Abstract
ABSTRACT
Chronic spontaneous urticaria (CSU) is a mast cell‐driven inflammatory disease frequently accompanied by anxiety, depression, sleep disturbance, fatigue, and impaired quality of life. Pruritus, disturbed sleep, psychosocial burden, and treatment‐related effects are established contributors to this neuropsychiatric and functional burden. Whether immune‐to‐brain signalling provides an additional mechanism in a susceptible subgroup remains unknown. This hypothesis‐driven narrative review examines the blood–brain barrier (BBB) as one potential interface linking CSU‐associated inflammation to central effects. CSU studies report systemic inflammatory, vascular, and neuroimmune signals, including cytokine signatures, circulating matrix metalloproteinase‐9, and substance P–MRGPRX2‐related findings. Their potential neurovascular relevance is inferred from experimental or other disease settings rather than demonstrated in CSU per se. Our targeted search identified no human CSU studies assessing regional BBB permeability with dynamic contrast‐enhanced magnetic resonance imaging or tracer methods, blood–cerebrospinal fluid barrier function with the albumin quotient, serum S100B, or brain endothelial tight‐junction integrity, including claudin‐5 or occludin. Structural and functional neuroimaging findings in CSU do not establish barrier dysfunction. Systemic mastocytosis provides comparative evidence for mast‐cell‐related neuropsychiatric manifestations, although barrier involvement remains unproven. We therefore propose neurovascular alteration as a testable, non‐exclusive risk modifier whose relevance to CSU pathophysiology and psychiatric symptoms remains to be established.