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Patients with prurigo nodularis (PN) present with pruritus which may lead to sleep disturbances and systemic comorbidities. The objective of our study was to determine the risk of sleep disorders in PN and its association with systemic inflammation and adverse cardiovascular outcomes. We conducted a retrospective population-level cohort using a global health records database to analyze the development of sleep disorders, C-reactive protein (CRP) levels, and risk of cardiovascular disease and mortality in PN compared to controls. PN patients had increased risk of general sleep disorders (RR 1.47, 95%CI 1.42-1.52, obstructive sleep apnea (1.61, 1.54-1.69), insomnia (1.37, 1.29-1.45), hypersomnia (1.47, 1.32-1.64), and restless legs syndrome (1.45, 1.28-1.65). Additionally, PN with sleep disorders had higher CRP levels than PN without sleep disorders (16.2 mg/L vs. 10.6 mg/L). PN patients with sleep disorders were more likely to develop cardiovascular comorbidities, including type 2 diabetes mellitus (RR 2.45, 95%CI 2.25-2.66), metabolic syndrome (4.16, 3.31-5.22), myocardial infarction (2.87, 2.52-3.22), venous thromboembolism (2.93, 2.55-3.39), and greater mortality (HR 1.47, 95%CI 1.34-1.62) compared to PN patients without sleep disorders. Our findings suggest that PN patients are at greater risk of developing various sleep disorders that are associated with adverse cardiovascular outcomes., Competing Interests: Declarations. IRB status: Waived. Patient consent: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Pain and itch are regulated by a diverse array of neuropeptides and their receptors in superficial laminae of the spinal cord dorsal horn (DH). Neuropeptide Y (NPY) is normally expressed on DH neurons but not sensory neurons. By contrast, the Npy2r receptor (Y2) is expressed on the central and peripheral terminals of sensory neurons but not on DH neurons. Neurophysiological slice recordings indicate that Y2-selective agonists inhibits spinal neurotransmitter release from sensory neurons. However, behavioral pharmacology studies indicate that Y2 agonists exert minimal changes in nociception, even after injury. Additional discrepancies in the behavioral actions of the Y2-antagonist BIIE0246 - reports of either pronociception or antinociception - have now been resolved. In the normal state, spinally-directed (intrathecal) administration of BIIE0246 elicits ongoing nociception, hypersensitivity to sensory stimulation, and aversion. Conversely, in the setting of nerve injury and inflammation, intrathecal BIIE024 reduced not only mechanical and thermal hypersensitivity, but also a measure of the affective dimension of pain (conditioned place preference). When administered in chronic pain models of latent sensitization, BIIE0246 produced a profound reinstatement of pain-like behaviors. We propose that tissue or nerve injury induces a G protein switch in the action of NPY-Y2 signaling from antinociception in the naïve state to the inhibition of mechanical and heat hyperalgesia in the injured state, and then a switch back to antinociception to keep LS in a state of remission. This model clarifies the pharmacotherapeutic potential of Y2 research, pointing to the development of a new non-opioid pharmacotherapy for chronic pain using Y2 antagonists in patients who do not develop LS., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Background: As the available treatments for moderate-to-severe atopic dermatitis (AD) expand, understanding patient and physician preferences becomes crucial for informed decision-making., Objective: To quantify patient and physician preferences for biologics and oral systemic AD treatment attributes., Materials and methods: We conducted a cross-sectional, online discrete choice experiment (DCE) involving 306 AD patients and 206 physicians throughout the United Kingdom and Germany. Qualitative interviews identified the key attributes for inclusion in the DCE. Each choice task comprised two hypothetical patient profiles. Data were analyzed using a random-parameters logit model., Results: Results indicated a significant emphasis on efficacy, with reducing sleep disturbance and itch ranking first and second among patients, and the reverse for physicians. Time to itch relief was the third most important efficacy attribute for both groups, but relatively more important for patients than for physicians. For both groups, the risk of eye problems was the most important safety concern of those included. Mode of administration was not of great importance compared to efficacy and safety attributes., Conclusions: Our findings suggest patients prioritize sleep disturbance, an attribute not captured in prior preference studies in AD, time to itch relief and itch. These findings emphasize the importance of addressing sleep-related issues, whilst also targeting fast itch control, to enhance patients' well-being.

Murine models are vital preclinical and biological tools for studying itch. In this paper, we explore how these models have enhanced our understanding of the mechanisms underlying itch through both acute and chronic itch models. We provide detailed protocols and recommend experimental setups for specific models to guide researchers in conducting itch research. We distinguish between what constitutes a bona fide pruritogen versus a stimulus that causes pruritogen release, an acute itch model versus a chronic itch model, and how murine models can capture aspects of pruritus in human disease. Finally, we highlight how mouse models of itch have transformed our understanding and development of therapeutics for chronic pruritus in patients., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Conflicts of interest Dr Kwatra is an advisory board member/consultant for AbbVie, Amgen, Arcutis Biotherapeutics, ASLAN Pharmaceuticals, Cara Therapeutics, Castle Biosciences, Celldex Therapeutics, Galderma, Genzada Pharmaceuticals, Incyte Corporation, Johnson & Johnson, LEO Pharma, Novartis Pharmaceuticals Corporation, Pfizer, Regeneron Pharmaceuticals, and Sanofi and has served as an investigator for Galderma, Incyte, Pfizer, and Sanofi. Authors Ma, Bao, Ahmadi, and Zhang have no conflicts of interest to declare.

Background: Lebrikizumab improved itch, interference of itch on sleep, and quality of life (QoL) in patients with moderate-to-severe atopic dermatitis (AD), in two Phase 3 trials at 16 weeks compared to placebo., Objectives: We assess improvements in itch and sleep interference due to itch and their impact on QoL measurements after treatment., Methods: Data were analyzed from ADvocate1 (NCT04146363) and ADvocate2 (NCT04178967) in patients with moderate-to-severe AD. QoL was evaluated using Dermatology Life Quality Index (DLQI) at Week 16 in patients (>16 years of age) who were itch responders/non-responders (defined as ≥4-point improvement in Pruritus Numeric Rating Scale) or Sleep-Loss Scale responders/non-responders (defined as ≥2-point improvement in itch interference on sleep)., Results: In ADvocate1 and ADvocate2, significantly greater proportions of itch responders had a clinically meaningful improvement in measures related to QoL (DLQI scores (0/1), ≤5 DLQI total score and ≥4-point DLQI improvement) compared to itch non-responders. In both studies, a significantly greater proportion of Sleep-Loss Scale responders, reported a DLQI score of (0/1), DLQI total score of ≤5 and DLQI improvement of ≥4 points compared to Sleep-Loss Scale non-responders., Conclusions: Improvement in itch and sleep interference due to itch is associated with improvement in the QoL of patients after treatment with lebrikizumab for moderate-to-severe AD., ClinicalTrials.gov registration NCT04146363 (ADvocate1) and NCT04178967 (ADvocate2).

Purpose: Prurigo nodularis (PN) is a skin disease characterized by intensely itchy skin nodules and is associated with a significant healthcare resource utilization (HCRU). This study aimed to estimate the HCRU of patients in England with PN overall and moderate-to-severe PN (MSPN) in particular., Methods: This retrospective cohort study used data from the Clinical Practice Research Datalink and Hospital Episode Statistics in England. Patients with Mild PN (MiPN) were matched to patients with MSPN by age and gender for the primary analysis. Patients were enrolled in the study between 1st April 2007 and 1st March 2019. All-cause HCRU was calculated, including primary and secondary care contacts and costs (cost-year 2022)., Results: Of 23,522 identified patients, 8,933 met the inclusion criteria, with a primary matched cohort of 2,479 PN patients. During follow up, the matched cohort's primary care visits were 21.27 per patient year (PPY) for MSPN group and 11.35 PPY for MiPN group. Any outpatient visits were 10.72 PPY and 4.87 PPY in MSPN and MiPN groups, respectively. Outpatient dermatology visits were 1.96 PPY and 1.14 PPY in MSPN and MiPN groups, respectively., Conclusion: PN, especially MSPN, has a high HCRU burden in England, highlighting the need for new and improved disease management treatments.

