canine AD.
P125
Title:
Validation
of an AI-Enabled Wearable Sensor (ADAM) for Daytime Scratching Using
Real-World Confounders
Submitting
author:
Xu, Shuai - Sibel Health
Abstract:
Introduction While nighttime scratching has been studied with wearables and imaging techniques including our ADAM, objective assessment of daytime scratching remains limited due to confounding daily activities and technology acceptability. Objectives In this work, we developed a new AI algorithm using ADAM for classifying daytime scratching across multiple anatomical sites against real-world confounders. Methods A total of 42 healthy adult subjects contributed two validation datasets totaling 24,941 scratch samples and 23,139 confounder samples. Scratching behaviors were recorded across 12 body sites. Confounders included 15 common daily activities (e.g., typing, brushing teeth, fabric rubbing). The AI classifier performance was assessed via accuracy, precision, recall, specificity, and Matthews correlation coefficient (MCC), with receiver operating characteristic (ROC) and precision-recall (PR) curve analyses. Results The classifier achieved an average accuracy of 93.9% for scratch detection across all anatomical sites. Forearm (97.3%) and cheek (96.8%) had the highest site-specific accuracies, while the head (89.4%) was the lowest and the only site below 90% classification accuracy. Confounder discrimination was strong with an average accuracy of 93.5%. Keyboard typing (99.67%), texting (99.22%), and hand clapping (98.89%) were classified with the highest accuracy, while fabric rubbing remained the lowest at 84.2%. The overall ROC-AUC and PR-AUC were 0.98 and 0.97, respectively. Conclusion The ADAM wearable system and AI algorithm demonstrated robust accuracy in identifying daytime scratching across diverse body sites and differentiating from common non-scratch behaviors. These findings support its use in continuous, real-world assessment of daytime scratching. Future efforts should include validation in specific itchy conditions such as atopic dermatitis.
P126
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
Submitting
author:
Zeng, Hekun - State Key Laboratory of Bioactive
Molecules and Druggability Assessment, Jinan University, Huangpu
Avenue West 601, Guangzhou, Guangdong, China
Additional
Authors:
Zhe Zhang, Dan Zhou, Ranjing Wang, Alexei Verkhratsky,
Hong Nie*.
Abstract:
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.
P128
Title:
Selective
Involvement of JAK1 Signaling in the Development of Mechanical
Alloknesis in Atopic Dermatitis
Submitting
author:
Zuo, Ying - Juntendo Itch Research Center (JIRC),
Institute for Environmental and Gender Specific Medicine, Juntendo
University Graduate School of Medicine
Abstract:
Author/Affiliation Ying Zuo 1, Sumika Toyama 1, Hiroyuki Akiba1 Soichiro Yoshikawa1, Mitsutoshi Tominaga 1, Kenji Takamori 1,2 1 Juntendo Itch Research Center (JIRC), Institute for Environmental and Gender Specific Medicine, Juntendo University Graduate School of Medicine, Japan 2 Department of Dermatology, Juntendo University Urayasu Hospital, Japan Introduction Chronic pruritus is a defining feature of atopic dermatitis (AD), which exacerbates skin inflammation through scratching and significantly impairs patients' quality of life. Among the sensory abnormalities observed in AD, the mechanical alloknesis (m-alloknesis), which is an itch sensitization to normally innocuous mechanical stimuli, stands out as a potential contributor to the itch-scratch cycle. While Janus kinase (JAK) inhibitors have shown therapeutic efficacy in alleviating AD symptoms, their role in modulating m-alloknesis remains unclear. Objectives This study aims to the role of JAK signaling in mediating AD-associated m-alloknesis in NC/Nga mice. Methods We compared m-alloknesis scores in an AD mouse model (4% SDS and house dust mite (HDM) application to NC/Nga mice) following treatment with three JAK inhibitors: the JAK 1/2 inhibitor baricitinib, the selective JAK1 inhibitor abrocitinib, and the selective JAK2 inhibitor AZ960 or vehicle control. Results Our analyses revealed that both the JAK1/2 inhibitor baricitinib and the selective JAK1 inhibitor abrocitinib significantly reduced m-alloknesis scores in AD mice within 2 hours post-administration, whereas the JAK2-selective inhibitor AZ960 had no significant effect. None of the JAK inhibitors had notable improvement on skin lesions or skin barrier function within the short observation period. These findings suggest that JAK1, but not JAK2, signaling is critical for AD-associated m-alloknesis. Conclusion Our findings highlighted the potential initiating role of JAK1-dependent cytokines, rather than JAK2-dependent ones, in the pathogenesis of AD-induced itch sensitization, warranting further investigation into their specific contributions.
P131
Title:
Patient-reported
Treatment Priorities in Pruriginous Dermatoses: Insights from
Patients with Chronic Prurigo
Submitting
author:
Loewenthal, Joyce-Anahi - Center for Chronic Pruritus,
Department of Dermatology, University Hospital Münster, Germany
Abstract:
Background: Chronic prurigo (CPG), including prurigo nodularis, is a skin disease characterized by severe itch and pruriginous lesions, leading to significant impairment in quality of life. Due to its chronic course and burden, patient-centered treatment strategies are essential to improve therapeutic outcomes. Objectives: This study aimed to identify the most distressing symptoms and key therapeutic goals from the perspective of patients affected by CPG. Methods: This single-center, prospective, non-interventional study included adult CPG patients (N=171) with active moderate-to-severe disease (Group A; NRS ≥ 7; 56.1%, n = 96) and those who considered themselves successfully treated (Group B; 43.9%, n = 75).). Patients reported their most distressing symptoms and prioritized treatment goals using both open-ended interviews and predefined ranking formats. Results: Across all participants, pruritus was the most burdensome symptom (99.4% in open responses; 82.5% in symptom rankings), followed by the urge to scratch (48.0% / 66.1%), presence (45.6% / 21.1%) and bleeding (27.5% / 24.0%) of lesions and sleep disturbances due to CPG (23.4% / 13.5%). Other symptoms included for example feelings of shame (14%) and restrictions in leisure activities (2.9%). Regarding treatment goals, the most frequently mentied The most frequently mentioned therapy goals were reduction (48.5%) or complete disappearance (43.9%) of itch, healing of skin lesions (43.3%), relief of sleep disturbances (15.2%), and improved overall quality of life (5.8%). Among ten predefined therapeutic aims, pruritus reduction was ranked top priority by 40.4% of patients, followed by interruption of scratching (32.7%) as top 2 and itch dissappearance (12.3%) as top 3. Conclusion: Patients with CPG identify pruritus control and lesion healing as their primary symptoms and most frequently mentioned therapy goals. The substantial psychological and social burdens reported highlight the necessity of therapeutic approaches addressing both physical symptoms and psychosocial well-being.
P132
Title:
Chronic
Prurigo: Preferences in patients’ treatment goals depending on
disease severity
Submitting
author:
Stahl, Lea-Sophie - Department of Dermatology and Center
for Chronic Pruritus, University Hospital Münster, Germany Von
Esmarch Str. 58, 48149 Münster, Germany Phone: +49- 251 8356501
Additional
Authors:
L.S. Stahl1, C. Zeidler1, J. Loewenthal1, S. Royeck1,
F. Witte1, S. Ständer1 1 Department of Dermatology and Center for
Chronic Pruritus, University Hospital Münster, Germany Keywords:
prurigo nodularis, chronic prurigo, itch, treatment goals Word count:
260 Ethics statement: The patients in this manuscript have given
written informed consent to publication of their case details. The
study was approved by the local IRB (no. 2023-389-f-S).
Abstract:
Introduction: Chronic prurigo (CPG), including prurigo nodularis, is a chronic, burdensome skin disease characterized by persistent itch and pruriginous lesions. It significantly impairs quality of life and is associated with complex, evolving treatment needs. Objectives: This study aimed to examine how patient-reported treatment goals change during the course of therapy depending on disease stage. By analyzing therapeutic priorities in different patient groups, we identified patterns in how expectations shift over time and with disease burden. Methods: This prospective, single-center, non-interventional study included adult patients with CPG. Participants were divided into two groups: those with moderate-to-severe disease and intense pruritus (WI-NRS ≥ 7) (Group A; 56.1%, n = 96), and those who considered themselves successfully treated (Group B; 43.9%, n = 75). Structured interviews assessed patients’ most important treatment goals through open interviews and ranking of ten predefined therapy objectives. Results: A clear shift in priorities was observed: patients with active, severe disease (Group A) prioritized pruritus reduction (rank 1; 60.4%), followed by partial lesion healing (rank 5; 21.9%). In contrast, successfully treated patients (Group B) emphasized complete pruritus remission (rank 1; 54.7%) and complete lesion healing (rank 3; 12.5%). Relief from sleep disturbances was ranked slightly higher by Group A (rank 7) than by Group B (rank 8; 9.3%), reflecting greater symptom burden. Conclusion: Across all disease stages, pruritus relief and lesion improvement are key goals. However, patient preferences shift with disease severity. These findings emphasize the need for adaptable treatment strategies that reflect current disease status. Future research should focus on incorporating these evolving needs into personalized care approaches.
P133
Title:
Patient
expectations regarding timeframes for itch reduction and lesion
healing in the treatment of chronic prurigo
Submitting
author:
Stahl, Lea-Sophie - Department of Dermatology and Center
for Chronic Pruritus, University Hospital Münster, Germany Von
Esmarch Str. 58, 48149 Münster, Germany Phone: +49- 251 8356501
Additional
Authors:
L.S. Stahl1, C. Zeidler1, J. Loewenthal1, S. Royeck1,
F. Witte1, S. Ständer1 1 Department of Dermatology and Center for
Chronic Pruritus, University Hospital Münster, Germany Keywords:
prurigo nodularis, chronic prurigo, itch, treatment goals Word count:
299 The patients in this manuscript have given written informed
consent to publication of their case details. The study was approved
by the local IRB (no. 2023-389-f-S).
