Lice infestation is a common ectoparasitic condition in sheep and may cause pruritus, wool loss, skin damage, and impaired productivity. This study developed a topical total alkaloid solution from Sophora alopecuroides and evaluated its formulation characteristics, stability, dermal tolerance, field efficacy, and target-animal safety in sheep naturally infested with lice. Total alkaloids were extracted from S. alopecuroides seeds using single-factor experiments and orthogonal optimization. Dermal safety was assessed using Buehler sensitization testing in guinea pigs and skin irritation testing in rabbits. Clinical efficacy was evaluated after medicated bath treatment in naturally infested sheep. The optimized extraction procedure used 70% ethanol, an 8-fold solvent-to-material ratio, 0.1% cellulase, and three extractions of 120 min each. The optimized formulation contained 6.5% total alkaloids, 10.0% sodium dodecyl sulfate, and 8.0% ethanol. The preparation met predefined quality criteria and remained stable under stress, accelerated, and long-term storage conditions. No treatment-related sensitization or irritation was observed in laboratory animals. In sheep, lice reduction rates at D4 were 95.27%, 100%, 100%, and 100% in the low-dose, medium-dose, high-dose, and diazinon groups, respectively, and all treated groups reached 100% lice reduction at D17. No obvious hematological, biochemical, or histopathological safety signals were observed. These findings support the potential of this plant-derived topical preparation for managing natural lice infestation in sheep.

The twenty-fifth anniversary of the discovery of obeticholic acid (OCA) in 2027 offers an opportunity to reconsider its scientific contribution and clinical trajectory. First described in 2002 as 6α-ethyl-chenodeoxycholic acid, OCA helped establish the farnesoid X receptor (FXR) as a therapeutic target linking bile acid homeostasis to inflammation and fibrosis. This review follows the molecule from its discovery and early biological characterization through pharmaceutical development to the withdrawal of its primary biliary cholangitis (PBC) authorizations in the European Union and the United States. Clinical trials demonstrated biochemical efficacy in PBC and biopsy-defined fibrosis improvement in non-cirrhotic metabolic dysfunction-associated steatohepatitis but did not establish corresponding long-term clinical benefit. Pruritus, adverse lipoprotein changes, and hepatic safety concerns complicated treatment, while the COBALT confirmatory trial failed to verify benefit in its randomized analysis despite favorable external-control comparisons. This history highlights the distinction between pharmacological activity, surrogate responses, and patient benefit. It also raises questions about whether earlier prioritization of lower exposure and complementary therapies could have improved tolerability, without assuming that these strategies would have prevented withdrawal. OCA's legacy extends to subsequent FXR ligands and approaches emphasizing molecular selectivity, tissue distribution, and temporal control of receptor activation. Its experience supports continued FXR investigation while underscoring that therapeutic value requires sustained clinical benefit and acceptable safety.

Pruritus has long presented a diagnostic paradox in dermatology. Despite being among the most frequent patient complaints, it remains undervalued when unaccompanied by visible pathology. Bias toward visual cues in the field has often resulted in a tendency toward systematic neglect during clinical evaluation, and patients presenting with pruritus of unknown origin are frequently mischaracterized with factitious conditions. However, recent neuroimaging advances are revolutionizing our approach to pruritus by rendering central nervous system (CNS) itch pathways directly observable through functional magnetic resonance imaging (fMRI). Pioneering investigations have captured the neural signatures of centrally-originating pruritus, including socially-triggered, contagious itch and expectation-amplified itch through nocebo mechanisms. These studies reveal distinct brain activation patterns and have mapped core CNS-itch circuitry. Such neuroimaging capabilities hold promise for developing objective itch biomarkers, stratifying treatment candidates, and providing objective visual validation of patient-reported symptoms.

Traumatic scars and burn scar contractures can cause pain, pruritus, restricted motion, impaired limb function, and difficulty tolerating occupational or protective equipment. Laser-based treatment is increasingly used in rehabilitation, but outcomes remain heterogeneous and often emphasize appearance. This structured narrative review and descriptive evidence map used seven PubMed/MEDLINE search blocks completed on July 21, 2026. Two authors independently screened 898 unique records from 1,191 retrieved records. Reference checking and targeted full-text review supplemented the search; 50 sources informed the framework. Randomized evidence was outcome-dependent: early pulsed dye laser improved patient-rated scar quality in the primary Early Laser for Burn Scars analysis, without consistent observer-rated or quality-of-life benefit. Two within-patient fractional carbon dioxide laser trials reported selected symptom or scar-item improvements despite no significant Vancouver Scar Scale difference. Direct evidence for objective function and return to role remained limited. We propose a minimum-plus-modules framework covering scar characteristics, symptoms, regional function, treatment burden, equipment tolerance, safety and downtime, and graded return-to-work or return-to-duty status. Assessments are linked to baseline, treatment sessions, interim review, treatment completion, and three- and six-to-12-month follow-up. The framework integrates established measures into a practical schedule; it is not a validated core outcome set and requires prospective evaluation.