Purpose: Based on a potential shared pathophysiology tied to mast cell activity and neurogenic inflammation that may link pruritus and chronic cough (CC), this study, leveraging the All of Us database, examines the association between the two conditions., Materials and Methods: A nested case-control comparison was used to examine the association, identifying cases with SNOMED codes 418363000 (pruritus) and 68154008 (CC). Matching was performed on a 1:4 ratio by age, sex, and ethnicity using the MatchIt package in R, followed by maximum likelihood method to estimate odds ratios (ORs) and 95% confidence intervals from 2x2 contingency tables., Results: CC patients ( n  = 2,388) were more than twice as likely to be diagnosed with pruritus (OR: 2.65) and pruritus patients ( n  = 22,496) were more than twice as likely to be diagnosed with CC (OR: 2.57), than respective matched controls., Conclusions: These results highlight the potential bidirectional relationship between CC and pruritus, suggesting possible shared immune and neural pathways. Treatments like difelikefalin and nalbuphine that modulate these pathways, alongside P2X3 targeting agents, are emerging as potential therapeutic approaches for itch and chronic cough given the possible interconnected pathophysiology. This study's insights into the associations between pruritus and CC may pave the way for targeted therapeutic strategies that address their shared mechanisms.

Purpose: The presence of wheals or hives has been viewed as a hallmark symptom of urticaria, a highly debilitating disease. This study explores our experience with omalizumab in patients with apparent mast-cell mediated pruritus in the absence of hives., Materials and Methods: This is a retrospective case series examining all patients with mast cell-mediated pruritus in the absence of hives from April 2022 to May 2024 at a tertiary referral clinic at Icahn School of Medicine at Mount Sinai in New York. Peak pruritus-numerical rating scale (PP-NRS) itch score changes over time were recorded and analyzed., Results: Six patients (67% women; mean [SD] age, 47.67 [13.52] years) were included in the analysis. The median [IQR] pruritus PP-NRS itch score before omalizumab injection was 9 [6 - 10] and the final median [IQR] PP-NRS itch score was 2.5 [0 - 5]. The mean [SD] reduction in the PP-NRS itch score was 6 [3.16]., Conclusions: This study suggests that patients with evidence of mast cell-mediated pruritus can be identified based on clinical features and may benefit from omalizumab therapy.

Background: Though Janus kinase inhibitors such as upadacitinib rapidly relieve itch in atopic dermatitis (AD) patients, how early itch relief impacts later skin clearance is not examined., Objectives: This study aims to determine if early itch relief by upadacitinib could predict complete skin clearance in later phases., Methods: This retrospective study involved 105 patients with moderate-to-severe AD treated with upadacitinib 15 mg/day. Eczema area and severity index (EASI), atopic dermatitis control tool, and achievement rate of EASI 100 were evaluated at weeks 4, 12, and 24. The threshold of early peak pruritus-numerical rating scale (PP-NRS) predicting later skin clearance was assessed by area under the receiver-operating characteristic curve, and predictors for EASI 100 achievement were determined by logistic regression analysis., Results: The rate of achieving EASI 100 at week 24 was extremely higher in patients who achieved week 2 PP-NRS ≤ 1 (42.9%) than in non-achievers (1.4%). The logistic regression analysis showed that the achievement of week 2 PP-NRS ≤ 1 and low body mass index were associated with achievement of EASI 100 at weeks 12 and 24., Conclusions: The achievement of week 2 PP-NRS ≤ 1 may predict later skin clearance in upadacitinib treatment.

Even though pruritus affects a significant number of people with chronic disease, it is rarely adequately treated. Drug therapies often rely on antihistamines, which have not shown to be beneficial in systemic pruritus. Hydroxyzine is frequently used to treat pruritus associated with kidney failure. Since Canada's sole manufacturer of hydroxyzine is no longer making this product, this is an ideal time to review the mechanisms of itch in advanced organ failure and the specific therapies that give relief. Although there is literature describing itch in patients with cancer, this article is limited to pathogenesis and treatment of systemic itch secondary to chronic, noncancer diseases. We summarize recent systematic reviews, although the studies included in these reviews are often small, and mostly cohort studies.

Background and Purpose: While pain and itch are both commonly associated with chronic dermatitis (CD), the molecular mechanisms underlying these debilitating symptoms is not well understood. This study aims to identify novel, endogenous compounds that mediate CD-associated pain and itch., Experimental Approach: Lesional skin of CD model mice was examined using unbiased metabolomic analysis to identify candidate pain or itch inducing compounds in CD. Sphingosine-1-phosphate (S1P) concentration in CD model skin was analysed using UPLC/MS/MS. Behaviour, calcium imaging and immunofluorescence staining were used to determine the pain and itch effects and mechanisms of the identified CD-related compounds., Key Results: In the lesional skin of CD model mice, 136 compounds were significantly changed. These compounds are predominately associated with the sphingolipids metabolism pathway. S1P is significantly increased in the lesional skin . The TRPV4 channel was critical for S1P induced itch and pain. Sphingosine kinase 2 (SPHK2), the key enzyme controlling S1P synthesis, was significantly increased in lesional skin. ABC294640, a SPHK2 inhibitor, significantly decreased S1P concentration in lesional CD model skin, as well as in model associated epidermal hyperplasia and chronic pain and itch. In CD patients, SPHK2 expression and S1P concentration were significantly elevated compared to healthy control skin., Conclusion and Implications: Our results indicate that, in CD, increased S1P induces chronic pain and itch partly through TRPV4. Inhibition of S1P synthesis or the S1P/S1P receptor-TRPV4 pathway are promising treatment strategies for CD-associated pain and itch., (© 2024 British Pharmacological Society.)

Atopic dermatitis (AD) is a chronic inflammatory skin disease with multifactorial and unclear pathogenesis. Its development is characterized by two key elements: epigenetic dysregulation of molecular pathways involved in AD pathogenesis and disrupted skin and gut microbiota (dysbiosis) that jointly trigger and maintain chronic inflammation, a core AD characteristic. Current data suggest that failed inflammation resolution is the main pathogenic mechanism underlying AD development. Inflammation resolution is provided by specialized pro-resolving mediators (SPMs) derived from dietary polyunsaturated fatty acids acting through cognate receptors. SPM levels are reduced in AD patients. Administration of SPMs or their stable, small-molecule mimetics and receptor agonists, as well as supplementation with probiotics/prebiotics, demonstrate beneficial effects in AD animal models. Epidrugs, compounds capable of restoring disrupted epigenetic mechanisms associated with the disease, improve impaired skin barrier function in AD models. Based on these findings, we propose a novel, multilevel AD treatment strategy aimed at resolving chronic inflammation by application of SPM mimetics and receptor agonists, probiotics/prebiotics, and epi-drugs. This approach can be used in conjunction with current AD therapy, resulting in AD alleviation.