Abstract:
Introduction Chronic prurigo (CPG) is a burdensome skin disease characterized by intensive pruritus and pruriginous lesions. With emerging therapies such as dupilumab, understanding patient expectations regarding the timing of therapeutic outcomes is essential for individual treatment. Objectives This study examined patient-reported expectations regarding the time needed for achieving itch relief and lesion healing in CPG treatment. Methods 171 adultw with CPG participated in structured interviews about their expected timeframes for itch relief and lesion healing. Two groups were defined: patients with moderate-to-severe disease and itch (WI-NRS ≥ 7; Group A, 56.1%, n = 96), and those who considered themselves successfully treated (Group B, 43.9%, n = 75). Patients identified optimal and acceptable timeframes for achieving a ≥4-point itch reduction targeting WI-NRS 0/1 and lesion healing (IGA 0/1). Results For a relevant itch reduction, the most frequently reported ideal timeframe was one month for Group A (54.2%), three months for Group B (50.7%). Acceptable timeframes extended to three months for Group A (51.0%), six months for Group B (50.7%). For complete itch relief (WI-NRS 0/1), both groups most frequently selected six months as ideal (Group A: 39.6%; Group B: 37.3%). Twelve months were acceptable for Group A (37.5%), while Group B showed no consistent preference regarding the complete itch relief. Regarding lesion healing (IGA 0/1), the preferred ideal timeframe was three months in Group A (42.7%), six months in Group B (44.0%). Acceptable timeframes were six months in Group A (36.5%), twelve months in Group B (38.7%). Conclusion Patients with severe CPG reported shorter timeframes for treatment goals than those who felt successfully treated, reflecting a more urgent need for relief. In contrast, previously treated patients showed more realistic expectations. These findings underline the strong desire for rapid itch relief and the importance of managing expectations, especially in active disease.
P134
Title:
Prurigo
Activity and Severity Score and Investigator Global Assessment-
Psychometric analyses of the physician-reported outcome measures for
chronic Prurigo
Submitting
author:
Zeidler, Claudia - University Hospital Münster,
Department of Dermatology and Center for Chronic Pruritus.
Von-Esmarch-Str 58, 48149 Münster, Germany
Additional
Authors:
Sonja Ständer University Hospital Münster, Department
of Dermatology and Center for Chronic Pruritus. Von-Esmarch-Str. 58,
48149 Münster, Germany
Abstract:
Introduction: Reliable physician-reported outcome measures are essential for monitoring treatment response in chronic prurigo (CPG; prurigo nodularis). The Prurigo Activity and Severity (PAS) Score and the Investigator Global Assessment for CPG (IGA-CPG) are standardized physician documentation forms previously validated for content and inter-rater reliability. In this longitudinal study, additional psychometric analyses were performed to further characterize the measurement properties. Methods: Clinical and demographic data from 418 patients with CPG were recorded during regular consultations. Assessments included itch intensity scales—the Numerical Rating Scale (NRS), Visual Analog Scale (VAS), Verbal Rating Scale (VRS)—quality of life (QoL) instruments like the Dermatology Life Quality Index (DLQI) and ItchyQoL, as well as physician-reported outcome measures including PAS and IGA-CPG. Additionally, in 90 patients an anchor-based patient questionnaire was used to evaluate subjective changes in symptom severity- Results: The PAS and IGA demonstrated independence from age, sex, CPG etiology, CPG-type and skin type. A significant correlation was observed between total PAS score and IGA-CPG scores. Changes in disease severity measured by IGA-CPG closely corresponded with changes in itch intensity and scores in QoL measurements (p < 0.001). The total number of pruriginous lesions and PAS scores were strong predictors of IGA-CPG changes (p < 0.001). A minimal clinically important improvement in pruritus intensity assessed by the anchor questionnaire was associated with a reduction of 19% (baseline to follow-up visit 1) and 43% (baseline to follow-up visit 2) in the total number of pruriginous lesions. Also he total PAS score decreased by 0.42 points (baseline to follow-up 1) and by 1.86 points (baseline to follow-up 2) respectively. Conclusion: The IGA-CPG and PAS are objective tools for assessing disease activity and severity of CPG. Their independence from demographic and clinical factors and strong correlation with itch intensity and number of lesions support their application in both research and clinical practice.
P135
Title:
Psychological
Predictors of Histaminergic and Non-Histaminergic Itch Intensity
Submitting
author:
Aliotta, Giulia Erica - Center for Neuroplasticity and
Pain (CNAP), SMI, Department of Health Science and Technology,
Faculty of Medicine, Aalborg University, Denmark
Abstract:
Introduction: In recent years, the understanding of the biological mechanisms of itch has improved. Nevertheless, it has been proposed that the biopsychosocial model may be applied to provide a full explanation of itch perception. This is supported by evidence linking itch intensity, personality traits, and psychological factors (stress, anxiety, worrying). Among them, Behavioral Activation System (BAS, which drives approach behavior), Behavioral Inhibition System (BIS, tendency to anxiety) and Fight–Flight–Freeze System (FFFS, tendency to fear), and catastrophizing could influence itch perception, but they remain unexplored in the literature.
Aim: This study aimed to determine whether BAS, BIS, and FFFS predict histaminergic and non-histaminergic itch perception, and to explore the relationship between catastrophizing and itch.
Method: Data from 37 healthy volunteers have been analyzed (24 females and 13 males, 25.4±5.0 years). The study consists of two experimental sessions 3 days apart. During the first session, participants filled out the Reinforcement Sensitivity Theory – Personality Questionnaire, followed by 9-minute application of histamine (histaminergic itch) or cowhage (non-histaminergic itch). Itch intensity was continuously measured using a VAS scale, from which peak intensity and AUC (area under the curve) were derived. After the application, participants completed the Itch Catastrophizing Scale (ICS) and Learned Helplessness Scale (LHS). The second session involved alternate pruritogen (randomized across sessions), followed again by completion of the ICS and LHS.
Results: Histaminergic itch was predicted by FFFS (peak: R2=0.260, AUC: R2=0.254, p<0.05), while none of the personality traits predicted non-histaminergic itch. Histamine-induced itch positively correlated with ICS (total score/magnification/helplessness, peak: r=0.401/r=0.404/r=0.432, p<0.05) and LHS (peak/AUC: r=0.530/r=0.483, p<0.01). Cowhage-induced itch positively correlated with ICS (total score/rumination/helplessness, peak: r=0.469/r=0.525/r=0.390, AUC: r=0.538/r=0.568/r=0.462, p<0.01), while only AUC positively correlated with magnification and LHS (r=0.360/r=0.336, p<0.05).
Conclusion: Psychological factors can modulate itch perception in healthy subjects and may serve as contributing mechanisms in chronic itch.
P137
Title:
Predictors
of perceived stress, perceived stigmatization and body dysmorphia in
patients with chronic prurigo: results from an observational
crosssectional multicentre European Study in 17 countries
Submitting
author:
Brenaut, Emilie - University hospital of brest,
Dermatology, France
Abstract:
Background: Patients with chronic prurigo (CPG) often remain unresponsive to treatment and suffer from impaired quality of life due to their chronic itch-scratch cycle and associated comorbidity burden. Previous studies highlighted that anxiety, depression and suicidal ideation are frequent in patients with chronic prurigo. Objective: To analyze perceived stress, stigmatization, body dysmorphia and anxiety/depression in CPG patients and compare them to controls, and then to identify variables/predictors of them. Methods: This study is part of a cross-sectional multicenter study in 17 European countries including 5487 consecutive patients and 2808 controls. Stress was analyzed with the Perceived Scale Stress, stigmatization with the Perceived Stigmatization Questionnaire, body dysmorphia with the Dysmorphic Concern Questionnaire and anxiety/depression with the Patient Health Questionnaire. Results: 127 individuals with prurigo were included (59.1% of women, mean age 54.7 years). Patients were older and had more comorbidities than controls. 57.2% of CPG patients were satisfied with their appearance vs 74.1 % of controls (p<0.0001). In multivariate analysis, the levels of stress (OR 2.81 [1.64; 3.99]), stigmatization (OR 0.122 [0.046; 0.198]), body dysmorphia (OR 7.30 [3.57; 14.9]), anxiety and depression (OR 2.124 [1.655; 2.593]) were significantly higher than in controls. Stigmatization was associated with higher stress and having a severe disease, stress with younger age and lower income, depression and anxiety with lower income and higher itch intensity, body dysmorphia with younger age and dissatisfaction with appearance. This suggests that patients who are previously vulnerable for other reasons can have more psychological consequences than the others and that their vulnerability is enhanced by CPG, and especially itch. Conclusion: CPG patients have high levels of perceived stress, perceived stigmatization and body dysmorphic, with are closely related. They are partly related to sociodemographic factors like younger age or lower income as well as to other psychological and disease-related factors.
