Neuroimmune Dysregulation and Psychiatric Comorbidities in Chronic Pruritus: Pathophysiological Mechanisms and Emerging Multimodal Therapeutic Approaches

Chronic pruritus is a multifactorial clinical condition characterized by persistent itching and complex interactions among immune signaling, neuronal sensitization, psychological disturbances, and behavioral responses. Its clinical significance extends beyond cutaneous manifestations, frequently affecting sleep quality, emotional well-being, daily functioning, and overall quality of life. This narrative review aimed to analyze the neuroimmune mechanisms underlying chronic pruritus, examine its relationship with psychiatric comorbidities, and evaluate current multimodal therapeutic strategies from an international perspective, incorporating scientific contributions from Latin America. A qualitative, descriptive, and analytical approach was adopted to synthesize evidence from experimental investigations, observational studies, clinical trials, and international guidelines. The reviewed literature identified IL-4, IL-13, IL-31, and thymic stromal lymphopoietin as relevant mediators of neuroimmune communication, with signaling pathways involving JAK1, TRPV1, and TRPA1 contributing to sensory neuronal activation and hypersensitivity. Peripheral and central sensitization were associated with persistent sensory amplification and maintenance of the itch–scratch cycle. Psychiatric findings demonstrated clinically relevant associations with anxiety, depression, psychological stress, and sleep disturbances, although causal relationships remain incompletely established. Randomized clinical trials showed meaningful reductions in itch intensity following targeted inhibition of IL-4/IL-13 and IL-31 receptor signaling in patients with prurigo nodularis. Latin American evidence highlighted substantial symptom burden, quality-of-life impairment, and regional limitations in access to specialized healthcare. Overall, the findings support understanding chronic pruritus as a multidimensional condition requiring individualized assessment and coordinated dermatological, neurological, and psychological approaches. Further longitudinal and comparative investigations are necessary to clarify neuroimmune biomarkers, establish the clinical relevance of central sensitization, and determine the effectiveness of integrated multimodal interventions across different pruritic disorders.