Itch is one of the most prevalent symptoms experienced by patients with inflammatory skin conditions, yet it is also one of the most debilitating. Patients suffering from chronic itch have been found to have significantly higher stress levels compared with those not experiencing itch. In fact, recent studies have revealed a bidirectional relationship between stress and itch, where each condition worsens the other. This is thought to be driven by the vicious itch-scratch cycle, which is fueled by underlying inflammation. The precise molecular pathways and mediators involved, however, remain unclear. This narrative review discusses the existing research on the relationship between stress and itch and outlines future research directions that will be necessary to advance our understanding and treatment of these conditions. Given that the effective management of both symptoms often requires a combined treatment approach, further investigation into their shared mechanisms is essential for identifying successful therapies and improving patient outcomes.

Treating psoriasis presents a major clinical challenge because of the limitations associated with traditional topical glucocorticoid therapy. This study introduced a drug delivery system utilizing zinc-doped mesoporous silica nanoparticle (Zn-MSN) and microneedle (MN), designed to enhance drug utilization for prolonged anti-inflammatory and anti-itch effects. The MN system facilitated the transdermal delivery of betamethasone dipropionate (BD), allowing its slow release. The BD@Zn-MSN-MN system promoted the polarization of macrophages towards the anti-inflammatory M2 phenotype, achieving superior anti-inflammatory effects compared to the clinically used BD cream. Additionally, this study demonstrated that BD@Zn-MSN-MN could further alleviate itching in psoriasis-afflicted mice by decreasing the excitability of the transient receptor potential vanilloid V1 (TRPV1) ion channel positive neurons and reducing the release of calcitonin gene-related peptide (CGRP) in the dorsal root ganglion (DRG). These findings offer new insights and effective therapeutic options for the future design of transdermal drug delivery for psoriasis., Competing Interests: Declarations Ethics approval and consent to participate The animal experiments were approved by the Ethics Committee for Experimental Use of Animals of the Shanghai Jiao Tong University School of Medicine (approval code: #SYXK-2013-0050). Consent for publication All authors agree for publication. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Melanosomes play a pivotal role in skin color and photoprotection. In contrast to the well-elucidated pathway of melanosome biogenesis, the process of melanosome degradation, referred to as melanophagy, is largely unexplored. Previously, we discovered that 3,4,5-trimethoxycinnamate thymol ester (TCTE) effectively inhibits skin pigmentation by activating melanophagy. In this study, we discovered a new regulatory signaling cascade that controls melanophagy in TCTE-treated melanocytes. ITCH (itchy E3 ubiquitin protein ligase) facilitates ubiquitination of the melanosome membrane protein MLANA (melan-A) during TCTE-induced melanophagy. This ubiquitinated MLANA is then recognized by an autophagy receptor protein, OPTN (optineurin). Additionally, a phospho-kinase antibody array revealed that TCTE activates PTK2 (protein tyrosine kinase 2), which phosphorylates ITCH, enhancing the ubiquitination of MLANA. Furthermore, inhibition of either PTK2 or ITCH disrupts the ubiquitination of MLANA and the MLANA-OPTN interaction in TCTE-treated cells. Taken together, our findings highlight the critical role of the PTK2-ITCH-MLANA-OPTN cascade in orchestrating melanophagy progression. Abbreviations : α-MSH: alpha-melanocyte-stimulating hormone; dichlone: 2,3-dichloro-1,4-naphthoquinone; ITCH: itchy E3 ubiquitin protein ligase; MITF: melanocyte inducing transcription factor; MLANA: melan-A; NBR1: NBR1 autophagy cargo receptor; OPTN: optineurin; PINK1: PTEN induced kinase 1; PTK2: protein tyrosine kinase 2; SQSTM1/p62: sequestosome 1; TCTE: 3,4,5-trimethoxycinnamate thymol ester; TPC2: two pore segment channel 2; VDAC1: voltage dependent anion channel 1.

Introduction: Hidradenitis suppurativa (HS) can severely affect the quality of life (QoL) and is linked to psychological distress, including anxiety, depression, and reduced self-esteem. Stigmatization due to physical appearance may significantly contribute to the psychological burden and impact on QoL for HS patients. This study investigates the association between stigmatization, depression, anxiety, and health- and disease-related variables among HS patients in Europe., Patients and Methods: This observational cross-sectional multicenter study was conducted across 22 dermatological outpatient clinics in 17 European countries. Data collected included sociodemographic variables, general health variables, disease-related variables, perceived stigmatization (PSQ), and mental health (PHQ-2, GAD-2)., Results: Of the 5487 dermatological patients, 142 (2.6%) were diagnosed with HS, and data from 135 patients (70.1% women, mean age 38.2 years) who completed the PSQ questionnaire were analyzed. Scores on the stigmatization measure indicated that significant stigmatization levels were present in the sample. Linear regression models revealed a significant relationship between stigmatization and both the duration of HS and the presence of itch. Similar findings were noted for the PSQ "confused/staring behavior" scale with depression. The PSQ "absence of friendly behavior" scale was inversely associated with general health status, whereas the "hostile behavior" scale was positively linked to depression., Conclusion: HS patients experience significant stigmatization linked to disease duration, itch, and depression. Comprehensive management, including screening for psychosocial co-morbidity, is essential, as is providing access to psychological interventions that support patients to both manage internal distress and the potential reactions of others., (© 2024 the International Society of Dermatology.)

Caring for patients with hard-to-heal (chronic) wounds requires a multifaceted approach that addresses their diverse needs, which can contribute to the complexity of care. Wound care providers must have a comprehensive understanding of the patient's comorbid conditions and psychosocial issues to provide personalised and effective treatment. Key quality indicators for effective wound care involves not only selecting appropriate local wound care products, such as foam dressings, but also addressing individual patient experiences of wound-related pain, odour, itch, excessive wound drainage, and self-care needs. The purpose of this review is to inculcate the wound care practice community, research scientists and healthcare industry with a sense of accountability in order to work collaboratively in addressing these unmet care needs.

Despite remarkable progress in understanding the fundamental bases of itching, its cortical mechanisms remain poorly understood. Herein, the causal contributions of defined anterior cingulate cortex (ACC) neuronal populations to acute itch modulation in mice are established. Using cell type-specific manipulations, the opposing functions of ACC glutamatergic and GABAergic neurons in regulating acute itching are demonstrated. Photometry studies indicated that ACC glutamatergic neurons are activated during scratching induced by both histamine and chloroquine, whereas the activation pattern of GABAergic neurons is complicated by GABAergic subpopulations and acute itch modalities. By combining cell type- and projection-specific techniques, a thalamocortical circuit is further identified from the mediodorsal thalamus driving the itch-scratching cycle related to histaminergic and non-histaminergic itching, which is contingent on the activation of postsynaptic parvalbumin-expressing neurons in the ACC. These findings reveal a cellular and circuit signature of ACC neurons orchestrating behavioral responses to itching and may provide insights into therapies for itch-related diseases., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Competing Interests: Conflicts of interest None disclosed.