P138
Title:
Beyond
Blisters: Mapping the Burden of Itch in Autoimmune Blistering
Diseases
Submitting
author:
Edwards, Elise - University of Miami Miller School of
Medicine, Dr. Phillip Frost Department of Dermatology and Cutaneous
Surgery, 1600 NW 10th Ave #1140, Miami, FL 33136, USA
Additional
Authors:
Rahul Aggarwal, Marieta Papanikolaou, Gil Yosipovitch;
University of Miami Miller School of Medicine, Dr. Phillip Frost
Department of Dermatology and Cutaneous Surgery, 1600 NW 10th Ave
#1140, Miami, FL 33136, USA
Abstract:
Introduction: Autoimmune blistering diseases (AIBDs), including bullous pemphigoid (BP) and pemphigus variants, are antibody-mediated dermatoses in which pruritus is a prominent but understudied symptom. Itch is increasingly recognized as a contributor to disease burden and may be an early marker of disease activity, particularly in BP. Objectives: To map and synthesize the literature on pruritus in AIBDs, including symptom presentation, mechanisms, and use of validated assessment tools. Methods: A scoping review was conducted using PRISMA-ScR methodology (OSF registration: https://doi.org/10.17605/OSF.IO/V8RPW). MEDLINE and EMBASE were searched through February 2025. Of 2,309 records identified, 128 met inclusion criteria following duplicate removal and full-text review. Results: The most frequently studied disease was BP (n=75), followed by dermatitis herpetiformis (n=19), pemphigus vulgaris (n=8), pemphigus foliaceus (n=7), lichen planus pemphigoides (n=4), epidermolysis bullosa acquisita (n=3), mucous membrane pemphigoid (n=2), and paraneoplastic pemphigus (n=2). Study designs included case reports (n=52), case series (n=22), cross-sectional (n=22), case-control (n=14), and cohort studies (n=12). Pruritus frequently appeared early or as a sole feature, especially in non-bullous variants. Mechanistic studies highlighted roles for eosinophils, IgE, IL-4/IL-13, and IL-31 in BP-associated itch. Anti-BP180 titers correlated with itch severity. Validated itch or quality of life instruments were used in 54 studies (e.g. BPDAI, VAS, DLQI), though measurement methods were inconsistent. Some studies reported improvement with therapies targeting IgE or IL-4/IL-13 pathways. Notably, itch was reported as a significant concern in select pemphigus subtypes, where further investigation is warranted. Conclusion: Pruritus in AIBDs is common, clinically meaningful, and mechanistically complex. Targeted therapies and standardized measurement tools represent promising directions for future research.
P139
Title:
Association
between pruritus and social isolation: a cross-sectional study
Submitting
author:
Goto, Kazuya - Kyoto University Graduate School of
Medicine, Department of Dermatology, 54 Shogoin-Kawahara-cho,
Sakyo-ku, Kyoto 606-8507, Japan
Abstract:
Background: Patients who experience itch may be misunderstood by people around them as having an infectious disease due to their scratching behavior in public, potentially leading to social isolation. Recent studies have reported the association between social isolation and lower healthcare-related quality of life, the increased risk of all-cause mortality, cerebrovascular and cardiovascular diseases, and dementia. However, the association between pruritus and social isolation remains unclear. Objective: To investigate the association between pruritus and social isolation using a web-based survey of a representative sample of the Japanese general population. Methods: We conducted a cross-sectional study using data from the May 2024 survey of the Quality of Life in COVID-19 Era (QoLCoVE) study. Participants were selected using quota sampling based on the recent census data. The primary exposure was pruritus. Participants were classified into pruritus-present and pruritus-absent groups for comparison, based on pruritus intensity assessed with a five-point Likert scale. The primary outcome was social isolation, defined as a score below 12 on the Japanese version of the abbreviated Lubben Social Network Scale (LSNS-6). Modified Poisson regression was used to estimate adjusted risk ratios (aRRs) and 95% confidence intervals (CIs), adjusting for potential confounders. Results: Data analysis is currently ongoing. Conclusion: Pruritus may be associated with social isolation. Appropriate interventions for pruritus could reduce the risk of social isolation and, in turn, inprove the HRQoL and prevent related adverse health outcomes.
P140
Title:
Mu
Opioid recepor antagonists as novel antiprutiic agents for refractory
itch
Submitting
author:
Ho, Bernard - St George's University Hospitals NHS
Foundation Trust
Abstract:
Chronic idiopathic pruritus and nodular prurigo are common dermatological conditions that can be challenging to treat and may cause significant psychological distress. Current treatments, which include emollients, topical steroids, phototherapy, antihistamines, antidepressants, and immunosuppressants, often yield disappointing results or lead to undesirable side effects.
Naloxegol and naldemidine are peripherally acting µ- opioid receptor antagonists used to treat opioid-induced constipation. They inhibit the itch pathway by blocking the opioid receptors involved in itch signaling, showing potential as therapies for chronic pruritus in patients unresponsive to other treatments. We present a case series of five patients treated with opioid antagonists, naloxegol or naldemidine.
The five patients all had treatment-resistant pruritus, three with idiopathic chronic pruritus and two with nodular prurigo, treated off-label with µ-opioid receptor antagonists (either naloxegol or naldemidine) with varying success. The patients were aged between 26 and 79 years and all had failed treatment with topical steroid therapy; two had previously received treatment with oral corticosteroids while two had undergone phototherapy with little improvement. All five patients were started on naloxegol at a dose of 25 milligrams once daily. Due to local supply issues, three patients were switched to naldemidine at a dose of 200 micrograms once daily.
Noticeable improvement in symptoms was observed in three patients, with an average reduction in itch severity of 4-4.5 on the visual analogue scale. Complete resolution of symptoms occurred in one patient, with the Dermatology Life Quality Index score dropping from 19 to 1 after eight months of treatment. One patient reported no improvement in symptoms but had intermittent adherence due to local supply issues. Only one patient experienced mild gastrointestinal side effects immediately after commencing therapy; however, they continued treatment, and these side effects subsided shortly after.
These results suggest that peripheral µ-opioid receptor antagonists have potential as effective treatment options for chronic pruritus; however, further studies are needed to confirm their efficacy.
P141
Title:
Association
Between Atopic Dermatitis and Dupilumab-Induced Conjunctivitis Among
Patients with Prurigo Nodularis
Submitting
author:
Krajewski, Piotr - Department of Dermatology,
Venereology and Allergology, Wroclaw Medical University
Abstract:
Background: Conjunctivitis is recognized as the most common ocular adverse event associated with dupilumab treatment, especially in patients with prurigo nodularis (PN). Despite this, the specific risk factors that might make PN patients more susceptible to developing conjunctivitis from dupilumab are not well understood. This study explores whether the presence of atopic dermatitis (AD), which often occurs alongside PN, affects the likelihood of developing dupilumab-induced conjunctivitis. Methods: Using data from the TriNetX Global Collaborative Network, which includes 147 healthcare organizations, we identified adult patients with PN who were receiving dupilumab treatment. Patients were categorized into two groups: those with PN and concomitant AD, and those with PN only. Patients with a history of conjunctivitis were excluded. Propensity score matching was used. We analyzed first-onset conjunctivitis by calculating risk difference (RD), risk ratio (RR), and hazard ratios (HR) using Kaplan-Meier analysis. Results:. Dupilumab-related conjunctivitis was significantly more common in patients with PN and concurrent AD (4.1%) compared to those without AD (1.2%), with a risk difference (RD) of 2.9% and a relative risk (RR) of 3.45 (95% CI: 2.17-5.49). Kaplan-Meier analysis showed a higher hazard of conjunctivitis in PN patients with AD (HR 2.26; 95% CI: 1.41-3.63, p=0.001). The Cox regression model identified AD as an independent risk factor (HR 1.33; 95% CI: 1.23-1.44, p<0.001), along with allergic rhinitis (HR 2.15) and asthma (HR 1.55). Male sex was associated with a reduced risk (HR 0.85). Conclusions: Concomitant atopic dermatitis significantly increases the risk (3.5 times higher) and hazard (2.3 times higher) of dupilumab-related conjunctivitis in patients with prurigo nodularis. Due to this increased risk, baseline ophthalmologic assessments and proactive ocular-surface management are recommended for PN patients starting dupilumab treatment, especially those with existing AD.
P142
Title:
MANAGING
THE ATOPIC TRIAD: AN EDUCATIONAL INTERVENTION FOR PARENTS IN
UNDERSERVED COMMUNITIES
Submitting
author:
Kunta, Niharika - School of Medicine, Baylor College of
Medicine, 1 Baylor Plaza, Houston, TX, USA
Additional
Authors:
Anjali Aggarwal, M.D., FAAFP Department of Family and
Community Medicine, Baylor College of Medicine, 1 Baylor Plaza,
Houston, TX, USA
Abstract:
Introduction: Despite the increasing burden of eczema globally2, many parents may struggle with managing atopic conditions (AC). Lower health literacy can contribute to resistance in using topical corticosteroids for the management of eczema2 and increased fears of steroids can contribute to treatment failure and flare ups1. One method of improving outcomes can be through educational interventions. Objectives: The objectives are to provide resources that improve knowledge and confidence in managing AC for parents in underserved communities with information on treatments including topicals and wet wraps. Methods: The study consists of a survey administered before and after a presentation given at local health and back-to-school fairs in underserved communities. Participants were voluntarily recruited and included English-speaking adults with children who have AC. Participants answered questions regarding their knowledge about and confidence in managing AC on a scale of 0 to 4. Results: There were a total of 16 participants and the most common condition among their children was eczema (n=12). The majority of children with eczema also had seasonal allergies, with a total of 11. Asthma was the least common with only 3 children having it. The average survey score for eczema before the presentation was 2.6 and increased to 3.9 after the presentation, with a p-value of 0.0299. For asthma, the average score before was 3.5 and increased slightly to 3.7 after, with a p-value of 0.3014. With allergies, the scores before and after were 2.5 and 3.8, respectively, with a p-value of 0.0140. Conclusion: This educational intervention overall improved parents’ understanding of AC and confidence in managing them, especially for eczema and allergies which showed a statistically significant difference in survey scores before and after. However, the small sample size and variability in presentations severely limits these findings.
