Inflammation-associated itching perceived as more intense

A recent study showing that patients perceive inflammation-associated itch as more intense and qualitatively different than itch without inflammation suggests that dermatologists target inflammation in conditions such as atopic dermatitis (AD), says the study's lead author. Additionally, the different itch pathomechanisms involved in inflamed and noninflamed skin may provide separate therapeutic targets.¹

"As practicing dermatologists," says Marcus Maurer, M.D., "we often treat patients with chronic inflammatory skin conditions, and virtually all of these diseases are associated with itch." However, he says, itch is difficult for physicians to grasp because they cannot see it and frequently underestimate its impact on patients. He is a professor of dermatology and allergy and head of dermatological allergology at Charité – Universitätsmedizin Berlin.
Investigators enrolled 30 healthy Caucasian females between ages 18 and 60 years with no previous history of AD. First, patients were instructed to induce pruritus on healthy volar forearm skin by rubbing approximately 40 cowhage spicules on a 4 cm2 area using a gloved finger. Immediately post-challenge, investigators assessed pruritus every minute for the following 30 minutes, using a 10 cm visual analog scale. Patients also rated the type and overall intensity of pruritus characteristics they experienced.

Next, patients were instructed to induce inflammatory dermatitis through repeated application of sodium lauryl sulfate 2% to a defined area on both volar forearms for one week. This process produced mild inflammatory dermatitis (average score: 2.3 ± 0.1 on a scale of 0 to 10), mainly characterized by erythema. Additionally, mexameter, Tewameter (Courage + Khazaka) and corneometer measurements showed significant erythema and functional impairment in the inflamed skin.

Patients then repeated the cowhage challenge on the inflamed skin and rated pruritus here as approximately 5-8, versus approximately 3-5 on non-inflamed skin (p<0.0001). Moreover, maximum cowhage-induced itch intensity ratings increased from 4.1 ± 0.4 before induction of inflammatory dermatitis to 6.5 ± 0.5 afterward (p<0.0001). Patients also perceived the cowhage-induced pruritus as more burning and painful (p<0.01) in inflamed skin.

"Based on our results," says Dr. Maurer, "itch is more intense when the skin is inflamed. Second, itch in inflamed skin is different - more painful and burning - than in noninflamed skin. Our study therefore shows that skin inflammation impacts both the magnitude and the perception of itch." These factors may partly explain why pruritus is a major driver of quality-of-life impairment in patients with chronic inflammatory skin conditions such as AD, write Maurer et al.

The study is relevant for practicing dermatologists, he adds, because it underscores the interplay of inflammation and itch. "Our results suggest that itch is worse and different when patients with chronic skin diseases have inflamed skin. On top of this, our results suggest that itch in inflamed skin and itch in noninflamed skin involve different pathomechanisms, and that the development of treatment options for pruritic skin conditions should take this into account."

The trial also supports the superiority of cowhage as an experimental itch inducer compared to other stimulants such as histamine and substance P, which have not shown different itch intensities between normal and inflamed skin in healthy subjects.

"Histamine skin-prick testing (or intradermal injection) is a good model for urticaria, where the release of histamine from skin mast cells is a major driver of the development of itchy urticarial lesions," says Dr. Maurer. Conversely, cowhage induces itch through protease-activated receptors (PARs) and is believed to be a good model for the itch linked to AD. "Our study supports this notion: cowhage gave a consistently enhanced and different itch in inflamed skin compared with noninflamed skin. Patients with atopic dermatitis often report that the itch they experience in inflamed skin is more intense and painful."

Disclosures:

Disclosure: This study was partly supported by a research grant from Bayer. Dr. Maurer's work was supported by the Else Kröner-Fresenius Foundation.

References:

1. André F, Fluhr JW, Hawro T, Church MK, Maurer M, Metz M. Characterization of cowhage-induced pruritus in inflamed and non-inflamed skin. J Eur Acad Dermatol Venereol. 2019 Aug 16. doi: 10.1111/jdv.15871. [Epub ahead of print]