Anoctamin 1 (ANO1/TMEM16A) encodes a Ca 2+ -activated Cl - channel. Among ANO1's many physiological functions, it plays a significant role in mediating nociception and itch. ANO1 is activated by intracellular Ca 2+ and depolarization. Additionally, ANO1 is activated by heat above 44 °C, suggesting heat as another activation stimulus. ANO1 is highly expressed in nociceptors, indicating a role in nociception. Conditional Ano1 ablation in dorsal root ganglion (DRG) neurons results in a reduction in acute thermal pain, as well as thermal and mechanical allodynia or hyperalgesia evoked by inflammation or nerve injury. Pharmacological interventions also lead to a reduction in nocifensive behaviors. ANO1 is functionally linked to the bradykinin receptor and TRPV1. Bradykinin stimulates ANO1 via IP3-mediated Ca 2+ release from intracellular stores, whereas TRPV1 stimulates ANO1 via a combination of Ca 2+ influx and release. Nerve injury causes upregulation of ANO1 expression in DRG neurons, which is blocked by ANO1 antagonists. Due to its role in nociception, strong and specific ANO1 antagonists have been developed. ANO1 is also expressed in pruritoceptors, mediating Mas-related G protein-coupled receptors (Mrgprs)-dependent itch. The activation of ANO1 leads to chloride efflux and depolarization due to high intracellular chloride concentrations, causing pain and itch. Thus, ANO1 could be a potential target for the development of new drugs treating pain and itch., Competing Interests: Declaration of competing interest None, (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Itch is an uncomfortable feeling that evokes a desire to scratch. This protective reflex can effectively eliminate parasites that invade the skin. When itchy skin becomes severe or lasts for more than six weeks, it has deleterious effects on both quality of life and productivity. Despite decades of research, the complete molecular and cellular coding of chronic itch remains elusive. This persistent condition often defies treatment, including with antihistamines, and poses a significant societal challenge. Obtaining pathophysiological insights into the generation of chronic itch is essential for understanding its mechanisms and the development of innovative anti-itch medications. In this review we provide a systematic overview of the recent advancement in itch research, alongside the progress made in drug discovery within this field. We have examined the diversity and complexity of the classification and mechanisms underlying the complex sensation of itch. We have also delved into recent advancements in the field of itch mechanism research and how these findings hold potential for the development of new itch treatment medications. But the treatment of clinical itch symptoms still faces significant challenges. Future research needs to continue to delve deeper, not only to discover more itch-related pathways but also to explore how to improve treatment efficacy through multitarget or combination therapy., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Background & Methods: Through the identification of 22 803 cases of chronic pruritus, with a control group comprising 91 212 participants from a national database, we performed a comparative analysis revealing that patients with chronic pruritus had a significantly higher prevalence of liver disease compared to controls., Results: Upon reverse analysis, we similarly found patients with liver disease had a significantly higher prevalence of chronic pruritus. Subsequent multivariate logistic regression highlighted increased odds for several liver diseases in the pruritus cohort, including metabolic dysfunction-associated steatotic liver disease (aOR 1.65, 95% CI 1.53-1.78) and alcohol-related liver disease (aOR 1.69, 95% CI 1.43-1.98). The increased odds were most pronounced for hepatitis B (aOR 2.01, 95% CI 1.67-2.42) and cholangitis + primary sclerosing cholangitis + primary biliary cholangitis (aOR 1.81, 95% CI 1.65-1.99)., Conclusion: Our results reveal a strong correlation between pruritus in hepatic pathologies different than commonly reported cholestatic diseases., (© 2024 The Author(s). Liver International published by John Wiley & Sons Ltd.)

Introduction: Allergic contact dermatitis (ACD), a prevalent skin disorder affecting up to 20% of the population, triggers significant discomfort and health implications. Our research investigates the pivotal role of Vascular Endothelial Growth Factor A (VEGFA) in chronic itching associated with ACD., Methods: Bioinformatics methods were utilized to identify differentially expressed genes (DEGs) between ACD models and patients. In vivo models of chronic pruritus in mice induced by 2,4-dinitrofluorobenzene (DNFB) were employed. Mice were administered subcutaneously with a VEGFA inhibitor, sFlt1, and compared to a control group. Real-time RT-PCR, Western blot, and immunohistochemical staining were performed to evaluate VEGFA expression and the impact of sFlt1 on itching behavior., Results: The analysis revealed that VEGFA is significantly upregulated in ACD skin, primarily expressed by keratinocytes. Administration of the VEGFA inhibitor sFlt1 in the ACD mouse model led to a substantial reduction in scratching behavior, indicating that VEGFA may mediate pruritus through the VEGFA-VEGFR2-PI3K-TRPV1 signaling pathway., Discussion: These findings suggest that VEGFA plays a crucial role in ACD-associated pruritus and may serve as a potential therapeutic target. However, further research is required to validate these findings and to explore additional molecular pathways involved in the pruritic response in ACD., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Liu et al.)

Background: Atopic dermatitis (AD) is one of the most prevalent skin diseases, but there are numerous knowledge gaps surrounding the impact this disease has on quality of life (QoL), mental health, and out-of-pocket expenses involved in the management of AD. The available scientific evidence on the multidimensional burden of AD is usually based on studies with measures reported by patients themselves., Methods: In this context, the MEASURE-AD trial was developed as a cross-sectional, multicenter, multinational trial using patient- and physician-reported measures to characterize the multidimensional burden of AD in adults with moderate-to-severe AD., Results: This paper presents the results of the Spanish cohort. We found that Spanish adults with moderate-to-severe AD and high EASI score (21.1-72) had a significantly increased disease burden, high severity of symptoms such as itch and sleep disturbances, impaired mental health and QoL, higher use of health care resources, and more out-of-pocket expenses than patients with low EASI scores (0-7 or 7.1-21)., Conclusions: This study provides information to better understand disease burden, and identify aspects to be improved in the management of AD., (Copyright © 2024 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.)

Epithelial barriers such as the skin, lung, and gut, in addition to having unique physiologic functions, are designed to preserve tissue homeostasis upon challenge with a variety of allergens, irritants, or pathogens. Both the innate and adaptive immune systems play a critical role in responding to epithelial cues triggered by environmental stimuli. However, the mechanisms by which organs sense and coordinate complex epithelial, stromal, and immune responses have remained a mystery. Our increasing understanding of the anatomic and functional characteristics of the sensory nervous system is greatly advancing a new field of peripheral neuroimmunology and subsequently changing our understanding of mucosal immunology. Herein, we detail how sensory biology is informing mucosal neuroimmunology, even beyond neuroimmune interactions seen within the central and autonomic nervous systems., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Atopic dermatitis (AD) is a chronic inflammatory skin condition that can be difficult to treat due to a complex etiology and diverse clinical presentations. Itch is the most common symptom associated with AD with profound negative impact on quality of life. Thus, the adjunctive management of itch in patients with AD is needed to control and reduce disease burden. Supplemental treatment options are continuously emerging and undergoing testing in clinical trials. This article summarizes the latest data on topical and systemic adjunctive therapies for AD safety and efficacy in reducing itch., Competing Interests: Disclosure Dr G. Yosipovitch has received funding or grants from Sanofi, France, Regeneron Pharmaceuticals, United States, Pfizer, United States, Escient Health, Novartis, Switzerland, Eli Lilly, Celldex, United States, and Kiniksa Pharmaceuticals, United States. He has participated on a Data Safety Monitoring/Advisory board and received consulting support from Abbive, Arcutis, Escient Health, Eli Lilly, Galderma, LEO Pharma, Novartis, Pfizer, Pierre Fabre, Regeneron Pharmaceuticals Inc., Sanofi, Trevi Therapeutics, Vifor, Kamari, Kiniksa, and GSK. Patents include Topical Acetaminophen Formulations for Itch Relief., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Itch terminology is ambiguous. How itch was described in online materials and how terminology influenced the readability of these materials was previously unknown., Materials and Methods: Two groups of search terms, itch and prurigo, were translated into five of the most prevalent European Union (EU) languages. The itch group consisted of "itch" and "pruritus." The prurigo group consisted of "prurigo," "prurigo nodularis," and "chronic prurigo". Then, a search of the terms in each language was queried in the Google search engine in the private mode of the Internet browser. The first 50 results generated were assessed for suitability. Patient education was the primary objective of the materials provided, with no barriers or advertisements included. In cases where the terms yielded identical outcomes, any duplicated materials were omitted from the analysis. When translating search terms within a group led to just one shared transcription, the results were attributed to the search term with the most similar syntax. The Lix score was utilized to assess readability., Results: 314 articles in English, German, Italian, French, and Spanish were evaluated. The term "pruritus" was the most commonly used description for the sensation of itching, with 142 (45%) articles included. Overall, the mean Lix score was 54 ± 9, classifying all articles as hard to comprehend. Articles in the itch group had significantly (P < 0.001) lower mean Lix score (52 ± 9) than materials in the prurigo group (56 ± 10)., Conclusions: Despite being more accessible to conceptualize, skin conditions such as prurigo had lower readability compared to information about the itch itself. The distinction between "itch" and "pruritus" was unclear., (© 2024 the International Society of Dermatology.)