P143
Title:
Characteristics
of chronic kidney disease-associated pruritus: psychosocial factors
interact with pruritus to impair the quality of life
Submitting
author:
Kupper, Cecil Catherine - University Hospital Münster,
Department of Dermatology, Von-Esmarch Straße 58, 48149 Münster
Additional
Authors:
Kupper C., Zeidler C., Ständer S., Brand M
Abstract:
Introduction
Chronic kidney disease-associated pruritus (CKD-aP) significantly impairs the patients´ quality of life. This study aimed to further characterize CKD-aP in terms of severity, variability, and its modulation by hemodialysis, as well as to explore alternative methods for alleviation of symptoms other than medications.
Methods
Fifty patients (≥ 18 years) on chronic hemodialysis with CKD-aP for a minimal duration of 6 weeks were recruited. Several questionnaires assessed pruritus characteristics and quality of life. Additionally, a qualitative interview explored the patient`s perspective regarding disease burden and individually developed measures for pruritus deflection. Data were analyzed using SPSS (version 29.0.2.0).
Results
From March 2023 – June 2024, fifty patients were recruited, thirty-four patients were questioned twice (June – August 2024). The median age was 59 years. Pruritus intensity ranged widely, with 42% of the patients presenting with mild to moderate pruritus (NRS < 4). Mostly the trunk and limbs were affected. No significant relation between duration of hemodialysis and pruritus intensity or distribution was found. However, hemodialysis was a general risk factor for pruritus occurrence (p = 0.017). Pruritus intensity correlated with quality of life impairment, yet multivariate regression analysis revealed additional contributing factors. Patients reported multiple symptoms that interact and amplify the overall disease burden, including impaired sleep, mood deterioration, and concentration difficulties. Situation-related deflection of pruritus was possible for 52.9% of patients through social interaction and skill-based activities. Reduction of scratching in social environments was reported by 64.7% of the patients. Rapid-acting, on-demand medication (pills/infusion) were preferred over previously prescribed topical agents.
Conclusion
CKD-aP is multifaceted and presents with no clear relation between hemodialysis and disease severity. Quality of life is influenced by pruritus combined with other psychosocial factors suggesting the need of non-pharmacological therapies. Moreover, patient-centered treatment approaches to ensure adherence to treatment should be further investigated.
P144
Title:
Multidirectional
relationship between Chronic Pruritus, Attention-Deficit/
Hyperactivity Disorder, and Skin Picking Disorder
Submitting
author:
Loos, Eva - University Hospital Basel, Department of
Dermatology, Petersgraben 4, 4031 Basel, Switzerland
Abstract:
Chronic pruritus (CP), attention-deficit/hyperactivity disorder (ADHD), and skin picking dis-order (SPD) are medical conditions that involve both somatic and psychosocial dimensions, posing unique challenges in clinical management. While CP and SPD are often observed to-gether, the link between ADHD and these conditions is less recognized. Based on clinical observations in three women treated at our specialized psychodermatological pruritus clinic, we assume a bidirectional, triangular relationship between CP, ADHD, and SPD. To support this assumption, we propose two hypotheses: (1) a neurodevelopmental hypothesis, emphasiz-ing that ADHD as an underlying neurodevelopmental disorder, might present with symptoms like dysfunction of sensory processing, impulsivity, and attention deficits as shared features that reinforce CP and SPD, and (2) a neuroinflammatory hypothesis, suggesting that similar neuroinflammatory signatures promote the co-occurrence of CP, ADHD, and SPD. Elucidat-ing the interplay between these three conditions might help develop personalized treatment strategies and improve outcomes.
P145
Title:
Virtually
Connected, Physically Affected? Itch Contagion in Human–Virtual
Character Relationships
Submitting
author:
Mattens, Jard - Department of Dermatology, Amsterdam
Institute for Infection and Immunity, Amsterdam UMC, Amsterdam, The
Netherlands | Health, Medical, and Neuropsychology Unit, Faculty of
Social and Behavioural Sciences, Leiden University, Leiden, the
Netherlands
Additional
Authors:
Antoinette I.M. van Laarhoven,*1, J.D.J. Mattens,1,2*,
T.F. Wilderjans,4, R. Sellaro,**3, Mariska E. Kret,**4 1 Health,
Medical, and Neuropsychology Unit, Faculty of Social and Behavioural
Sciences, Leiden University, Leiden, the Netherlands 2 Department of
Dermatology, Amsterdam Institute for Infection and Immunity,
Amsterdam UMC, Amsterdam, The Netherlands 3 Department of
Developmental Psychology and Socialisation, University of Padua,
Padua, Italy 4 Cognitive Psychology Unit, Faculty of Social and
Behavioural Sciences, Leiden University, Leiden, the Netherlands *
Joint first authorship ** Joint last authorship
Abstract:
Introduction: Contagious itch—triggered by observing or hearing about itch or scratching—has been reported in humans, apes, and rodents. It is thought to serve an adaptive function by priming immune responses to potential parasitic threats. In rodents, the effect seems socially modulated; in humans, social components remain less understood. Objectives: This study investigated whether virtual characters (VCs) differentially displaying scratching behaviour alongside itch-related or neutral pictures could elicit scratching in humans. Methods: A within-subjects design was used with 41 participants (10 males; median age=21 years, IQR=20-23 years, age range=18–35 years) completing 96 trials of a picture description task (itch-related or neutral) with or without an accompanying - scratching or non-scratching – virtual character. After each block, participants rated amongst others itch and urge to scratch. Results: Participants scratched a median of 6 times (IQR=4-14) across all 96 trials (with 24 VC scratches) with a median total duration of 21.2 s (IQR=12.0-43.6 s). Three participants never scratched, while the most active scratched up to 46 times. Scratching occurred primarily on the face (29.5%), legs (25.7%), and hand (17.9%). Scratch frequency and duration did not differ significantly across conditions (p>.05). The number of participant scratches was overall low compared to the number of VC-scratches (1:4). Conclusion: Virtual characters’ scratching did not significantly induce more contagious scratching compared to non-scratching behaviour. Effects may have been masked, amongst others by carryover effects and behavioural inhibition by physical sensors attached to the participants. More research is needed to elucidate the role of social factors in establishing contagious itch, and conversely the role of contagious itch in social bonding.
P146
Title:
Can itch
contagion be learned? An experimental study on classical conditioning
of auditory itch
Submitting
author:
Meeuwis, Stefanie - Department of Medical and Clinical
Psychology, Tilburg University, Tilburg, The Netherlands; Health,
Medical and Neuropsychology Unit, Institute of Psychology, Faculty of
Social and Behavioural Sciences, Leiden University, Leiden, The
Netherlands
Additional
Authors:
Henning Holle; Institute of Psychology, University of
Hull, Hull, United Kingdom
Abstract:
Introduction. Placebo and nocebo effects can affect cutaneous itch intensity via expectations and classical conditioning. It is not yet clear whether similar learning processes are involved in the emergence and aggravation of contagious itch. Objectives. The current study investigates whether contagious itch can be classically conditioned using an experimental paradigm, in which itch-evoking audiovisual stimuli are paired with visual cues (conditioned stimuli; CSs. In addition, it is tested whether conditioned itch is stronger when negatively valenced cues are used, compared with neutral cues. Methods. In a mixed study design, participants are randomized to 1) a negative valence-group (CSs of an aversive facial expression) or 2) a neutral-group (CSs of neutral facial expressions). In the learning phase of the conditioning paradigm, scratching sounds (UCS) are paired with a conditioned stimulus (CS+; picture of a face). As positive control, rubbing sounds are paired with a CS- (picture of a different face). Subsequently during evocation, both CS+ and CS- are paired with rubbing sounds. Results. Data collection is still ongoing. An initial analysis of a pilot sample (n = 34; Mage±SD = 20.3±1.6, 85.3% female) demonstrated a significant interaction between CS type and phase (p = .006). A main effect of group was also found, with participants in the negative valence-group reporting higher overall itch relative to the neutral-group (p = .015). A marginal non-significant difference between CS+ and CS- was noticed in the testing phase for the negative valence-group exclusively (p = .083). Conclusion. These pilot findings may indicate that contagious itch is conditioned more easily when associated with negatively valenced cues but need to be replicated in a larger sample. Demonstrating the involvement of learning processes in contagious itch could provide input for conceptual frameworks detailing the mechanisms of this phenomenon.
P148
Title:
Perceived
stress in patients with chronic pruritus
Submitting
author:
Royeck, Svenja - Section for Pruritus Medicine,
Department of Dermatology, Center for Chronic Pruritus (KCP),
University Hospital Münster, Von-Esmarch-Str. 58, 48149 Münster,
Germany
Abstract:
Introduction & Objectives: Chronic pruritus (CP; ≥6 weeks) is a burdensome persistent somatic symptom in chronic prurigo (CPG), atopic dermatitis (AD), and non-lesional skin (CPNL) involving complex biological and psychological interactions. While perceived stress exacerbates pruritus intensity across dermatoses, its role in CP persistence remains poorly defined. This study systematically evaluated perceived stress in AD, CPNL and CPG patients. Materials & Methods: Our prospective cohort study enrolled eligible CP patients ≥18 years from a tertiary centre. Participants underwent structural interviews characterizing pruritus-associated stress. Assessments included Worst Pruritus Numerical Rating Scale (WP-NRS; 0–10), Perceived Stress Scale (PSS-10; 0–40) and Perceived Stress Questionnaire (PSQ-30; 0–1). Statistical methods comprised descriptive analyses, Kruskal-Wallis tests (group comparisons), and Spearman's correlations. Results: Data from 31 adults with CP were analysed (mean age 51.0±15.6 years; 51.6% female). WP-NRS was moderate (5.8±2.9); stress levels were elevated. Qualitative interviews revealed consistent stress-induced manifestations (93.5% reported intensified scratching behaviour, 71.0% increased irritability/conflict susceptibility, 67.7% stress-triggered pruritus exacerbations). 4/10 PSS-10 items demonstrated high impact for pruritus-related stress. Inter-group comparisons revealed no significant differences in perceived stress (Kruskal-Wallis: PSS-10 p=0.41; PSQ-30 p=0.82). Weak, non-significant correlations emerged between perceived stress and pruritus intensity (PSS-10: ρ=0.27, p=0.14; PSQ-30: ρ=0.27, p=0.14). Conclusion: The high frequency of stress-aggravated symptoms necessitates routine stress assessment and targeted interventions. Based on the reported domains associated with pruritus-associated stress, we framed a novel questionnaire. Currently, 240 patients are recruited to determine construct validity. This questionnaire will help analyzing biological and psychological stress mediators, elucidating their contribution to CP persistence.
