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Itch may be more complex than it seems. A recent literature review presents a range of causes and treatments for chronic pruritus, including more novel options and a disease schematic for clinical decision support.

The review has been published in by a multicenter team of dermatologists and leading pruritus researchers. It encompassed 45 studies, including 12 randomized clinical trials.

According to the research team, itching is the chief concern in about 1% of all physician visits. While many cases of chronic pruritus are relatively straightforward, with first-line topical therapies like hydrocortisone often proving sufficient for treatment, approximately 15% of cases have other causes including systemic diseases with secondary itch. Some chronic pruritus cases stem from multiple causes, authors wrote.

Paper first author Daniel Butler, MD, is an associate professor with University of Arizona College of Medicine and director of the college's Inflammatory and Aging Skin Research Program. He spoke with the Reading Room about the most current knowledge around chronic pruritus. The exchange has been edited for length and clarity.

How did the idea for this review originally come about, and what was its key objective?

Butler: This group of researchers is a team I consider itch royalty. They've been changing our perceptions of this disease for at least the last decade.

I feel like recently people have started to understand that this is a topic that clinicians should know more about. It's definitely an area where we can make a difference.

We wanted to provide something that is up to date on the pathophysiology of itch and how to treat it. We also provide a new disease schematic to help make it easier to approach this. There are a lot of things that people perceived about itch that really have been disproven in just the last five to 10 years. This review was our way of developing a new, easily capturable model to address this common presentation.

You mentioned older and changing perceptions. What are some of these older perceptions, and what's the impact of recent advances in pruritus knowledge?

Butler: If you go to most providers and say that you're itchy, you're probably going to get an antihistamine. But what we've found is that histamine is only involved in a small percentage of all itch patients. So this connection of antihistamines and itching needed to be debunked.

What we needed to do was really understand the pathways involved. It was once thought that all itch would have its own pathway. If you were clever enough or knew the right lab tests or could see something in the skin, you could determine whether this person's itch was caused by the immune system or dry skin.

What we've found, however -- and what this new disease schematic tells us -- is that it's likely a mixture of these. It gets us into this idea that there are likely overlapping etiologies involved. And that can open up different treatment opportunities.

How was this schematic designed and how specifically is it intended to help clinicians?

Butler: The new schematic is basically helping people understand these overlapping etiologies. The two chief ones we think of now with itch are either the immune system or an aberrant response in the nervous system, specifically the cutaneous nervous system.

Nerves and the immune system often are the contributors, but a lot of the time we see an overlap of both. You can treat both of them, sometimes easily. Instead of thinking "if I have the right treatment, this person's itch will go away," it's more about thinking "okay, how much overlap is this patient experiencing?"

For example, one patient may need an oral or injectable agent to control the immune system, but only a topical agent to control the nervous system. The reverse can also be true: Sometimes a little bit of topical steroid can help with immune system overactivity, but you may need an oral medication for the nervous system -- something like gabapentin or doxepin. When we use these agents by themselves they're not great, but when you combine them with other things you can get better effectiveness.

Our schematic can drive all of that etiological workup. It's a way of helping people approach this really complex symptom.

What does the foreseeable future hold for treating chronic pruritus?

Butler: One of the areas that I'm most excited about is getting better access to medications for patients with chronic pruritus. If you look at the medications currently approved by the [FDA] for chronic pruritus, it's a big zero -- despite the fact that it's one of the most common symptoms people come in with.

Itch has been neglected by our regulatory system because it's thought to be a secondary manifestation. A primary diagnosis of chronic pruritus doesn't translate into access to a lot of medications, and that becomes a problem. So one key goal is really substantiating chronic pruritus and having targeted medications for it.

Number two, a lot of people are working on gaining a better understanding of the pathophysiology of itch, because that's going to allow us to target the immune system and the nervous system much more effectively. The dream one day is to do a biopsy or a blood test to be able to see, for example, "how aberrant is this cutaneous nerve?" And once we're able to do that, we can be more targeted with our treatments.

Do you have a bottom-line takeaway for dermatologists?

Butler: Dermatologists really have a strong ownership of this patient population. What dermatologists may have experienced with this patient population 10 years ago, even five years ago, is not the same experience that they can have now.

When I started my career in dermatology about 20 years ago, a patient with chronic itch could cause eye-rolling. A lot of that was because we didn't have a great understanding of our options and didn't have a lot of options to begin with. But now we're growing our optionality. We have a lot more tools for this patient population, and a lot better understanding. For any dermatologist, any researcher, there are avenues to approaching these patients.