Chronic pruritus 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. Phototherapy, laser, 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. In this narrative review, we provided an overview of these physical modalities and their role in itch management., Competing Interests: Conflicts of interest None disclosed., (Copyright © 2024 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Diospyros lotus has been traditionally used in Asia for medicinal purposes, exhibiting a broad spectrum of pharmacological effects including antioxidant, neuroprotective and anti‑inflammatory properties. While the anti‑itch effect of D. lotus leaves has been reported, studies on the detailed mechanism of action in microglia and astrocytes, which are members of the central nervous system, have yet to be revealed. The present study aimed to investigate effects of D. lotus leaf extract (DLE) and its main component myricitrin (MC) on itch‑related cytokines and signaling pathways in lipopolysaccharide (LPS)‑stimulated microglia. The effect of DLE and MC on activation of astrocyte stimulated by microglia was also examined. Cytokine production was evaluated through reverse transcription PCR and western blot analysis. Signaling pathway was analyzed by performing western blotting and immunofluorescence staining. The effect of microglia on astrocytes activation was evaluated via western blotting for receptors, signaling molecules and itch mediators and confirmed through gene silencing using short interfering RNA. DLE and MC suppressed the production of itch‑related cytokine IL‑6 and IL‑31 in LPS‑stimulated microglia. These inhibitory effects were mediated through the blockade of NF‑κB, MAPK and JAK/STAT pathways. In astrocytes, stimulation by microglia promoted the expression of itch‑related molecules such as oncostatin M receptor, interleukin 31 receptor a, inositol 1,4,5‑trisphosphate receptor 1, lipocalin‑2 (LCN2), STAT3 and glial fibrillary acidic protein. However, DLE and MC significantly inhibited these receptors. Additionally, astrocytes stimulated by microglia with IL‑6, IL‑31, or both genes silenced did not show activation of LCN2 or STAT3. The findings of the present study demonstrated that DLE and MC could suppress pruritic activity in astrocytes induced by microglia‑derived IL‑6 and IL‑31. This suggested the potential of DLE and MC as functional materials capable of alleviating pruritus.

Background: Moderate-to-severe atopic dermatitis (AD) greatly impacts children/caregivers., Objective: Evaluate the impact of treatment with dupilumab on caregiver- and patient-reported AD symptoms and quality of life (QoL) in young children., Methods: In the LIBERTY AD PRESCHOOL (randomized, placebo-controlled) study, children aged 6 months to 5 years with moderate-to-severe AD received dupilumab or placebo plus low-potency topical corticosteroids for 16 weeks. This posthoc analysis assessed the change from baseline to week 16 in caregiver-reported outcome measures of AD symptoms (eg, itch and sleep) and QoL of patients and their caregivers/families., Results: Dupilumab (n = 83) vs placebo (n = 79) provided significant improvements in caregiver-reported AD symptoms and QoL. Significant improvements were seen as early as week 4 and sustained through the end of the study. Additionally, dupilumab vs placebo provided rapid and significant improvement in QoL measures for the patients' caregivers/families., Limitations: Few patients aged <2 years; significance only reported for prespecified endpoints; Infant's Dermatitis QoL Index severity strata adopted from Children's Dermatology Life Quality Index., Conclusion: Dupilumab improved AD symptoms and QoL in patients and their caregivers/families., Competing Interests: Conflicts of interest Dr Paller is a consultant for and has received honoraria from Aegerion Pharma, Azitra, BioCryst, Boehringer Ingelheim, Bristol Myers Squibb, Castle Creek Biosciences, Eli Lilly, Janssen, Krystal Biotech, LEO Pharma, Novartis, Regeneron Pharmaceuticals Inc, Sanofi, Seanergy, TWI Biotechnology, and UCB, is an investigator for AbbVie, Dermavant, Eli Lilly, Incyte, Janssen, Krystal Biotech, LEO Pharma, and UCB, and is on the data and safety monitoring boards of AbbVie, Abeona Therapeutics, Catawba Research, Galderma, and InMed Pharmaceuticals. Dr Silverberg has received honoraria as a consultant and/or advisory board member from AbbVie, Alamar Biosciences, Aldena Therapeutics, Amgen, AOBiome, Arcutis Biotherapeutics, Arena Pharmaceuticals, Asana BioSciences, Aslan Pharmaceuticals, BiomX, Biosion, Bodewell, Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Castle Biosciences, Celgene, Connect Biopharma, CorEvitas, Dermavant, Dermira, DermTech, Eli Lilly, Galderma, GSK, Incyte, Kiniksa Pharmaceuticals, LEO Pharma, Menlo Therapeutics, Novartis, Optum, Pfizer, RAPT Therapeutics, Recludix Pharma, Regeneron Pharmaceuticals Inc, Sanofi, Shaperon, Target-RWE, UNION therapeutics, and UpToDate, has received speaker fees from AbbVie, Eli Lilly, LEO Pharma, Pfizer, Regeneron Pharmaceuticals Inc, and Sanofi, and institution grants from Galderma, Incyte, and Pfizer. Dr Simpson has received personal fees from AbbVie, Advances in Cosmetic and Medical Dermatology Hawaii, Amgen, AOBiome, Arcutis Biotherapeutics, Arena Pharmaceuticals, Aslan Pharmaceuticals, Boehringer Ingelheim, BMS, Boston Consulting Group, Collective Acumen, CorEvitas, Dermira, Eli Lilly, Evelo Biosciences, Evidera, Excerpta Medica, Forté Biosciences, Fraunhofer, Galderma, GSK, Incyte, Janssen, Johnson & Johnson, Kyowa Kirin, LEO Pharma, Medscape, Merck, Maui Derm, MJH Life Sciences, MLG Operating, Pfizer, Physicians World, PRImE, Regeneron Pharmaceuticals Inc, Revolutionizing Atopic Dermatitis, Roivant Sciences, Sanofi, Trevi Therapeutics, Valeant, Vindico Medical Education, and WebMD, and has received grants as a principal investigator from