P149
Title:
Perceived
stress in patients with chronic pruritus
Submitting
author:
Royeck, Svenja - Section for Pruritus Medicine,
Department of Dermatology, Center for Chronic Pruritus (KCP),
University Hospital Münster, Von-Esmarch-Str. 58, 48149 Münster,
Germany
Additional
Authors:
Svenja ROYECK (1); Johanna PAPATHANASSIOU (1); Angelika
WEIGEL (2); Nell KINDT (2); Bernd LÖWE (2); Christian MESS (3);
Claudia ZEIDLER (1); Felix WITTE (1); Konstantin AGELOPOULOS (1);
Henning WIEGMANN (1); Stefan W. SCHNEIDER (2); Sonja STÄNDER (1)
1Department of Dermatology and Center for Chronic Pruritus (KCP),
University Hospital Münster, Münster, Germany 2Department of
Psychosomatic Medicine and Psychotherapy, University Medical Centre
Hamburg-Eppendorf, Hamburg, Germany 3Department of Dermatology and
Venereology, University Medical Center Hamburg-Eppendorf (UKE),
Hamburg, Germany
Abstract:
Introduction & Objectives: Chronic pruritus (CP; ≥6 weeks) is a burdensome and persistent somatic symptom in chronic prurigo (CPG), atopic dermatitis (AD), and non-lesional skin (CPNL) involving complex biological and psychological interactions. While perceived stress exacerbates pruritus intensity across dermatoses, its role in CP persistence remains poorly defined. This study systematically evaluated perceived stress in AD, CPNL and CPG patients. Materials & Methods: Our prospective cohort study enrolled eligible CP patients ≥18 years from a tertiary centre. Participants underwent structural interviews characterizing pruritus-associated stress. Assessments included Worst Pruritus Numerical Rating Scale (WP-NRS; 0–10), Perceived Stress Scale (PSS-10; 0–40) and Perceived Stress Questionnaire (PSQ-30; 0–1). Statistical methods comprised Kruskal-Wallis tests (group comparisons), and Spearman's correlations. Results: Data from 31 adults with CP were analysed (mean age 51.0±15.6 years; 51.6% female; subgroups: n=11 AD, n=10 CPG, n=10 CPNL). WP-NRS was moderate (5.8±2.9); stress levels were elevated (PSS-10: 17.7±7.3; PSQ-30: 0.42±0.19). Qualitative interviews revealed consistent stress-induced manifestations as 93.5% reported intensified scratching behaviour, 71.0% described increased irritability/conflict susceptibility and 67.7% noted stress-triggered pruritus exacerbations. 4/10 PSS-10 items demonstrated high impact for pruritus-related stress. Inter-group comparisons revealed no significant differences in perceived stress (Kruskal-Wallis: PSS-10 p=0.41; PSQ-30 p=0.82). Weak, non-significant correlations emerged between perceived stress and pruritus intensity (PSS-10: ρ=0.27, p=0.14; PSQ-30: ρ=0.27, p=0.14). Conclusion: Perceived stress is prevalent in CP and frequently amplifies symptom burden. Despite absent inter-group differences or stress-pruritus correlations, the high frequency of stress-aggravated symptoms necessitates routine stress assessment and targeted interventions. Based on the reported domains associated with pruritus-associated stress, we framed a novel questionnaire. Currently, 240 patients are recruited to determine construct validity.
P151
Title:
Contagious
itch: What triggers the urge and in whom?
Submitting
author:
van Laarhoven, Antoinette I.M. - Institute of
Psychology, Health, Medical and Neuropsychology Unit, Leiden
University, Leiden, the Netherlands
Additional
Authors:
Dr. H. Holle, Department of Psychology, University of
Hull, Hull, UK. Dr. D.M.W. Balak, Department of Dermatology, Leiden
University Medical Center, Leiden, The Netherlands Dr. S. van Beugen,
Institute of Psychology, Health, Medical and Neuropsychology Unit,
Leiden University, the Netherlands
Abstract:
Contagious itch refers to the experience of itch triggered by observing itch-related cues in the environment, such as others scratching or discussing itch. This response likely has evolutionary roots, aiding in parasite avoidance. Research shows that individuals with chronic itch are more susceptible, potentially exacerbating their symptom burden. Traits like empathy and self-consciousness have also been associated with increased susceptibility. More recently, contagious itch has been associated with the behavioral immune system (BIS), which promotes avoidance of potential pathogens. However, few studies have systematically examined which specific cues most effectively trigger itch contagion. This study investigated how different triggers, i.e., a visible skin condition, scratching, and itch-related talking, affect contagious itch, and how individual differences contribute to susceptibility. A total of 378 adults completed an online survey, viewing video vignettes of various itch-related scenarios. Participants rated their perceived itch and urge to scratch, as well as their desire for social avoidance of the person depicted (reflecting stigmatizing attitudes). They also completed self-report measures, including the Self-Consciousness Scale, the Interpersonal Reactivity Index (empathy), and the Pathogen Disgust subscale of the Three Domains of Disgust Scale (BIS sensitivity). Results showed that contagious itch was most strongly triggered by visible skin conditions combined with either scratching or itch-related talk. However, combining scratching and talk did not further intensify the response. Individuals more susceptible to contagious itch scored higher on self-consciousness, empathy, and pathogen disgust sensitivity. Visibility of the skin condition in particular evoked significant social distancing responses. These results highlight the key role of social and visual cues in contagious itch and suggest a saturation effect when multiple cues are combined. A follow-up study is currently underway to experimentally test the causal role of BIS in this phenomenon.
P152
Title:
Chronic
stress characteristics of patients with chronic prurigo: results of
an interview study
Submitting
author:
Waitek, Maurice - Division of Occupational Dermatology,
Department of Dermatology, University Hospital Heidelberg,
Heidelberg, Germany
Additional
Authors:
Elke Weisshaar, MD, PhD/Division of Occupational
Dermatology, Department of Dermatology, University Hospital
Heidelberg, Heidelberg, Germany
Abstract:
Chronic Prurigo (CPG) is „a distinct disease defined by the presence of chronic pruritus and multiple localized or generalized pruriginous lesions“. It is known that CPG can often be of multifactorial origin with psychological factors playing an important role, especially stress. We have observed significant chronic stressors in CPG patients. However, there are limited studies on the role of stress in CPG. We conducted qualitative interviews to investigate the characteristics of psychological stress in CPG patients. So far, six interviews have been conducted. The interviews took 20-60 minutes. The interview comprised 17 questions about e.g. what patients perceive as stressful, in what situations they experience it or how they cope with stress. Time pressure and having to deal with too many things at once were reported as stressful situations as well as feeling constrained by the disease itself, but also by external factors. Pruritus was also reported as stressful and highly burdensome with two patients perceiving an influence of stress on their pruritus. The patients attributed stress to work (e.g. conflicts with colleagues) or private conditions such as household tasks and family members. Patients felt resistant to stress, but that the disease still inflicted significant burden. Patients reported to cope with stress by doing leisure activities such as sports, hobbies, relaxation exercises and said to have developed these ways of coping due to necessity. According to our interview study, CPG patients seem to suffer from several external (e.g. working conditions, personal relations) and internal (e.g. CPG, perfectionism) chronic stressors. We conclude that chronic stress is a major problem in CPG patients. Stress should be systematically investigated in CPG in the future.
P153
Title:
Emerging
treatments of chronic pruritus in the elderly
Submitting
author:
Waitek, Maurice - Division of Occupational Dermatology,
Department of Dermatology, University Hospital Heidelberg,
Heidelberg, Germany
Additional
Authors:
Elke Weisshaar, MD, PhD/Division of Occupational
Dermatology, Department of Dermatology, University Hospital
Heidelberg, Heidelberg, Germany
Abstract:
Chronic pruritus (CP) in the elderly is a complex and growing problem, especially in Western countries. The treatment of CP in this age group is challenging. Pathophysiological changes of ageing skin like e.g. xerosis cutis, systemic diseases, comorbidities and polypharmacy are common in this age group. Further, pharmacokinetics in the elderly is different (e.g. reduced renal function, decreased specific immunological responses). A number of new antipruritic therapies have been approved recently. However, these drugs have not been approved in elderly patient populations, because most studies have age limits of 75 or 80 years. The biologic dupilumab has shown good efficacy in CPG according to case reports and series. Nemolizumab, another biologic therapy, was efficacious in Japanese CPG patients with an age range of 13-84 years across the different dosages median age of 75, but the population was not strictly focused on elderly patients. Looking at CP in Atopic Dermatitis (AD), tralokinumab showed a higher drug survival rate in over 60 year olds compared to under 60 year olds after 18 months. In AD patients 65 years and older, dupilumab reduced the pruritus intensity by 71.91% at week 16. The Janus-Kinase (JAK) inhibitors abrocitinib, baricitinib and upadacitinib significantly reduced the peak pruritus intensity. All these studies reported good safety profiles, but comorbidities and interfering medications of real-life elderly patients may influence and make the use of systemic agents less safe. In general, topical treatments might be more safe in the elderly. According to a Korean study, asivatrep, a topical transient receptor potential vanilloid 1 (TRPV1) antagonist, may be beneficial for elderly patients suffering from age-related pruritus. Other new treatments for CP like e.g. the topical JAK-inhibitor ruxolitinib have not been sufficiently investigated in elderly patient populations, but could be used even in combination with other topical therapies or emollients. In summary, more studies on antipruritic treatments in the elderly are needed, also considering a combination of treatments like topical and systemic treatments.
