Neuronal sensitization for histamine-induced itch in lesional skin of patients with atopic dermatitis

Objective: Lowered threshold of neurons (ie, neuronal sensitization) in atopic dermatitis was investigated by testing sensitivity to histamine. Design: Comparative study. Setting: A dermatological clinic and a research laboratory. Participants: Eighteen patients with atopic dermatitis (AD) and 6 patients with chronic plaque-type psoriasis as well as 14 healthy control subjects. Interventions: Histamine prick was performed in lesional and nonlesional skin of patients and in control subjects. Main Outcome Measures: Axon reflex flare and wheal were measured planimetrically, and the itch intensity was rated on a numerical scale (0-10). Results: In nonlesional skin of patients with AD, itch intensity and axon reflex flare were both significantly smaller compared with controls (mean SEM maximum itch, 1.5 +/- 0.3 vs 3.1 +/- 0.2 [P<.05]; mean SEM diameter, 12.3 +/- 2.0 vs 25.3 +/- 2.5 mm [P<.01]). In lesional skin of patients with AD, on the contrary, massive itch was provoked (maximum itch, 4.4 +/- 0.3), although flare was relatively small (diameter, 16.1 +/- 3.4 min). Itch ratings in patients with psoriasis were low both in lesional and nonlesional skin (maximum itch, 1.3 +/- 0.6 and 1.0 +/- 0.4, respectively). Conclusion: As the area of axon reflex flare is an indirect measure of activity in primary afferent neurons, our results suggest a decreased activation of peripheral pruriceptors; in patients with AD. The massively increased itch in lesional skin of patients with AD might therefore be based on sensitization for itch in the spinal cord rather than in primary afferent neurons. This sensitization does not appear to be simply based on skin inflammation because histamine-induced itch was not augmented in lesional skin of psoriasis.