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Background: The mechanisms for producing weals in chronic spontaneous (idiopathic) urticaria (CSU) are incompletely understood. Leucocyte infiltration with vascular leakage and expression of the potent vasoactive agents’ calcitonin gene-related peptide (CGRP) and vascular endothelial growth factor (VEGF) are features of late-phase allergic skin reactions, previously proposed as a model of CSU.

Objective: To measure CGRP and VEGF expression in lesional and non-lesional skin from CSU patients and to compare results with a control group.

Methods: Eight paired biopsies (one from 4–8 h spontaneous weals and one from unin- volved skin) were taken from eight patients with CSU and nine control subjects and stud- ied by immunohistochemistry and confocal microscopy.

Results: Lesional skin in CSU contained significantly more CGRP+ and VEGF+ cells than non-lesional skin. No significant differences were observed in CGRP and VEGF expression between non-lesional skin and controls. In lesional skin, VEGF and CGRP co-localised to UEA-1+ blood vessels. CGRP was also expressed by neutrophils and eosinophils and to a lesser extent by CD90+ fibroblasts, mast cells, CD3+ and CD68+ cells. CGRP and VEGF expression was not related to the duration of disease.

Conclusion and Clinical Relevance: Increased expression of CGRP and VEGF in lesional, but not uninvolved, skin indicates that these potent vasoactive agents may play a role in wealing and tissue oedema in CSU so representing novel targets in therapy.