P154
Title:
Semaglutide
as a possible treatment for Darier's disease? - A case report
Submitting
author:
Böhm, Maximilian - Department of Dermatology,
University Hospital of Basel, Burgfelderstrasse 101, 4055 Basel,
Switzerland
Additional
Authors:
M. Böhm ¹ E. Contassot ¹ ² B. Winzeler ³ A.
Navarini ¹ S. Müller ¹ ¹ Department of Dermatology, University
Hospital of Basel, Switzerland ² Department of Biomedicine,
University Hospital and University of Basel, Switzerland ³
Department of Endocrinology, Diabetology and Clinical Nutrition,
University Hospital of Zurich, Switzerland
Abstract:
Darier’s disease (DD) is a dyskeratotic and acantholytic genodermatosis characterized by persistent keratotic papules and plaques. Typically, DD causes severe chronic itch and significantly impacts quality of life. Therapeutic options are limited and primarily symptomatic, including topical corticosteroids, antiseptics and the avoidance of triggers. Systemic retinoids are considered effective, but side effects may restrict long term use. Here, we present the case of a 37-year-old female patient with previously treatment refractory DD showing an excellent response of itch ratings and an improvement of skin status after initiating obesity treatment with the glucagon-like peptide-1 receptor agonist semaglutide. Prior to starting semaglutide, the patient had shown a poor response to topical treatments (corticosteroids, retinoids, antiseptics, among others), antihistamines and immunoglobulins. Systemic retinoids were not initiated due to ongoing family planning and dyslipidemia. NanoString nCounter® analysis of lesional skin prior to semaglutide revealed a high mRNA expression of Interleukin-1β, Interleukin-17A and Interleukin-22. After two months of treatment and clinical improvement of skin status and itch, Interleukin-17A was significantly downregulated, while Interleukin-1β and Interleukin-22 mRNA expression remained high. Interleukin-17A is a key proinflammatory cytokine which promotes itch, keratinocyte proliferation and altered keratinocyte differentiation. Topical treatments had remained unchanged, making semaglutide the most likely driver of the change in the inflammatory response. Therefore, Semaglutide may be a promising new treatment for DD through the downregulation of Interleukin-17A.
P155
Title:
Evidences
for gestures associated with pruritus in very young infants: A pilot
study
Submitting
author:
Boyard, Adrien - Brest University Hospital, Department
of Dermatology, Brest, France.
Laboratory Interactions Neurones-Keratinocytes (LINK), University of Brest, Brest, France
Abstract:
Introduction :
The anatomical and functional basis for pruritus is present before birth. However, pruritus is largely underestimated in newborns and is often considered absent in this population because they cannot scratch.
Objectives :
The aim of this study was to analyze behaviors potentially associated with pruritus in infants under 6 months suffering from atopic dermatitis (AD).
Methods :
Infants under 6 months of age were enrolled in two arms: a healthy group and a group with moderate or severe AD. The severity of AD was calculated using the SCORing Atopic Dermatitis (SCORAD). The infants were videotaped for at least 5 minutes and the videos were analysed by ethologists using the scan-sampling method.
Results:
Thirty-four infants aged 2.5 to 5.5 months were included : 9 healthy infants and 25 infants with AD. Hand movements were more frequent in the AD group than in the healthy infants (p. <0.01). There was no difference between the two groups when hand postures were analysed. Video analysis revealed the presence of self-contact with grasping movements, which could be identified as immature scratching behaviour. This behaviour was statistically more common in the AD group (p=0.03). Correlation analyses showed that this scratching behaviour was associated with SCORAD (p. 0.04), but not with age. There was no association between hand movements and either age or SCORAD.
Conclusions:
This is the first study to highlight behaviours that can be identified in infants with pruritus before they develop the motor capacity to scratch.
P157
Title:
Targeting
the Itch: Clinical Remission of Pruritus in a Case of Folliculotropic
Mycosis Fungoides
Submitting
author:
Chew, Emanuel - Claro, aquí tienes la traducción al
inglés: Mexican Social Security Institute, Department of
Dermatology, Av. Cuauhtémoc 333, Doctores, Cuauhtémoc, 06720 Mexico
City, CDMX
Abstract:
Introduction Folliculotropic mycosis fungoides (FMF) is a rare variant of cutaneous T-cell lymphoma characterized by follicular infiltration and often associated with severe pruritus. Management is challenging due to its chronic, relapsing nature and limited treatment responses. Objectives To report a case of FMF with chronic pruritus and describe the clinical response to combined systemic and topical therapy. Methods A 49-year-old woman with a 14-year history of pruritic lesions underwent multiple lines of treatment. Histopathology and immunohistochemistry confirmed FMF. Previous therapies included PUVA, systemic methotrexate, oral retinoids, and electron beam therapy. On relapse, she was treated with methotrexate, prednisone, and topical clobetasol, pimecrolimus, and imiquimod. Results The patient showed marked clinical improvement following the adjusted treatment regimen. Inflammatory plaques, follicular papules, and tumoral lesions diminished in size and number. Notably, pruritus intensity decreased significantly, improving quality of life. The most recent evaluations documented reduced lesion activity, post-inflammatory pigmentation changes, and improved skin texture, with no signs of secondary infection or systemic progression. Conclusion This case illustrates the potential benefit of combined topical and systemic therapies in folliculotropic MF, including the use of imiquimod as an adjunct. Effective control of pruritus and cutaneous lesions was achieved, underscoring the importance of personalized treatment approaches in managing FMF.
P158
Title:
“The
Itch That Signals More: Unmasking Serum Sickness-like Illness in
Adolescents”
Submitting
author:
Chikhalkar, Gauri - Seth GS Medical College and KEM
hospital, Mumbai,India
Abstract:
Introduction Serum sickness-like illness (SSLI) and autoinflammatory syndromes may present with urticarial wheals mimicking chronic spontaneous urticaria, but their distinct systemic symptoms and immunologic features set them apart. Recognizing such emerging pruritic entities is essential for targeted management and long-term monitoring. Objectives To highlight a potential autoinflammatory urticarial syndrome presenting as serum sickness-like illness in adolescent females, and emphasize its recognition as a distinct clinicopathological entity. Methods We report a case series of three otherwise healthy adolescent females (aged 16–18 years) who presented with recurrent episodes of urticarial wheals for less than 24 hours’ duration, associated with systemic symptoms such as low-grade fever, malaise, and arthralgia. The duration of illness ranged from 6 months to 1 year. Flares were exacerbated by sour food intake. Clinical evaluation and dermoscopy revealed a red dermal hue. Skin biopsy demonstrated eosinophilic infiltrates in the upper dermis, focally around blood vessels. Laboratory workup including complete blood count, renal and liver function tests, ANA, and complement levels (C3, C4) were within normal limits in all patients. Results No autoimmune markers or infectious triggers were identified. The clinical picture suggested a serum sickness-like or autoinflammatory urticarial syndrome. All patients responded well to oral second-generation antihistamines with significant symptom control. No systemic immunosuppression was required. Patients remain stable under dermatologic follow-up. Conclusion This series highlights the importance of recognizing evolving presentations of SSLI or autoinflammatory urticarial syndromes in the adolescent population. While mimicking chronic urticaria, these cases exhibit systemic features without classical autoimmune markers. Prompt recognition, appropriate investigation, and symptomatic management can prevent overtreatment and ensure long-term disease control. Further studies are needed to better define this entity’s pathogenesis and classification.
P159
Title:
When
Itch Signals More: Urticarial Vasculitis Unmasked and Complicated by
Dapsone-Induced Febrile Neutropenia
Submitting
author:
Chikhalkar, Gauri - Seth GS Medical College and KEM
Hospital, Mumbai,India
Additional
Authors:
Dr. Gauri Chikhalkar 3rd year dermatology resident ,
Department of Dermatology, Seth G.S. Medical College and KEM
Hospital, Mumbai, India
Abstract:
Introduction Chronic itch is a diagnostic challenge that may reflect underlying systemic or inflammatory pathology. Urticarial vasculitis (UV), a rare small-vessel vasculitis, presents with recurrent pruritic wheals, often mistaken for chronic spontaneous urticaria. Early recognition is critical, particularly when systemic associations or treatment complications arise. Objectives To highlight urticarial vasculitis as a cause of recurrent itch in a patient with chronic hepatitis B, and to discuss the serious but rare complication of dapsone-induced febrile neutropenia, even in G6PD-normal individuals. Methods A 36-year-old female presented with a 5-month history of transient, intensely pruritic, erythematous wheals over the upper limbs and trunk, associated with burning, low-grade fever, and sleep disturbance. Lesions resolved with hyperpigmentation within days. No signs of angioedema, atopy, or systemic autoimmune disease were noted. Laboratory evaluation revealed active hepatitis B (HBsAg+, elevated HBV DNA) but normal complement levels and negative ANA/dsDNA. Dermoscopy showed red globules on an orange-brown background. Histopathology confirmed urticarial vasculitis with perivascular neutrophilic infiltrates and RBC extravasation. The patient was initiated on dapsone, hydroxyzine, and levocetirizine. Results Although lesions partially improved, the patient developed malaise and low-grade fever by day 15 of dapsone therapy. Bloodwork confirmed febrile neutropenia. Dapsone was immediately discontinued, and the patient was treated with G-CSF and broad-spectrum antibiotics. Her hematologic parameters normalized within a week. No infectious source was identified. Conclusion This case underscores the need to consider urticarial vasculitis in patients with recurrent itch unresponsive to antihistamines. While dapsone remains a therapeutic option, clinicians must remain vigilant for idiosyncratic hematologic complications—even in G6PD-normal patients. Routine monitoring and early recognition of neutropenic symptoms are essential to prevent life-threatening outcomes.
