Meeting Report: Highlights of 12th World Congress of Itch

Highlights From The Plenary Sessions

The conference was opened by meeting chair Gil Yosipovitch of the University of Miami and the International Forum of the Study of Itch president Elke Weisshaar of the University Hospital Heidelberg in Germany. To kick off the highly anticipated 3-day event, Laurent Misery from France delivered the Jeffrey Bernhard Lecture. He discussed the frequently neglected burdens of pruritus compared with pain in the medical community. He presented his laboratory’s development of a model of reinnervated human skin that will help better study neurocutaneous interactions and pruritus.

Ethan Lerner from Massachusetts General Hospital gave the Yasushi Kuraishi Lecture titled “Life’s an Itch.” He emphasized the unmet needs of identifying therapeutic targets to treat chronic pruritus and highlighted his extensive work on mas-related G-protein coupled receptors as mediators of itch. Of note, he argued that there is still no antipruritic as effective as topical steroids despite growing advancements and drug development in the field.

Neuroscience of itch and pain

Allan Basbaum from the University of California, San Francisco reported a novel technique his group developed for assessing neurophysiology of spinal nerves in awake mice rather than the traditional imaging performed in anesthetized animals. The advantages of using awake animals enable us to assess the locomotion or lack of it in response to stimulus. Basbaum used this method to investigate the labeled line and polymodality properties of pain and itch, a topic that is impossible to adequately evaluate in anesthetized animals given limited spinal cord activity.

Rose Hill from Scripps has worked with 2021 Nobel Prize laureate, Ardem Patapoutian, on mechanically activated ion channels: PIEZO1 and PIEZO2. In her fascinating lecture, she demonstrated that mechanical itch has 2 different classes of pruriceptors, which sense mechanical stimuli in addition to pruritogens. The data demonstrate a role for PIEZO1 in somatosensory neurons, which has been overlooked owing to the well-known role of PIEZO2 in light touch and proprioception.

Neuroscientist Francis McGlone from Liverpool addressed the role of peripheral nerves in the mechanism of the itch–scratch cycle in his study on a unique patient with loss of dorsal root ganglia (DRG) of large nerves. Despite the lack of large myelinated fibers, the patient was able to perceive scratching as rewarding, supporting the hypothesis that scratching pleasurability is contributed to by small afferents C- and Aδ-fibers as opposed to Aβ.

Central mechanisms of opioid itch are well-studied; however, peripheral mechanisms are unclear. Xinzhong Dong from Johns Hopkins University sought to fill this gap in knowledge. He found that β-endorphin (βEND)– and DAMGO (a mu-opioid receptor selective agonist)-induced itch depends on μ-OR expressed by peripheral MRGPRA3+ sensory neurons. μ-OR agonism drove itch through Gq signaling but not Gi signaling. The contribution of βEND to psoriatic itch was demonstrated by decreased scratching bouts in a βEND-knockout mouse with imiquimod-induced psoriasis compared with that in a wild type.

Comparative itch

For the first time in the World Congress on Itch (WCI), a special session dedicated to comparative itch in animals was chaired by Santosh Mishra from North Carolina State and Frane Banovic from Georgia State. Studies on itch transcriptome and neuroimmune mechanisms were discussed by Banovic and revealed that the atopic dog is a close homolog to human atopic dermatitis (AD) and thus may be used to guide novel drug development. Chie Tamamoto-Michizuki from North Carolina State compared the DRG transcripts of select itch-signaling molecules among humans, cats, dogs, and mice. The results provide novel insight into the overlap in pruriceptive signaling across species, elucidating potential animal models for the study of itch in humans. Hans Jurgen Solinski from Heidelberg, Germany was awarded the Hermann Handwerker Prize for the best basic science presentation. He profiled pig DRGs and identified multiple marker genes that have functional associations with acute and chronic itch in mice and humans, laying the groundwork for the potential use of pigs as translational research models for itch.

New techniques to objectively assess itch

Lars Arendt-Nielson from Denmark, the former president of the International Association of Pain, gave a captivating talk on itch and pain in humans. He emphasized how these 2 entities utilize common peripheral and central pathways and mechanisms, suggesting that they are not entirely separate phenomena as previously thought. He noted that human, experimental, exogenous methods exist to provoke and assess histaminergic and nonhistaminergic itch. Furthermore, human surrogate models of itch sensitization may be proxies for processes such as neurogenic itch with central manifestations.

Dina Katabi from the Massachusetts Institute of Technology presented the next generation of smart wireless sensors that do not require application to the body to assess scratching and sleep. Using artificial intelligence, these cutting-edge, invisible sensors track patient movements by analyzing radio signals that bounce off patients’ bodies and can measure sleep stages and scratching activity with 80% accuracy. They are currently being utilized in clinical trials and have great potential to revolutionize the evaluation of scratching behavior, especially in children with AD.

Steve Xu from Northwestern presented a new, dual-functioning wearable called ADAM (advanced acousto-mechanic sensor). This device can help monitor nocturnal and daytime scratching with high accuracy and assess its effect on sleep quality in patients with chronic itch. A second impressive feature is its vibrating biofeedback capability, which can be used to reduce scratching behavior. The device has received clinical validation, and the Food and Drug Administration acceptance is anticipated by next year. This invention represents a novel way to study scratching patterns while providing therapeutic benefits.