AbbVie, Amgen, Arcutis Biotherapeutics, Aslan Pharmaceuticals, Castle Creek Biosciences, CorEvitas, Dermavant, Dermira, Eli Lilly, Incyte, Kymab, Kyowa Kirin, National Jewish Health, LEO Pharma, Pfizer, Regeneron Pharmaceuticals Inc, Sanofi, and Target RWE. Dr Cork is an investigator and/or consultant for AbbVie, Astellas Pharma, Boots, Dermavant, Galapagos, Galderma, Hyphens Pharma, Johnson & Johnson, LEO Pharma, L’Oréal, Menlo Therapeutics, Novartis, Oxagen, Pfizer, Procter & Gamble, Reckitt Benckiser, Regeneron Pharmaceuticals Inc, and Sanofi. Dr Arkwright is an investigator at Regeneron Pharmaceuticals Inc and LEO Pharma, and is a research grant advisor and lecturer with Sanofi. Dr Chen, Dr Bansal, and Dr Wang are employees/ shareholders of Regeneron Pharmaceuticals Inc. Dr Prescilla and Dr Marco are employees of Sanofi and may hold stock and/or stock options in the company. Dr Cork has no conflict of interest to declare., (Copyright © 2024 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Cough and itch are protective mechanisms in the body. Cough occurs as a reflex motor response to foreign body inhalation, while itch is a sensation that similarly evokes a scratch response to remove irritants from the skin. Both cough and itch can last for sustained periods, leading to debilitating chronic disorders that negatively impact quality of life. Understanding the parallels and differences between chronic cough and chronic itch may be paramount to developing novel therapeutic approaches. In this article, we identify connections in the mechanisms contributing to the complex cough and scratch reflexes and summarize potential shared therapeutic targets. An online search was performed using various search engines, including PubMed, Web of Science, Google Scholar, and ClinicalTrials.gov from 1983 to 2024. Articles were assessed for quality, and those relevant to the objective were analyzed and summarized. The literature demonstrated similarities in the triggers, peripheral and central nervous system processing, feedback mechanisms, immunologic mediators, and receptors involved in the cough and itch responses, with the neuronal sensitization processes exhibiting the greatest parallels between cough and itch. Given the substantial impact on quality of life, novel therapies targeting similar neuroimmune pathways may apply to both itch and cough and provide new avenues for enhancing their management., Competing Interests: Disclosure statement Disclosure of potential conflicts of interest: J. A. Smith has received funding or grants from Medical Research Council, Wellcome, National Institute for Health and Care Research Manchester Biomedical Research Centre and National Institute for Health and Care Research Manchester Clinical Research Facility, Merck Inc, and Bellus Health; and has received fees for consulting from Bayer Bellus Health, Nocion Therapeutics, Merck, Trevi Therapeutics, Shionogi, Bayer, Merck, Algernon, AstraZeneca, Boehringer Ingelheim, Cheisi, GSK, and Vitalograph. G Yosipovitch has received funding or grants from Sanofi, Regeneron Pharmaceuticals Inc, Pfizer, Escient Health, Novartis, Eli Lilly, Celldex, and Kiniksa Pharmaceuticals; has participated on a Data Safety Monitoring/Advisory Board for Bellus Health, Eli Lilly, Galderma, GSK, Kiniksa Pharamaceuticals, LEO Pharma, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Sanofi, and Trevi Therapeutics; received consulting support from AbbVie, Arcutis, Escient Health, Eli Lilly, Galderma, LEO Pharma, Novartis, Pfizer, Pierre Fabre, Regeneron Pharmaceuticals Inc, Sanofi, Trevi Therapeutics, Vifor, Kamari, Kiniksa, and GSK; and holds patents including Topical Acetaminophen Formulations for Itch Relief. The rest of the authors declare that they have no relevant conflicts of interest., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Studies have shown that disrupting the formation of the ligand-RET-GFRα complex could be an effective way of treating pain and itch. Compared to traditional high-throughput screens, DNA encoded libraries (DELs) have distinguished themselves as a powerful technology for hit identification in recent years. The present work demonstrates the use of DEL technology identifying compound 16 as the first GFRa2/GFRa3 small molecule inhibitor (0.1/0.2 μM respectively) selective over RET. This molecule represents an opportunity to advance the development of small-molecule inhibitors targeting the GFRα-RET interface for the treatment of pain and itch., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The experience of itch and its associated chronic conditions (i.e., atopic dermatitis) form a significant burden of disease. Knowledge of how the brain processes itch, that might occur uniquely for chronic itch populations, could be used to guide more effective psychotherapeutic interventions for these groups. To build the evidence base for such approaches, we conducted a series of coordinates-based fMRI analyses, to identify the shared neural mechanisms for itch across the published literature. Upon so doing, we identified a core "itch network" that spans the Basal Ganglia/Thalamus, Claustrum and Insula. Additionally, we found evidence that the Paracentral Lobule and Medial Frontal Gyrus, regions associated with cognitive control and response inhibition, deactivate during itch. Interestingly, a separate analysis for chronic itch populations identified significant recruitment of the Left Paracentral Lobule, potentially suggesting the recruitment of cognitive control mechanisms to resist the urge to scratch. We position these results in light of further integrative studies that could use neuroimaging alongside clinical studies, to explore how transdiagnostic psychological approaches-such as mindfulness and compassion training-might help to improve quality of life for individuals who experience chronic itch., (© 2024. The Author(s).)