P160
Title:
Unfinished
Stories: Consequences of Melanoma Clinical Trial Discontinuation and
Non-Publication
Submitting
author:
Hafez, Hadeer - Faculty of medicine, October 6th
university, Giza, Egypt.
Additional
Authors:
Abdelrahman Hagag1, Mohamed Ashraf Mohamed2, Mohamed
Saad Rakab3, Ismail Zakaria Ismail2, Aya Jamal Elkenani3, Nada
Elmetwally Ahmed1, Abdelrahman M. Hafez4, Doaa Mashaly1, Ali Tarek
Lasheen2, Mohamed Abdelsalam2. 1Faculty of medicine, October 6th
university, Giza, Egypt. 794 2nd dis, October 6th city, Giza, Egypt.
Hadeerhafez0@gmail.com. +201013844863 2Faculty of Medicine, Misr
University for Science and Technology, 6th of October, Egypt 3Faculty
of Medicine, Mansoura University, Mansoura, Egypt 4Faculty of
Medecine, Damietta University, Damietta, Egypt
Abstract:
Background: Melanoma is a major cause of skin cancer-related death, and clinical trials are essential for advancing melanoma treatment options. However, many trials either are teminated prematurly or are never published, eaving critical data unreported. These “unfinished stories”, hinder scientific progress, waste resources, and limit informed clinical decision-making. Therefore, understanding how many and what factors predict unpublished or discontinued melanoma trials is key to improving the transparency of research and advancing best care for patients. Objective: To identify the extent, characteristics, and variables related to Discontinuation and Non-Publication melanoma clinical investigations. Methods: We systematically searched ClinicalTrials.gov for Melanoma studies up to March 1, 2025. Studies completed within the past 24 months were excluded to account for potential delays in the peer review process. Publication status was identified using NCT numbers. Data on participant gender, age, study design, funding source, type of intervention, sample size, and trial location were collected and analyzed. Multiple logistic regression was used to identify factors associated with trial discontinuation or non-publication. All statistical analyses were conducted using Jamovi version 2.6.24. Results: In total, there were 2,144 trials, with 712 (33.2%) published, 1,215 (56.7%) non-published, and 217 (10.1%) unknown. Of the discontinued trials (516, 24.1%), just 59 (11.4%) were published. Non-publication status was noted to be significant among trials of genetic interventions (OR = 0.104, 95% CI: 0.027-0.401, p=0.001), procedural interventions (OR = 0.262, 95% CI: 0.121-0.567, p<0.001), and in a multicenter trial (OR = 0.185, 95% CI: 0.123-0.278, p<0.001). Also, a study was considerably more probable to be discontinuation if smaller-sized (≤500 participants, p<0.001) or earlier (Phase 1/2, p<0.001). Conclusions: The high frequency of Discontinuation and Non-Publication trials record highlights the importance of efforts toward completing and/or fully publication melanoma clinical investigations, particularly those for genetic and/or procedural treatments and/or smaller tri
P161
Title:
Geriatric
Pruritus Unmasked: Dual Diagnosis of Scabies and Paraneoplastic Itch
Submitting
author:
Kilgin, Hilmi - Istanbul University Cerrahpasa,
Cerrahpasa Faculty of Medicine, Department of Dermatology and
Venereology
Abstract:
Introduction Chronic generalized pruritus in geriatric patients presents a diagnostic challenge due to diverse etiologies, including xerosis, infections, systemic diseases, medications, and malignancies. Scabies is often overlooked in this population owing to atypical signs and diagnostic complexity. Paraneoplastic itch (PI), a systemic reaction to malignancy independent of tumor location or therapy, may precede the cancer diagnosis and typically worsens with disease progression. Objectives To present a geriatric case of generalized pruritus with concomitant scabies (involving the scalp and soles, diagnosed only via UV dermoscopy) and underlying non-Hodgkin lymphoma, highlighting diagnostic and management strategies. Methods A 74-year-old female patient presented with six months of severe generalized pruritus experienced throughout the day. The Dermatology Life Quality Index (DLQI) score was 18, with pruritus intensity rated 8/10 on the Visual Analog Scale (VAS) and 9/10 on the Numerical Rating Scale (NRS). Physical examination revealed xerosis and excoriated lesions on the scalp and soles, sparing the fingerwebs. A diagnostic workup included dermoscopy with UV light, skin scraping, medication review, and systemic evaluation, including malignancy screening. Results UV dermoscopy revealed the ‘ball sign,’ confirming scabies that was not visible on routine examination or microscopy. Non-Hodgkin lymphoma was diagnosed concurrently, likely contributing to the paraneoplastic itch. Treatment with 5% permethrin topical cream, alongside hemato-oncologic therapy, led to significant improvement in both symptoms and quality of life. Conclusion In geriatric patients, generalized pruritus necessitates a comprehensive evaluation of both dermatologic and systemic causes, including paraneoplastic itch. Given its strong association with malignancy, potential risk factors for paraneoplastic itch should be thoroughly investigated. Atypical presentations of scabies require meticulous head-to-toe examination, supplemented by UV dermoscopy.
P162
Title:
A case
of darier disease with onset in advanced age
Submitting
author:
Öner, Şebnem - University of Health Sciences, Izmir
Tepecik Training and Research Hospital, Department of Dermatology and
Venereology, Izmir/Turkey
Abstract:
Darier disease (keratosis follicularis) is a rare genodermatoses with autosomal dominant inheritance. Mutations in the ATP2A2 gene result in impaired intercellular adhesion of epidermal cells. Clinically, it is characterized by itchy, hyperkeratotic papules that begin in sebaceous areas. The diagnosis is supported by typical histopathological findings. A 46-year-old male patient with epilepsy presented to the dermatology outpatient clinic with itchy, scaly papules on the scalp, forehead, ears, nose, neck, and anterior trunk that had been presented for approximately 2 months. Dermatological examination revealed scaly and hyperkeratotic papules located in sebaceous areas. Two punch biopsies were taken from behind the ear and the front of the trunk, According to biopsy result and clinical findings, the patient was diagnosed with Darier disease. Treatment was initiated with systemic acitretin 25 mg/day, topical emollients, moderate-potency topical corticosteroids and topical fusidic acid. The patient was placed under close observation. Darier disease appears especially in the second or third decade. Because it’s seen rarely in older ages, we found it appropriate to contribute our 46-year-old case to the literature.
P163
Title:
Targeted
Autologous Serum Therapy in Chronic Spontaneous Urticaria: A
Biomarker-Linked, ASST-Stratified Prospective Case Series
Submitting
author:
Rathi, Parth - Department of Dermatology, VMMC &
Safdarjung Hospital, New Delhi, India.
Abstract:
Background: Chronic Spontaneous Urticaria (CSU) is a burdensome condition with significant quality-of-life impairment and limited access to biologics in many settings. The Autologous Serum Skin Test (ASST) can identify autoimmune endotypes of CSU, and Autologous Serum Therapy (AST) offers a promising, low-cost immunomodulatory treatment. Objective biomarkers such as D-dimer and IgE may enhance personalized disease monitoring. Objective: To evaluate the clinical and biomarker response to AST in ASST-positive CSU patients, using ASST as a stratification tool and D-dimer/IgE as potential markers of treatment response. Methods: In this prospective case series (n = 40), adult CSU patients underwent ASST. ASST-positive patients (n = 22) received weekly AST injections for 8 weeks. ASST-negative patients (n = 18) were monitored without intervention. Clinical outcomes included Urticaria Activity Score (UAS7), Dermatology Life Quality Index (DLQI), and antihistamine burden. Serum D-dimer and total IgE were measured pre- and post-treatment. Results: Among ASST-positive patients, mean UAS7 scores declined from 23.1 to 9.2 (p < 0.001), and DLQI improved from 14.5 to 5.1 (p < 0.001). Antihistamine dependence was reduced in 73% of treated patients. Notably, D-dimer and IgE levels showed a statistically significant downward trend, correlating with clinical improvement (Spearman’s ρ = 0.48 and 0.41, respectively). ASST-negative patients demonstrated minimal change in clinical or biomarker metrics. Conclusion: This study highlights ASST as a valuable tool to guide low-cost, effective treatment in autoimmune CSU. AST not only improves symptom burden and quality of life but also shows concordance with objective biomarker changes. In settings where biologics are inaccessible, ASST-guided AST offers a scalable, precision-medicine approach to urticaria care.