Amy Paller from Northwestern discussed the challenges of assessing and managing itch in the pediatric population, specifically with regard to hereditary disorders such as ichthyosis and recessive dystrophic epidermolysis bullosa. She presented a newly validated Patient-Reported Outcomes Measurement Information System framework, which can better standardize the measurement of itch symptoms and impact in the pediatric population.

Nicholas West from Queensland, Australia discussed the use of a spatial biology platform, GeoMx, to examine the changes in immune and neural gene expression in patients with AD after treatment with dupilumab. He subsequently introduced CosMx, an emerging technology capable of spatial profiling on a single-cell level, allowing the identification of neuroimmune cell subtypes and cell–cell interactions in AD and other chronic itchy conditions.

New biomarkers

Santosh Mishra from North Carolina State University College of Veterinary Medicine presented his latest work on the peripheral role of brain natriuretic peptide (BNP) in skin inflammation associated with AD as well as the central role of BNP in chronic itch. In a mouse model, he found that total skin thickness, scratching behavior, and periostin levels were lower in BNP knockouts than in wild type, suggesting that BNP upregulates itch mediators and may serve as a promising new biomarker.

Mark Hoon from the National Institute of Dental and Craniofacial Research presented his work on the role of neuronal oncostatin M receptor (OSMR) in itch. He shows evidence that oncostatin M (OSM) is upregulated in immune cells in itchy skin diseases. Furthermore, OSM potentiates itch responses in vivo, and knockout of sensory neuron–specific OSMRs reduces inflammatory itch. These conclusions suggest that antagonizing OSMRs is a promising therapeutic strategy for reducing pruritus.

Wenqin Luo from the University of Pennsylvania presented a novel approach for single-soma deep RNA sequencing of human DRG neurons. He noted the identification of >9000 unique genes per neuron on average and 16 neuronal DRG types to date. Ultimately, he was able to generate an unprecedented neural atlas of potential anti-itch targets, greatly broadening the opportunity for drug development.

Yong Chen from Duke University studied the functional roles of TRPV4 in skin keratinocytes and sensory neurons across various types of itch. He found that the deletion of TRPV4 reduced scratching behavior in 3 distinct models. He also noted that levels of phospholipid lysophosphatidylcholine (LPC) in serum are correlated with itch intensity of liver disease in patients with primary biliary cholangitis and that LPC-induced itch is TRPV4 dependent. These exciting results provide evidence for the function of TRPV4 as a novel pruriceptor transient receptor potential and thus a potential target for itch treatment. In a subsequent talk, Won-Sik Shim from South Korea found that TSLP was increased in keratinocytes and contributed to dry skin and pruritus. This interesting conclusion suggests that TSLP may be targeted to manage dry skin–induced itch along with TRPV4.

Neuroimmune mechanisms of itch

Brian Kim from the Icahn School of Medicine at Mount Sinai led an innovative session on the neuroimmune regulation of itch. Ru-Rong Ji from Duke found that in a mouse model of cutaneous T-cell lymphoma (CTCL), there are associated hyperinnervations in the early phase (20 days after CTCL injection) and hypoinnervations in the late phases (days 40–60). Given that neuropathic itch and cognitive decline occur in the later phases, this conclusion contributes valuable information to the neuroimmune mechanism underlying CTCL symptoms. Isaac Chiu from Harvard Medical School presented groundbreaking information on the critical role of Staphylococcus aureus virulence factor V8 (SAV8) in inducing itch in AD. Importantly, SAV8 works on PAR1; thus, targeting PAR1 could be a novel approach to treat itch. Caroline Sokol from Harvard Medical School presented her laboratory’s work on allergic immunity and the role of ganglioside GD3 cells, a distinct epidermal γδ population, in releasing IL-3 and priming allergen-induced itch. She concluded that blocking itch may therefore decrease allergic sensitizations and suggested that the IL-3 pathway may be a possible therapeutic target.

In her talk titled “cough is the itch of the throat,” Jacky Smith from the United Kingdom made the case that cough is analogous to scratch; both are host attempts to urgently clear noxious stimuli. She explained that the neuronal pathway underlying pathological cough begins with excessive airway nerve activation, specifically of C-fiber chemoreceptors and Aδ-fiber mechanoreceptors, which are also involved in mediating itch sensation. The sensory fibers involved in cough and itch release neuropeptides when activated, leading to neurogenic inflammation. The overlapping aspects of itch and cough could provoke new perspectives in both fields.

Itch At The Bedside: Clinical Aspects

Macarena Tejos-Bravo was awarded the Kenji Takamori Prize for the best clinical presentation. Her study aimed to evaluate the effect of acute stress on the somatosensory profile in adults with AD using a quantitative sensory test and analyzing intraepidermal nerve fiber density (IENFD) from skin biopsies. The results showed that chronic lesions had sensory alterations and maladaptation to acute stress, potentially owing to impaired small fiber function and reduced IENFD.