Darier disease (DD) is a chronic disorder of keratinization characterized by pruritic keratotic papules and plaques in seborrheic areas, for which effective treatment options remain limited. To describe the preliminary outcomes of combination therapy with cyclosporine and isotretinoin, we retrospectively reviewed the medical records of three patients with clinically and histopathologically confirmed DD. Outcomes included changes in cutaneous lesions, pruritus visual analog scale (VAS) scores, and Dermatology Life Quality Index (DLQI) scores, as well as adverse events, laboratory findings, and the post-treatment clinical course. All three patients showed clinical improvement in cutaneous lesions and pruritus, with reductions of 6-7 points in pruritus VAS scores and 10-14 points in DLQI scores from baseline to treatment completion. After treatment discontinuation, no clinically apparent relapse occurred during follow-up periods of 9, 4, and 3 months in Cases 1, 2, and 3, respectively. Mild adverse events included cheilitis, alopecia, and xerosis; transient mild laboratory abnormalities were also observed, and no serious adverse events occurred. In this small retrospective case series, cyclosporine plus isotretinoin was associated with clinical improvement and acceptable short-term tolerability. Larger studies with longer follow-up are needed to evaluate the efficacy and safety of this combination.

Impact of nutrition on systemic health is well-recognized but the specific sensors that couple western dietary lipid metabolites into the pathological triggers of chronic itch and inflammation remain elusive. Here, we identify a metabolic- to-sensory axis in which 9-keto-12,13-epoxy octadecenoic acid (EKODE), an endogenous dietary linoleic acid derivative acts as a potent ligand for the G protein-coupled receptor 35 (Gpr35) to drive chronic itch, inflammation, and heat hypersensitivity. We demonstrate that Gpr35 is selectively expresses in a distinct population of sensory neurons and genetic ablation of Gpr35 in sensory neurons attenuates EKODE and psoriasis-associated itch and inflammation. Furthermore, pharmacological inhibition of Gpr35 significantly attenuates itch in mouse models of psoriasis and atopic dermatitis. We show that Gpr35 signaling engages the itch-specific brain natriuretic peptide, defining a labeled-line pathway that is functionally distinct from classical nociceptive circuits. Collectively, our findings establish Gpr35 as a critical neuro-metabolic sensor in healthy and disease conditions.

Itch and inflammation in atopic dermatitis (AD) have long been read as two parallel outputs of a single disease process. That framing sits awkwardly with the anatomy. Cutaneous sensory neurons and immune cells sit side by side in the skin and speak a shared language of ligand-receptor pairs. We recast that interface here as a bidirectional regulatory network, not a one-way road running from inflammation to itch. Going in one direction, type 2 and innate cytokines act straight on sensory neurons as pruritogens, each through its own receptor and signalling route. Going the other way, neuron-derived mediators such as substance P, VIP and NGF reshape how immune cells are recruited, polarized and how tissue is remodelled. Put together, the two arms form a feed-forward loop. Scratching, barrier disruption, cutaneous dysbiosis and central sensitization all feed one another. Within this framework, several counter-regulatory mechanisms have also been identified, including the capacity of CGRP to restrain type 2 immunity and the immunomodulatory functions of IL-31 that extend beyond its pruritogenic role. What the circuit does, then, hinges on how the work is split among sensory neuron subsets and on the state of each node, rather than on any linear cascade. Seen through this lens, today's and tomorrow's therapies-dupilumab, tralokinumab, nemolizumab, JAK inhibitors and kappa-opioid agonists-each land on a specific node of the circuit. The picture helps make sense of treatment-resistant itch and argues for rational, combination targeting of the circuit.

Many external and internal factors can affect skin lipid synthesis and composition, which may impair skin barrier function, and potentially cause skin dryness, pruritus and other sensory symptoms. Pruritus, frequently associated with xerosis-particularly in inflammatory skin diseases, such as atopic dermatitis (AD)-is a commonly reported dermatological symptom in the general population. This narrative review, based on conference proceedings from clinicians and dermatologists, discusses the clinical and psychological impact of pruritus on individuals experiencing this subjective symptom. Starting with a summary of the key mechanisms involved in the itch-scratch cycle and signaling pathways shared with pain sensation, this review highlights the significant impact of chronic pruritus and associated symptoms, including sleep disturbances, on quality of life (QoL) and mental health. One of the main conclusions emerging from discussions between experts was that pruritus is a symptom with strong psychological features, which can easily become chronic under stressful conditions, and significantly affect patients' daily life and well-being. Therefore, the psychological issues associated with chronic pruritus, such as anxiety and depression, must not be overlooked, and dermatologists should perform a general psychodermatological assessment of patients with chronic pruritus for effective management of their dermatological and underlying psychological symptoms according to current guidelines. Management options need to include supportive skincare products and medical approaches to relieve symptoms of skin barrier dysfunction and chronic inflammation, as well as holistic strategies to help manage the psychological consequences of chronic pruritus. If concomitant psychopathologies are diagnosed, tailored drug treatments should be considered on a case-by-case basis to adequately address them.