P164
Title:
Dual
Diagnosis, Single Solution: Dupilumab in Perforating Dermatosis
coexisting with Bullous Pemphigoid
Submitting
author:
Riegler, Margareta Johanna - Medical University of Graz,
Dermatology, Auenbruggerplatz 8, 8036 Graz
Additional
Authors:
Riegler MJ, Sauseng C, Schadelbauer E, Gruber V, Schirl
C, Legat FJ
Abstract:
Introduction: Acquired perforating dermatosis is a rare skin disease, which presents as umbilicated papules or nodules with central hyperkeratotic material. The disease is characterized by marked pruritus and is often associated with diabetes mellitus, chronic renal insufficiency and hyperuricemia. Objectives: We report a case of a 66-year-old woman with acquired perforating dermatosis (APD) coexisting with bullous pemphigoid (BP) treated at the Department of Dermatology, Medical University of Graz. Methods: The patient presented to our clinic with pronounced itching and skin lesions on the abdomen and back, starting in December 2023. All previous treatments had been insufficient. Examination including lab tests and imaging showed no abnormalities - notably no diabetes, no renal insufficiency or hyperuricemia. However, indirect immunofluorescence revealed IgG deposits on the blister roof in the salt-split skin test, along with increased basement membrane zone antibodies were detected (1:40+), indicating an IgG mediated subepidermal bullous autoimmune dermatosis of the pemphigoid type. Results: Off-label treatment with Dupilumab was initiated, leading to a significant improvement. A significant reduction in pruritus could be detected, showing a decrease in peak pruritus from 7 to 1 point on the numeric rating scale after 6 weeks of treatment. Dupilumab therapy was administered for five months, resulting in complete resolution of the cutaneous lesions. Due to the necessity of subsequent antibiotic therapy for the treatment of gastritis, the treatment was paused and up to now not restarted. To date, there has been no recurrence of the symptoms. Conclusion:This case represents a rare example of APD coexisting with BP. APD can have a variety of underlying causes. Several case reports suggest its concurrent occurrence with BP, raising the question whether this is a distinct variant or 2 seperate entities. No systemic therapy has been approved for APD. However, the use of dupilumab for BP is being investigated, and preliminary findigs suggest its potential as a promising therapeutic option. In addition, several case reports support its potential use in treatment of APD.
P165
Title:
Clinical
Characteristics and Risk Factors for Cutaneous Manifestations
Associated with Nemolizumab in Atopic Dermatitis: A Multicenter
Retrospective Study in Japan
Submitting
author:
Sasaki, Wataru - 日本
Abstract:
Nemolizumab, an anti-interleukin-31 receptor A monoclonal antibody, has been approved in Japan for treating atopic dermatitis (AD)-associated pruritus. While it is effective for itch control, nemolizumab-associated cutaneous adverse events have been increasingly recognized, yet their clinical features remain poorly characterized. In this study, we aimed to investigate the incidence, clinical characteristics, and timing of cutaneous manifestations associated with nemolizumab treatment in patients with AD, and to explore potential associations with baseline disease severity and immunological parameters. We conducted a multicenter retrospective study involving 219 patients aged ≥13 years with AD who received nemolizumab at 13 institutions in Japan between August 2022 and February 2024. Cutaneous eruptions were classified into six categories based on clinical consensus. Patients who received fewer than three doses without developing skin reactions were excluded. Clinical and laboratory parameters were compared between patients with and without cutaneous manifestations. Cutaneous manifestations occurred in 88 patients (40.2%), most commonly within the first three doses. Erythema was the most frequent presentation (69.3%), and 64.3% of eruptions were non-pruritic. No significant associations were observed between the occurrence of skin reactions and baseline eczema area and severity index scores, eosinophil counts, serum immunoglobulin E, or thymus and activation-regulated chemokine levels. Two cases of bullous pemphigoid were identified. Despite topical corticosteroid treatment, nemolizumab therapy was discontinued in 42% of the patients affected. In conclusion, nemolizumab frequently induces early-onset, morphologically distinct cutaneous eruptions that appear to be independent of baseline disease severity or biomarkers.
P166
Title:
Unmasking
Auto aggressive Lepromatous Leprosy: The Great Clinical Chameleon.
Submitting
author:
Sharma, Sunidhi - government medical college and
hospital, chandigarh
Abstract:
Autoaggressive leprosy was first described by Azulay in 1987, though old concept in leprosy can mislead most of the expert dermatologist. As the name suggests it is characterized by clinical and immunologic features resembling autoaggressive connective tissue diseases. Where there’s is stimulation of B lymphocytes by antigenic complexes of Mycobacterium leprae plus autologous tissue along with dysfunction of T-suppressor lymphocytes. We here describe a case of lepromatous leprosy patient who was initially mistaken as acute lupus erythematosus. A 75-year-old female patient presented to us in medicine emergency with a history of high grade febrile episodes, oedema of her feet, arthralgia of the small joints of her hands and feet, photosensitivity, malaise and weakness which had gradually been increasing over a period of 2 months. In addition patient gave history of painful evanescent nodules and blisters over body. Looking at the acuteness of presentation and involvement of face primarily, she was diagnosed as a case of systemic lupus erythematosus initially. But on careful examination and biopsy and split skin smear, a diagnosis of autoaggressive lepromatous leprosy was made. Although various autoantibodies were positive in patient i.e. ANA, rheumatoid factor, and antithyroid antibodies. It has been seen, autoaggressive leprosy encompasses a particular clinical presentation characterized by pro longed fever (37°C-40°C), anorexia, weight loss, asthenia, arthralgia, malar rash, and erythema multiform or necrotizing vasculitis like skin lesions. In addition, one or more autoantibodies are present in the serum of these patients. Our patient had almost all these features for making a diagnosis of autoaggressive lepromatous leprosy. Our case illustrates an unusual presentation of autoaggressive lepromatous leprosy misdiagnosed as systemic lupus erythematosus. It also underscores the importance of careful clinical evaluation when diagnosing conditions with overlapping symptoms, such as leprosy and autoimmune diseases like systemic lupus erythematosus.
P168
Title:
Papular
Mycosis Fungoides with Refractory Pruritus: Successful Control with
Aprepitant
Submitting
author:
Vásconez, Valeria - Universidad Tecnológica
Equinoccial, UTE, Rumipamba y, Bourgeois, Quito 170147, Ecuador
Additional
Authors:
Harvey Pazmiño MD. Head of Dermatology Department at
Hospital Vozandes
Abstract:
Introduction: Pruritus in cutaneous T-cell lymphomas, particularly Mycosis Fungoides (MF), is often a therapeutic challenge and significantly affects quality of life. Papular MF is an extremely rare clinical variant that may delay diagnosis and complicate pruritus management due to its atypical presentation. Objectives: To describe a rare case of papular MF with persistent pruritus resistant to multiple therapies, highlighting the efficacy of aprepitant in symptom control. Case report: A 50-year-old male came for consultation, complaining of generalized, pruritic, erythematous papules, primarily located on the trunk. Initial treatments included corticosteroids, antihistamines, gabapentinoids, and thalidomide, but provided no symptom relief. Multiple biopsies were required to confirm papular MF, supported by histopathology and immunohistochemistry (CD4+ predominance, CD30+ cells, partial CD7 loss). Treatment with narrowband UVB (NB-UVB) phototherapy and methotrexate was initiated. Results: Despite ongoing systemic and phototherapeutic treatments, the patient continued to experience severe pruritus. A trial of aprepitant was initiated (120 mg on the first day and 80 mg on days 2 and 3). This resulted in a rapid and notable reduction in itching, allowing the patient to continue with the existing therapy (NB-UVB + methotrexate). The relief from pruritus persisted even after aprepitant was stopped. No significant side effects were noted. Conclusion: This case highlights the diagnostic difficulty of papular MF and the burden of chronic pruritus. Aprepitant, a neurokinin-1 receptor antagonist, may serve as a valuable off-label option for controlling refractory itch in cutaneous T-cell lymphoma. Early identification of MF variants and personalized symptom-directed therapy, including antipruritic agents such as aprepitant, can significantly improve patient quality of life. Further research is needed to consolidate its role in managing pruritus in MF.
P169
Title:
The Role
of Nasal Hygiene in Refractory Urticaria: Exploring the Mucocutaneous
Connection
Submitting
author:
Vásconez, Valeria - Universidad Tecnológica
Equinoccial, UTE, Rumipamba y, Bourgeois, Quito 170147, Ecuador
Additional
Authors:
Diego Moreno, MD
Abstract:
Introduction: Chronic pruritus poses a therapeutic challenge, particularly when it remains refractory to traditional management. While often associated with cutaneous or systemic conditions, persistent exposure to aeroallergens such as dust mites may trigger predominantly skin-related symptoms, even in the absence of respiratory complaints. The nasal mucosa serves as a key entry point for these allergens, and saline nasal irrigation may modulate the Th2-mediated immune response by reducing histamine release and the production of pruritogenic cytokines. Objectives: To present a case of severe urticaria and pruritus unresponsive to standard therapies that resolved completely with the introduction of nasal saline irrigations, and to propose a pathophysiological mechanism supporting its role as a therapeutic strategy in allergic conditions with cutaneous manifestations. Results: A 24-year-old, previously healthy man, presented with intensely pruritic, erythematous papules and wheals after two years of daily exposure to ocean water. Symptoms persisted despite multiple courses of first- and second-generation antihistamines, as well as topical and systemic corticosteroids. Allergy testing was positive for dust mites and cockroaches. He was started on a regimen of second-generation antihistamines, an emollient cream (applied three times daily), and twice-daily nasal saline irrigations. Within 24 hours of initiating nasal washes, all cutaneous symptoms resolved completely. Notably, symptoms would reliably recur when nasal irrigations were discontinued for more than one day. At six-month follow-up, he remains asymptomatic under this treatment plan. Conclusion: Nasal irrigation may play a key role in controlling allergic pruritus, even in patients without respiratory symptoms. This case highlights how simple, non-invasive, and low-cost interventions can be remarkably effective, and supports their consideration as part of the therapeutic approach to chronic pruritus.
