The optimal management of itch

A recent review provides a timely update regarding what is known about skin barrier damage and itch. The review, which appeared online August 22 in Acta Dermatology Venereology, also discusses the benefits and risks of current treatments and highlights promising prospects in development.

It is widely known that dry skin occurs in different populations and diseases, and as part of the aging process, says lead author Gil Yosipovitch, M.D.

NEW: IL-4, IL-13 cause scratching in mice

"However, this review is timely because the last time there was a review published on this topic was almost 10 years ago," he adds. Dr. Yosipovitch is professor and director of the Miami Itch Center at the Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery at the University of Miami Miller School of Medicine.

During the past decade, much information about new topical options, particularly treatments for dry skin that could also help associated itch, has emerged, says Dr. Yosipovitch. "Everyone is giving emollients for dry skin. But sometimes, you must have, in addition, something that reduces the itch."

Supplementary ingredients can help target multiple components of the itch pathway. For example, cannabinoid-based topicals are a very hot topic, notes Dr. Yosipovitch. Studies have shown that incorporating an endocannabinoid-targeting component within a cream, such as N-palmitoylethanolamine, decreases itch sensation by boosting barrier lipid content. Although little research comparing specific preparations presently exists, he says, it's important for dermatologists to know that these drugs impact the skin barrier along with itch.

Similarly, Dr. Yosipovitch says, there's a lot of information available about ceramides and the skin barrier. But the review also emphasizes the role of skin pH in barrier damage. Specifically, elevated transepidermal water loss (TEWL) is a hallmark of the disrupted skin barrier associated with inflammatory skin diseases.

"These diseases are also associated with a higher epidermal pH, which activates proteases to promote stratum corneum turnover and desquamation," write Yosipovitch et al. Additionally, these proteases further activate protease-activated receptor (PAR)-2 nerves in the skin, causing itch.

RELATED: Interleukin-29 for inflammatory autoimmune diseases

Additionally, PAR activation leads to downstream activation of transient receptor potential (TRP) vanilloid 1 and ankyrin 1 (TRPV1 and TRPA1, respectively) ion channels in nerves. TRP cation subfamily M member 8 (TRPM8) channels are cold-gated ion channels that, when activated, inhibit both histaminergic and non-histaminergic itch sensory pathways. In two small studies, a lotion containing a novel TRPM8 cooling compound (menthoxypropanediol) significantly reduced pruritus.

Tapinarof, a naturally derived aryl hydrocarbon that reduces proinflammatory mediators including interleukin (IL)-17A and addresses skin barrier function, has been shown to reduce itch in mouse models and in vivo human skin studies of atopic dermatitis and psoriasis.

Topical tropomyosin receptor kinase A (TrkA) inhibitors inhibit the nerve growth factor (NGF) pathway; increased signaling via the NGF- TrkA-TRPV1 pathway is considered one of the mechanisms of cutaneous itch and a viable therapeutic target.

"Nerve growth factor is very important in the itch of psoriasis and possibly other conditions," says Dr. Yosipovitch. In a phase 2a/b psoriasis trial, the topical NGF inhibitor CT327 (Creabilis) has shown an antipruritic effect.

Topical polidocanol, a popular anti-itch product approved in Europe, targets non-histaminergic itch, which comprises the majority of chronic skin barrier-related itch, says Dr. Yosipovitch.

RELATED: Pay attention to pain caused by itch in atopic dermatitis

"I compound it for my patients," he says.

However, topical polidocanol is not commercially available in the United States.

Overall, says Dr. Yosipovitch, the review fills in blanks for both dermatologists and patients.

"Often we tell our patients, 'you have dry skin that's causing your itch.' But beyond that, we don't really discuss it. This review is a very good reference for practicing dermatologists to understand what's behind that dry skin that's causing itch, and what treatments are available and in development."

Disclosures:

Dr. Yosipovitch has been a consultant, advisory board member and principal investigator for Eli Lilly, Kiniksa, Menlo Therapeutics, Pfizer and Regeneron and Sanofi. He also has been a consultant and advisory board member for AbbVie, Bayer, Galderma, Novartis and Trevi Therapeutics. Additionally, he has been an advisory board member for CeraVe and Pierre Fabre, and a principal investigator for Sun Pharma.

References:

Yosipovitch G, Misery L, Proksch E, Metz M, Ständer S, Schmelz M. Skin barrier damage and itch: review of mechanisms, topical management and future directions. Acta Derm Venereol. 2019 Aug 22. doi: 10.2340/00015555-3296. [Epub ahead of print]