Atopic dermatitis (AD) is a chronic inflammatory skin disease with a complex pathophysiology characterized by intense pruritus, often associated with psychological stress and atopic and non-atopic comorbidities that significantly reduce quality of life. The psychological aspects of AD and the interaction between the mind and body via the skin-brain axis have led to an interest in mind-body therapies (MBT). The aim of this article is, therefore, to reinforce the importance of psychodermatological care in AD. We performed a focused literature review on holistic practices or integrative MBT in AD, including education, cognitive behavioral therapy, habit reversal, meditation, mindfulness, hypnotherapy, eye movement desensitization and reprocessing, biofeedback, progressive muscle relaxation, autonomous sensory meridian response, music therapy, massage, and touch therapy. A multidisciplinary holistic approach with MBT, in addition to conventional pharmacologic antipruritic therapies, to break the itch-scratch cycle may improve AD outcomes and psychological well-being. Although there is a paucity of rigorously designed trials, evidence shows the potential benefits of an integrative approach on pruritus, pain, psychological stress, anxiety, depressive symptoms, and sleep quality. Relaxation and various behavioral interventions, such as habit reversal therapy for replacing harmful scratching with massaging with emollient 'plus', may reduce the urge to scratch, while education may improve adherence to conventional therapies.

Introduction: Atopic dermatitis is a complex, chronic, inflammatory skin disease that requires long-term control of symptoms like itch and sleep loss and improvement in quality of life, in addition to reduction of clinical signs. Lebrikizumab is a selective interleukin-13 inhibitor approved in the European Union, United Kingdom, United Arab Emirates, Canada, and Japan for treatment of moderate-to-severe atopic dermatitis in adults and adolescents. Here, we assess the magnitude of changes across signs and symptoms of atopic dermatitis with lebrikizumab monotherapy over the 16-week induction period in two phase 3 studies, ADvocate1 and ADvocate2., Methods: Eligible adults (aged ≥ 18 years) and adolescents (aged 12 to < 18 years and weighing ≥ 40 kg) with moderate-to-severe atopic dermatitis were randomized to receive either 250 mg of lebrikizumab or placebo subcutaneously every two weeks. Least squares mean percentage change from baseline through week 16 was compared between lebrikizumab and placebo using mixed model repeated measure analysis for the following endpoints: Eczema Area and Severity Index (EASI), Pruritus Numeric Rating Scale (NRS), Sleep-Loss Scale, Patient-Oriented Eczema Measure (POEM), and Dermatology Life Quality Index (DLQI)., Results: In both trials, significant (P < 0.05) improvements were observed for lebrikizumab treatment compared with placebo at each 2-week timepoint for EASI, Pruritus NRS, Sleep-Loss Scale, and POEM, and at each 4-week timepoint for DLQI, through week 16. Statistically significant (P < 0.001) improvements were observed at 16 weeks for lebrikizumab treatment versus placebo in ADvocate1/ADvocate2 for EASI (71.9%/75.0% vs. 35.6%/43.3%), Pruritus NRS (53.3%/46.3% vs. 21.4%/18.0%), Sleep-Loss Scale (57.7%/55.6% vs. 23.9%/25.5%), POEM (54.4%/45.8% vs. 18.8%/16.9%), and DLQI (64.2%/60.5% vs. 28.5%/32.2%). Patient photos show improvements in skin appearance when disease measures improve., Conclusions: Lebrikizumab monotherapy resulted in significant and fast improvements in multiple dimensions of disease (clinical signs, symptoms, and quality of life) over 16 weeks in patients with moderate-to-severe atopic dermatitis., Trial Registration: ClinicalTrials.gov identifiers, NCT04146363; NCT04178967., Competing Interests: Declarations. Conflict of Interest: Eric Simpson has received grants from or serves as Principal Investigator for: AbbVie, Amgen, Arcutis, ASLAN Pharmaceuticals, Castle Biosciences, CorEvitas, Dermavant, Dermira, Inc., Eli Lilly and Company, Incyte Corporation, Kymab, Kyowa Hakko Kirin, LEO Pharma, Pfizer, Regeneron, Sanofi, and Target RWE; and has received personal fees from: AbbVie, Amgen, Arena Pharmaceuticals, ASLAN Pharmaceuticals, Boston Consulting Group, Collective Acumen, Dermira, Inc., Eli Lilly and Company, Evidera, Excerpta Medica, ForteBio, Galderma, GlaxoSmithKline, Incyte Corporation, Janssen, Kyowa Kirin, LEO Pharma, Medscape, Merck, Pfizer, Physicians World, Regeneron, Roivant Sciences, Sanofi Genzyme, Trevi Therapeutics, Valeant Pharmaceuticals, and WebMD; Pablo Fernández-Peñas has served on advisory boards for: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squib, Celgene, Eli Lilly and Company, Janssen, LEO Pharma, Merck, Merck Sharp & Dohme, Novartis, Roche, Sanofi, and Sun Pharma; has given educational lectures for: AbbVie, Amgen, Avène, Eli Lilly and Company, Galderma, Janssen, La Roche-Posay, LEO Pharma, Merck, Novartis, Pfizer, Roche, Sanofi, Schering-Plough, Sun Pharma, and UCB Pharma; has conducted clinical trials for: AbbVie, Amgen, Arena Pharmaceuticals, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, CSL Behring, Dermira, Eisai, Eli Lilly and Company, Galderma, GlaxoSmithKline, Janssen, Jiangsu Hengrui Pharmaceuticals, Kyowa Hakko Kirin, LEO Pharma, miRagen, Novartis, OncoSec, Pfizer, Regeneron, Roche, Sun Pharma, UCB Pharma, and XOMA Corporation; Marjolein de Bruin-Weller has served as a consultant, speaker, advisor, and/or advisory board member for: AbbVie, Almirall, Arena Pharmaceuticals, ASLAN Pharmaceuticals, Eli Lilly and Company, Galderma, Janssen, LEO Pharma, Pfizer, Regeneron, and Sanofi Genzyme; Peter A. Lio has received grants as an investigator, honoraria for lecturing, and/or consulting fees from: AbbVie, AOBiome, Arbonne, Burt’s Bees, Dermavant, Dermira, Eli Lilly and Company, Exeltis, Franklin BioScience/Altus Labs, Incyte Corporation, IntraDerm, Johnson & Johnson, Kiniksa Pharmaceuticals, La Roche-Posay/L’Oréal, LEO Pharma, Menlo Therapeutics, National Eczema Association, Pfizer, Pierre Fabre, Realm Therapeutics, Regeneron/Sanofi Genzyme, Theraplex, TopMD, UCB Pharma, Unilever, and Verrica Pharmaceuticals; Chia-Yu Chu is an investigator, consultant, speaker, and/or advisory board member for: AbbVie, Amgen, Dermira, Eli Lilly and Company, GlaxoSmithKline, Janssen, Mylan, Novartis, Oneness Biotech, Pfizer, Regeneron, Roche, Sanofi, United BioPharma, and Viatris; Khaled Ezzedine is a consultant for AbbVie, Incyte, La Roche-Posay, Pfizer, Pierre Fabre, Sanofi, Eli Lilly and Company, and Almirall; Helena Agell is an employee of: Almirall, S.A.; Marta Casillas, Yuxin Ding, Fan Emily Yang, and Evangeline Pierce are employees and shareholders of: Eli Lilly and Company; Thomas Bieber is a speaker, consultant, and/or investigator for: AbbVie, Affibody, Almirall, AnaptysBio, Arena Pharmaceuticals, Asana BioSciences, ASLAN Pharmaceuticals, Bayer Pharmaceuticals, BioVersys, Boehringer Ingelheim, Bristol-Myers Squibb, Connect Biopharma, Dermavant, Domain Therapeutics, Eli Lilly and Company, EQRx, Galderma, GlaxoSmithKline, Glenmark Pharmaceuticals, Incyte Corporation, Innovaderm Research, IQVIA, Janssen, Kymab, Kyowa Kirin, L’Oréal, LEO Pharma, LG Chem, Merck Sharp & Dohme, Novartis, Numab, OM Pharma, Pfizer, Pierre Fabre, Q32 Bio, RAPT Therapeutics, Sanofi Regeneron, and UCB Pharma; and is Founder and Chairman of the Board of the non-profit biotech: Davos Biosciences. Dr. Bieber was affiliated with University Hospital Bonn, Bonn, Germany at the time of the study and is currently affiliated with Medicine Campus, Davos, Switzerland. Ethical Approval: Both trials were approved by the appropriate ethics review boards across approximately 100 study sites in the United States, Canada, Europe, and the Asia–Pacific area and were performed in accordance with the ethical principles of the Declaration of Helsinki and Good Clinical Practice guidelines. All patients provided written informed consent to participate in the trials. Patients provided written consent for use of their photographs for publication., (© 2024. The Author(s).)

Cisplatin-induced renal tubular injury largely restricts the wide-spread usage of cisplatin in the treatment of malignancies. Identifying the key signaling pathways that regulate cisplatin-induced renal tubular injury is thus clinically important. PARVB, a focal adhesion protein, plays a crucial role in tumorigenesis. However, the function of PARVB in kidney disease is largely unknown. To investigate whether and how PARVB contributes to cisplatin-induced renal tubular injury, a mouse model (PARVB cKO) was generated in which PARVB gene was specifically deleted from proximal tubular epithelial cells using the Cre-LoxP system. In this study, we found depletion of PARVB in proximal tubular epithelial cells significantly attenuates cisplatin-induced renal tubular injury, including tubular cell death and inflammation. Mechanistically, PARVB associates with transforming growth factor-β-activated kinase 1 (TAK1), a central regulator of cell survival and inflammation that is critically involved in mediating cisplatin-induced renal tubular injury. Depletion of PARVB promotes cisplatin-induced TAK1 degradation, inhibits TAK1 downstream signaling, and ultimately alleviates cisplatin-induced tubular cell damage. Restoration of PARVB or TAK1 in PARVB-deficient cells aggravates cisplatin-induced tubular cell injury. Finally, we demonstrated that PARVB regulates TAK1 protein expression through an E3 ligase ITCH-dependent pathway. PARVB prevents ITCH association with TAK1 to block its ubiquitination. Our study reveals that PARVB deficiency protects against cisplatin-induced tubular injury through regulation of TAK1 signaling and indicates targeting this pathway may provide a novel therapeutic strategy to alleviate cisplatin-induced kidney damage., (© 2024. The Author(s).)