In a session led by Shawn Kwatra from Johns Hopkins and Daniel Butler from the University of Arizona, we learned about the unmet needs of chronic itch. Kwatra emphasized the disproportionate impact of chronic pruritic conditions on patients with skin of color and the need for an improved understanding of AD clinical presentations in this patient population. Butler presented the key difficulties of treating chronic pruritus in older patients, including confusing nomenclature and lack of treatment data. Katja Fischer from Australia provided an update on the mechanisms underlying the intense itch associated with scabies, specifically the role of scabies mite excretory proteins, host keratinocytes, and mast cells. Given that current medication options are largely ineffective, it is of great interest to develop an improved approach to control itch in scabies.

Sonja Ständer from Münster, Germany directed an exciting session dedicated to Prurigo Nodularis (PN). She highlighted the revolutionary impact of the targeted drug, dupilumab, followed by the impressive results of recently completed phase III trials evaluating nemolizumab for the treatment of PN. Takashi Hashimoto from Japan then presented his study investigating the dominating signaling pathway in PN lesions using immunofluorescence staining. He demonstrated that the MAPK/extracellular signal–regulated kinase and Jak1 pathways could be involved in PN pathogenesis. Both of these pathways involve IL-31 signaling, allowing for a targeted therapeutic approach.

Timothy Berger from the University of California, San Francisco (UCSF) and Laurent Misery led a session on neuropathic itch. Sarina Elmariah from UCSF emphasized the importance of diagnostic evaluation, interval testing, and combination therapy when approaching neurosensory disorders. Lea-Sophie Stahl from Münster, Germany gave a talk on the newly developed core diagnostic criteria designed to differentiate notalgia paresthetica and brachioradial pruritus and improve the efficiency of management in the outpatient setting. Raphaele Le Garrec from the University of California, San Diego presented his laboratory’s work on ciguatera neuropathy. He concluded that the application of cefotaxime to a mouse cheek is an effective tool for studying the pathophysiology of major ciguatera symptoms, especially itch.

Novel Treatments And Trials

Martin Metz from Berlin, Germany presented the results of a phase 1b study on the use of barzolvolimab, an anti-KIT antibody that reduces skin mast cells, for the treatment of PN. A single dose was overall well-tolerated with clinically meaningful improvements in itch and healing of PN lesions at 8 weeks. These data support that mast cells play an important pathophysiological role in PN. Further research on barzolvolimab for the treatment of PN is indicated.

Tyler Beck from the Medical University of South Carolina sought to expand the clinical applicability of kappa-opioid agonists (KOAs) with an extended-release product. A peripherally selective peptidic KOA TP-2021 subdermal implant was comparable with intravenous (IV) difelikefalin and achieved supratherapeutic plasma drug levels in mice. These results suggest that a single administration of TP-2021 could potentially avoid the need for IV or frequent oral administration of difelikefalin.

Shelly Leibman Barak from Kamari Pharma in Israel presented results from a multicenter, phase 1b study in Germany that evaluated the safety and tolerability of KM-001, a novel selective TRPV3 inhibitor, in patients with lichen simplex chronicus itch. KM-001 demonstrated a favorable safety profile, and preliminary efficacy data showed a dose–response relationship, with pruritus reduction in females but not in males.

A session dedicated to itch in systemic diseases led by Andreas Kremer from Zurich and Cynthia Levy from Miami mainly focused on cholestatic itch. Binita Kamath from the Hospital for Sick Children in Toronto discussed the efficacy of ileal bile acid transporter (IBAT) inhibitors in treating childhood hepatic itch. Notably, 84% of patients with Alagille syndrome treated with IBAT inhibitor, maralixibat, experienced a meaningful itch reduction. She emphasized that IBAT inhibitors may even prevent or delay liver transplantation in these patients.

Kosuke Matsuda from the University of Toyama in Japan presented the novel gabapentinoid, mirogabalin, and its effect on itch in an AD mouse model. Mirogabalin acted on the ⍺2δ-1 subunit of voltage-gated calcium channel in the spinal dorsal horn, suggesting an antipruritic effect on chronic itch in AD. Thus, mirogabalin may be an effective treatment for human AD.

We are looking forward to the next WCI meeting chaired by Elke Weisshaar from Germany in October 2025.

Ethics Statement

This article did not involve human or animal studies and thus did not have an informed consent process.

ORCIDs

Gil Yosipovitch: http://orcid.org/0000-0001-6303-1822

Sarah G. Brooks: http://orcid.org/0009-0008-1015-1159

Rami H. Mahmoud: http://orcid.org/0000-0002-9322-7030

Conflict of Interest

GY has received grants from Sanofi, Regeneron Pharmaceuticals, Pfizer, Escient Health, Novartis, Eli Lilly, Celldex, and Kiniksa Pharmaceuticals. He is or has been an advisory board member for Abbvie, Escient Health, Eli Lilly, Galderma, LEO Pharma, Novartis, Pfizer, Pierre Fabre, Regeneron Pharmaceuticals, Sanofi, Trevitherapeutics, Vifor, Kamari, and GSK. The remaining authors state no conflict of interest.