Think Outside the Traditional Toolbox to Treat Itch

ORLANDO — “Itch may not be as sexy as Mohs surgery or aesthetic procedures,” but treating it is important and meaningful to patients, particularly those who’ve found little relief previously, Shawn G. Kwatra, MD, said at the annual ODAC Dermatology, Aesthetic & Surgery Conference.

Chronic itch is common, with presentations that range from annoying to debilitating. There are many over-the-counter and prescription treatments patients can and likely have tried by the time they seek a dermatologist for help.

In doctors’ defense, it can be highly challenging to know which approach is optimal for each individual with pruritus, added Kwatra, associate professor of dermatology at Johns Hopkins University, Baltimore, Maryland.

Cooling agents, topical capsaicin, topical anesthetics like pramoxine 1%, various forms of lidocaine, strontium, opioid modulators like naltrexone, oral Janus kinase inhibitor (JAK) inhibitors, and medical marijuana are among some of the “outside the box” tools in Kwatra’s itch toolbox.

Often a Medical Puzzle

Frequently, patients come to the dermatologist complaining of itch, “but you don’t see much on their skin.” After a trial of antihistamines, and some topical steroids, the doctor might put up their hands and think: I tried, but I don’t know what else to do. “This actually happens a lot,” said Kwatra, who is also director of the Johns Hopkins Itch Center.

This means itch can frustrate providers as well. But for patients, the impact on their quality of life can be on the same level as recovering from a stroke or living with heart failure, Kwatra said. Finding relief for their itch is where “we can make a big difference for patients.”

Consider Cooling Agents

Many of these therapies are inexpensive and widely available. Cooling agents like menthol, camphor, or calamine can reduce activity of the transient receptor potential (TRP) channels in the skin associated with itch. This ion channel also senses temperature, pressure, and other sensations.

Another option is topical capsaicin, which works through the same ion channels. It binds to the TRPV1 receptors in sensory nerve fibers and causes desensitization. Initially, four to six applications a day are required to reduce itch. After that, patients can apply the medication less frequently. “You have to tell folks we know it’s going to work, but it’s going to burn a lot initially,” Kwatra said. “In real world practice, I’m not using it often.”

A 1.8% capsaicin patch, approved for treating postherpetic neuralgia, can be used to treat pruritus as well. “You put the patch on for one hour and you can have a true clinical response,” he noted.

Another option for itch relief, the topical anesthetic pramoxine 1%, “is probably underutilized for our patients,” Kwatra said. Pramoxine 1% works fast — as quickly as 2 minutes — and lasts up to 8 hours and is well-tolerated with low toxicity, he added. The agent is applied three to four times a day and relieves itch by reducing the transmembrane permeability of sodium ions on the skin. “This is something widely available and cheap.”

Lidocaine, another topical anesthetic, is available compounded, over the counter, and as a spray or patch. “I would be careful before you use high doses, like 10%” because of tolerability issues, Kwatra cautioned. He generally starts with lower concentrations.

Topical strontium is really interesting as a strategy, Kwatra said. Strontium is a soft, white metal that competes with calcium for receptor binding. There are over-the-counter formulations available as a scalp solution or lotion, which, he said, “are ways to go with more episodic itching.”

Topical oatmeal can also relieve itch in some patients. “There is actually some good scientific evidence for topical oatmeal preparations,” he said.

Steroid-Sparing Novel Topicals

Topical ruxolitinib (a JAK inhibitor approved for atopic dermatitis and vitiligo); topical roflumilast (a phosphodiesterase-4 inhibitor) and topical tapinarof (an aryl hydrocarbon receptor agonist), both approved for treating psoriasis; and the atopic dermatitis drug crisaborole fall into this category of topicals with potential for treating itch, he said, noting that use for treating itch is off label.

Off-label use of biologic agents are also possible treatment options for itch, dupilumab and tralokinumab, both US Food and Drug Administration (FDA)–approved for treating atopic dermatitis. Emerging agents that may prove useful for treating itch include lebrikizumab, nemolizumab, amlitelimab, and rocatinlimab, he said.

In terms of oral therapies, the FDA has approved two oral JAK inhibitors for atopic dermatitis, abrocitinib and upadacitinib, which could prove useful for itch as an off-label indication, according to Kwatra.

Naltrexone Off Label

An emerging therapeutic concept for treating itch is using an opioid antagonist like naltrexone. Morphine causes more itch, so the theory is a reversal agent might help reduce it. The challenge is that naltrexone only comes as a 50 mg tablet, “and I find the high dose makes people nauseous and vomit,” he added.

Don’t Forget Devices

He referred to a “great paper” that he said has been “totally overlooked,” published in 2001, which evaluated a device that stimulates C fibers in the skin to reduce itch. In the study, 19 patients used the device to treat local areas 20 minutes daily for 5 weeks. Punch biopsies of the affected areas were taken at baseline and after treatment. Mean itch ratings decreased from 78% to 42%, and the number of immunoreactive nerve fibers in the epidermis decreased by 40% at the end of treatment.

“Electrical neurostimulation is better for localized pruritus. There is limited case series evidence, but it’s something to think about,” Kwatra said.

He and his colleagues also have a case study in press that explored the use of injected botulinum toxin to relieve recalcitrant, chronic itch in a 65-year-old man “who failed everything.”

Kwatra is a consultant or advisory board member for AbbVie, Amgen, Arcutis Biotherapeutics, ASLAN Pharmaceuticals, Cara Therapeutics, Castle Biosciences, Celldex Therapeutics, Galderma, Incyte Corporation, Johnson & Johnson, LEO Pharma, Novartis, Pfizer, Regeneron, and Sanofi.

Damian McNamara is a staff journalist based in Miami. He covers a wide range of medical specialties, including infectious diseases, gastroenterology, and critical care. Follow Damian on X: @MedReporter.

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