Reaction of cutaneous blood vessels to successive insults: Repeated intradermal histamine challenge on normal and irritated human skin

Background: Histamine, a major mediator in endogenous and exogenous skin disorders, has been extensively investigated. Many experiments concern external provocation, yet the sequence of events as well as the influence of timing of the provocating factors require clarification. Objective: To document cutaneous reactivity to histamine rechallenge at different time points, as well as the response of irritated skin (irritant dermatitis) to histamine. Methods: Histamine was intradermally administered on the upper back of 20 volunteers at different time points to 3 sites and following SLS-induced irritant dermatitis to another site. The cutaneous vascular response was measured by laser Doppler flowmetry. Results: The response to a second prick when the first prick response had decayed to half its peak was significantly higher than all the other responses that resulted from a second prick (p < 0.01). The other responses did not significantly differ from each other or from the first prick response. When the histamine prick was performed over a 24-hour SLS patch, the response was greater than at all other sites (p < 0.01). Conclusion: An excitation state, at which the skin readily reacted to the second insult, may underlie the augmentation of the response to a histamine prick over the irritated skin. Irritation modulates cytokines, which may be the mechanism by which the response to histamine administration is enhanced. Tachyphylaxis did not occur at the time points tested, but may occur at longer intervals, necessitating further investigation.