Pruritus (itch) is defined as an unpleasant sensation provoking the urge to scratch and can be understood both as a symptom and, when lasting more than six weeks, as a disease entity termed chronic pruritus (CP). CP is characterized by complex neurobiological changes and can persist independently of the initial trigger, significantly impairing quality of life. Advances since the 1990s in understanding itch pathophysiology have led to the development of numerous targeted therapies, although many treatments remain off-label. Pruritus is classified into dermatological, systemic, neuropathic, and psychogenic categories, often with overlapping etiologies. Effective management prioritizes identifying and treating the underlying cause. Pathophysiologically, itch originates from specialized peripheral sensory neurons (pruriceptors), which transmit signals through histaminergic and non-histaminergic pathways. While histamine plays a role mainly in urticaria, chronic itch is largely mediated by non-histaminergic mechanisms involving cytokines, neuropeptides, proteases, transient receptor potential (TRP) channels, and Mas-related G-protein-coupled receptors (MRGPRs). Keratinocytes, mast cells, and immune mediators such as IL-31, IL-4, and IL-13 actively participate in itch signaling, creating neuroimmune feedback loops. Peripheral and central sensitization, spinal disinhibition, and altered pain-itch interactions sustain chronic itch and the itch-scratch cycle, particularly in chronic prurigo (CPG), a distinct disease model for CP. Therapeutic strategies target multiple levels of itch processing. Traditional treatments include antihistamines, topical anesthetics, calcineurin inhibitors, antidepressants, gabapentinoids, and immunosuppressants, though efficacy varies. Recent breakthroughs include biologics targeting TH2 pathways (dupilumab, nemolizumab), JAK inhibitors, κ-opioid receptor agonists (difelikefalin), and IBAT inhibitors (for cholestatic pruritus). Novel targets under investigation include MRGPRs, PARs, KIT receptors, OX-40, and sodium channels.

Keloids are benign skin tumors resulting from deregulated wound healing processes, characterized by fibroblast hyperactivity, increased collagen deposition, and resistance to apoptosis. These lesions extend beyond the original wound borders and often cause significant physical and psychological burdens, including pain, pruritus, and reduced self-esteem. Despite advancements in medical science, keloid management remains a challenge due to the lack of standardized treatment protocols and the high recurrence rates associated with many therapeutic options. This review examines the efficacy and limitations of existing treatment modalities, including silicone gel sheets, antifibrotic agents, intralesional injections, cryotherapy, radiotherapy, laser therapies, surgical excision, and combination therapies. Emerging approaches, such as botulinum toxin, antihypertensives, platelet-rich plasma, and others, are also discussed. This article underscores the need for large-scale, high-quality studies focusing exclusively on keloids to refine treatment algorithms and advance therapeutic strategies.

Anti-EGFR monoclonal antibodies (mAbs)--cetuximab, panitumumab, and necitumumab--are cornerstone therapies for selected solid tumors but are frequently associated with cutaneous adverse drug reactions (ADRs). This study aimed to characterize and compare the dermatologic safety profiles of these agents using large-scale post-marketing pharmacovigilance data.

Pruritus might be a debilitating symptom in myeloproliferative neoplasms (MPN). Since mast cells (MC) play a pivotal role, we hypothesized that bone marrow (BM) MC contribute to the cause of pruritus. In this exploratory study, untreated MPN patients were included. BM aspirate/biopsy/blood and MPN-SAF questionnaires were obtained. Thirty-two patients were included (Essential Thrombocythemia n=19, Polycythemia Vera n=7 and Primary Myelofibrosis n=6). Eleven had clinically significant pruritus (35%). The absolute MC count and proportion/total nucleated BM-cells were significantly higher in patients with pruritus compared to those without (mean 25.5 vs. 58.1 MC/mm2, p 0.032, and 0.59 vs 1.66%, p 0.041, respectively). The MC immunophenotype and serum levels of tryptase, IL-6, TNF-α and sCD117 were not correlated. The absolute and relative MC numbers are increased MPN patients with pruritus. Whether MC play a pathophysiological role in causing pruritus, or are bystanders remains to be determined.

Background: With the increasing widespread use of GLP-1 RA and dual GIP/GLP-1 RAs in the treatment of obesity, their safety profile remains a concern for healthcare professionals (HPs). Objective: This study aimed to characterize and evaluate safety data from the EudraVigilance (EV) database for semaglutide (SEM), liraglutide (LIR), and tirzepatide (TIR). Methods: A hierarchical pharmacovigilance approach was applied, integrating SOC- and PT-level analyses with SmPC-based evaluation and both frequentist (ROR, 95% CI) and Bayesian (IC025) disproportionality methods. Within each molecule, reporter type-stratified analyses were performed, while across all molecules, disproportionality analyses were conducted separately in HP reports and in the full database to identify reporting patterns and potential safety signals, including those not described in the SmPCs. Results: Some ADRs, listed in the SmPC of only one or two of the three GLP1-RAs were also reported in the EV database for the other agents whose SmPCs do not specify these ADRs including optic ischemic neuropathy (TIR: 0.28% and LIR: 0.17%), alopecia (LIR: 0.81%), headache (TIR: 2.51%), intestinal obstruction (TIR: 1.55%), angioedema (LIR: 0.19%), hypersensitivity (SEM: 0.58% and LIR: 0.73%), etc. Pancreatitis, in particular, showed a significant but low-magnitude signal, being more frequently reported by HPs compared with non-HPs across all three GLP1-RAs. Additionally, statistically significant signals (IC025 > 0) were observed in both the HPs and full datasets. For example, for SEM vs. TIR, signals were identified for optic ischemic neuropathy (0.17; 0.13), gallbladder disorder (0.09; 0.11), and dysesthesia (0.42; 0.43), respectively. For TIR vs. SEM, signals were observed for injection site erythema (0.05; 0.11), injection site pruritus (0.01; 0.11), and injection site reaction (0.02; 0.08). Conclusions: These findings suggest potential safety signals beyond current SmPC information, emphasizing the need for continuous pharmacovigilance and cautious interpretation of reporting biases.