Free of lesions but not healthy -- The skin of patients with atopic dermatitis is primed for itch and inflammation.

Background: Atopic dermatitis (AD) is a highly prevalent inflammatory skin disorder characterized by episodic exacerbations and remissions. Why the clinically healthy skin of AD patients becomes rapidly inflamed and very pruritic, is poorly understood. Methods: Patients with AD, psoriasis, and chronic spontaneous urticaria (CSU) as well as healthy control subjects (n = 20 each) were assessed for differences in itch parameters, neurogenic flare reaction, and local blood flow responses to skin provocations with cowhage and histamine. Skin biopsies were obtained to assess expression of protease-activated receptors 2 and 4 (PAR-2, PAR-4), histamine H1 and H4 receptors (H1R, H4R), and mast cells. Results: Provocation of non-lesional skin of AD patients with cowhage resulted in prolonged itch (P = 0.020), which was not observed in psoriasis and CSU. Significantly prolonged and more intense cowhage- and histamine-induced itch (for duration, peak, and overall intensity) was also observed in lesional AD skin. Diminished neurogenic flare reaction and blood flow after histamine provocation were shown in AD and psoriasis patients. Non-lesional AD skin along with lesional AD and psoriasis skin showed an increased expression of PAR-2 and PAR-4, H1R and H4R. Mast cell number was higher in lesional AD and psoriasis skin (P = 0.006 and P = 0.006, respectively). Conclusion: The non-lesional skin of AD patients markedly differs from healthy skin in cowhage-induced itch responses and the expression of receptors for proteases and histamine. Proactive therapeutic interventions that downregulate these receptors may prevent episodic exacerbation in AD.