Purpose: Psoriasis is an immune-related disorder characterized by silver scales, epidermis thickness, and itching. She-Chuang-Si-Wu-Tang (SSWT), a traditional Chinese medicine decoction, has been used clinically for 400 years. Although it benefits psoriasis treatment, the mechanism of action is still unclear. This study explores SSWT's molecular mechanism in treating psoriasis through network pharmacology analysis and experiments., Methods: We identified relevant SSWT and psoriasis targets using network pharmacology and conducted SSWT quality control with high-performance liquid chromatography (HPLC). A mouse model of psoriasis was established using imiquimod (IMQ), with the drug administered continuously for seven days, spanning an eight-day period. During the experiment, we observed spontaneous scratching behaviors and assessed the Psoriasis Area and Severity Index (PASI) scores. At the conclusion of the experiment, we examined skin tissue pathology under an optical microscope and measured epidermal thickness. Additionally, we used enzyme-linked immunosorbent assay (ELISA) and quantitative reverse transcription polymerase chain reaction (qRT-PCR) to measure interleukin (IL)-23, IL-17A, IL-17F, and interferon (IFN)-γ levels in the mice's serum and their mRNA expression in the skin. Western blot analysis was conducted to assess protein levels related to signaling pathways., Results: Results indicate that SSWT may target IL-17 signaling pathways and T helper (Th) 17 cell differentiation, as predicted by network pharmacology. SSWT significantly improved the PASI and Baker scores, reduced epidermal thickness, and decreased spontaneous scratching in IMQ-induced mice. Additionally, SSWT treatment significantly lowered the concentrations of inflammatory factors in the serum and skin lesions, as well as mRNA expression levels, compared to the IMQ group. Furthermore, SSWT significantly inhibited the phosphorylation of both the signal transducer and activator of transcription 3 (STAT3) and mitogen-activated protein kinase (MAPK) pathways., Conclusion: In summary, this study unveiled the potential anti-psoriatic mechanism of SSWT, offering new evidence for its clinical application., Competing Interests: The authors declare no competing financial interests or personal relationships that could influence the work reported in this paper., (© 2024 Chen et al.)

Recessive dystrophic epidermolysis bullosa (RDEB) is a rare genetic disease resulting from inadequate type VII collagen (C7). Although recurrent skin blisters and wounds are the most apparent disease features, the impact of C7 loss is not confined to the skin and mucous membranes. RDEB is a systemic disease marred by chronic inflammation, fibrotic changes, pain, itch, and anemia, significantly impacting QOL and survival. In this narrative review, we summarize these systemic features of RDEB and promising research avenues to address them., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Declaration of Competing Interest None.

Pruritus is a common complaint in dermatology outpatient clinics. It is defined as chronic pruritus if the symptoms last 6 weeks or longer. Fibromyalgia is a chronic, extensive pain syndrome that is well-known for its clinical signs, such as exhaustion, sleeping disorders, and some other pain symptoms. In the present study, it was investigated whether chronic pruritus patients were accompanied by fibromyalgia. The study included 100 patients with chronic pruritus and 100 controls without dermatological disease. All of the individuals were first evaluated in the dermatology clinic, and the patients having any musculoskeletal symptoms were then referred to a physiatrist in terms of accompanying fibromyalgia syndrome. Fibromyalgia was detected in 29 (29%) of 100 chronic pruritus patients and 6 (6%) of 100 patients in the control group. There was a statistically significant difference between the two groups regarding accompanying FM (p < 0.001). In the chronic pruritus group, pruritus severity, according to VAS and the four-item itch questionnaire score, was statistically significantly higher in patients with fibromyalgia than in patients without fibromyalgia (p = 0.027, p = 0.002, respectively). In addition, the number of patients with severe/very severe chronic pruritus was statistically significantly higher in the group accompanied by fibromyalgia (p = 0.023). It may be suggested that fibromyalgia is a frequent disease that can accompany chronic pruritus. Clinicians should keep in mind that there is a possibility of the coexistence of both diseases. This study calls attention to the complex relationship between chronic itch and pain., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Lichen planopilaris (LPP) and frontal fibrosing alopecia (FFA) are the most common causes of lymphocytic scarring alopecia. Itching of the scalp is a common accompanying symptom. The aim of the study was the clinical assessment of pruritus and its correlation with dermoscopic features. Methods: Sixty-one patients with scarring alopecia were analyzed (LPP = 16; FFA = 33; coexisting LPP-FFA = 12). Each patient underwent a trichoscopic examination. Itch severity and characteristics were assessed using a Visual Analogue Scale (VAS), 4-item Itch Questionnaire and 12-item Descriptive Pruritus Assessment Questionnaire. Results: Itching of the scalp occurred in 73.8% of the patients (mean maximal VAS 5.3 ± 3.1 points). Pruritus was most frequently accompanied by tingling (19.7%) or burning (14.8%) sensations. The following factors most frequently increased the severity of pruritus: sweating, heat, stress and hot water. On the other hand, cold water and cold air often relieved symptoms. There was a significant relationship between itch and perifollicular scaling ( p = 0.011), hair diameter diversity ( p = 0.008) and white halo ( p = 0.016). Conclusions: Pruritus was the main subjective complaint reported by patients suffering from LPP and FFA. A better understanding of pruritic features may help in the selection of an effective therapeutic strategy.

Chronic liver disease (CLD) is a significant contributor to global mortality. For people who are living with CLD, however, there is a substantial and often overlooked burden of physical and psychological symptoms that significantly affect health-related quality of life. CLD frequently presents with a multitude of interrelated and intricate symptoms, including fatigue, pruritus, muscle cramps, sexual dysfunction, and falls. Increasingly, there is interest in studying and developing interventional strategies to provide a more global approach to managing these complex patients. Moreover, in addition to established guidelines for the management of conventional complications, such as ascites and hepatic encephalopathy, there have been efforts in developing evidence-based guidance for the treatment of the more subjective yet still problematic elements. This review will address the management of these less "classical" but nonetheless important symptoms., Competing Interests: The authors disclose no potential financial or non-financial conflict of interests regarding this study., (© The Author(s) 2024. Published by Oxford University Press and Sixth Affiliated Hospital of Sun Yat-sen University.)

Previously, some allergic conditions involving pruritus have been linked to migraine, raising the possibility that migraine and itching may be governed by similar underlying mechanisms. We aimed to investigate the efficacy of Lasmiditan, a highly selective agonist of the 5-hydroxytryptamine 1F (5-HT1F) receptor and a recently approved medication for the treatment of migraine headaches, in ameliorating serotonergic itching. Forty animals were employed in the present study (n = 40). Eight animals were randomly assigned to each of the following study groups (n = 8, in each group): (1) "Normal Saline": This group was given intradermal injections of normal saline (2) "5-HT": The animals were injected with intradermal 5-HT, which was used to induce itching. (3) "Lasmiditan 0.3", "Lasmiditan 1", and "Lasmiditan 3" groups: injected with 5-HT as well as intraperitoneal Lasmiditan at different dose levels (0.3, 1, and 3 mg/kg, respectively). Scratching behavior was recorded for 60 min, and the skin tissue of three mice was sampled at the end of the behavioral experiment to assess the levels of TLR-4, IL-31, 5-HT1F receptor, CGRP & TRPV4. In the present study, we found that Lasmiditan when administered at 1 mg/kg effectively reduced serotonin-induced itching compared to the "5-HT" group (P < 0.0001). Following the administration of Lasmiditan (1 mg/kg), the expression levels of the 5-HT1F receptor significantly increased (P < 0.01). Further, the levels of TLR-4, IL-31, CGRP & TRPV4 were substantially reduced upon the administration of Lasmiditan (1 mg/kg). We found that Lasmiditan is effective in reducing serotonergic itch in mice through its interaction with the 5-HT1F receptor in the skin tissue of mice., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)