Q&A: Managing Chronic Itch With Renowned Investigator Gil Yosipovitch, MD

Gil Yosipovitch, MD, professor of dermatology, the Stifel Endowed Chair of medical dermatology, and the director of the Miami Itch Center at the Doctor Philip Frost Department of Dermatology at the Miller School of Medicine in Miami, opened his presentation titled "Managing Itch" at the 2025 Revolutionizing Atopic Dermatitis (RAD) Conference in Nashville, Tennessee, with this reminder. Moving on from what does not work for patients with moderate-to-severe AD, the session focused on the underlying mechanisms of chronic itch and the expanding toolkit of treatments that focus on the specific mechanisms underlying the condition.1

In an interview at the meeting with Patient Care,© Yosipovitch highlighted the main areas of the presentation keeping in mind the interests of primary care clinicians who are the first practitioners in most cases to see a patient with a flare of the disease and to initiate treatment. In the transcript that follows, he provides practical guidance on managing itch in atopic dermatitis: from barrier‑repair moisturizers and topical agents to biologics, JAK inhibitors, and neural‑targeted therapies. He also underscores the limited role of antihistamines, the risks of long‑term topical and systemic corticosteroids, and the importance of timely referral to dermatology.

Gil Yosipovitch, MD

Courtesy of Miller School of Medicine

The following transcript has been lightly edited for clarity and length.

Patient Care: You're often referred to as the “king of itch.” For a primary care audience, could you give a brief overview of the pathophysiology of itch? Just the essentials—what do they need to know?

Gil Yosipovitch, MD: Itch has many causes. Everyone experiences itch occasionally, but chronic itch is a disease state, much like chronic pain. It involves skin inflammation, neural activity, neural sensitization, and sometimes systemic or psychiatric components.

From a primary care standpoint, chronic itch can be related to inflammatory skin diseases—like atopic dermatitis, psoriasis, or urticaria—but it can also be a sign of systemic conditions, such as liver failure, kidney failure, or malignancies like lymphoma. There's also neuropathic itch, from nerve damage, and psychogenic itch, seen in conditions like depression, anxiety, or high stress.

PC: Central sensitization is a term used to describe a process underlying chronic pain. Would you explain the concept in the context of chronic itch?

Yosipovitch: Yes, exactly—very similar mechanisms are involved. We've done brain imaging studies showing that the same areas of the brain activated in chronic pain are also activated in chronic itch. Peripherally, there's also overactivation of sensory nerves. So in many ways, chronic itch mirrors chronic pain in how it affects the nervous system. You know, what many people don’t realize is that itch can be just as distressing as pain. Some patients even say they’d rather live with pain than chronic itch. In extreme cases chronic itch even leads to suicidal ideation.

PC: Would you highlight the medication classes you discussed during your presentation at RAD?

Yosipovitch: So, we discussed several therapeutic classes. There are the immune-targeting therapies that include drugs that inhibit type 2 cytokines, such as interleukin(IL)-4, IL-13, and IL-31. IL-31 is known as the "itch cytokine" because of its strong role in generating itch. Then there are neural targeting therapies, primarily the drugs that are used to treat neuropathic pain, like gabapentin and pregabalin, and also certain selective norepinephrine reuptake inhibitors (SNRIs) used at low doses. We also are learning about the most effective use of opioid receptor modulators: In chronic itch, there’s an imbalance between mu-opioid and kappa-opioid receptors—too much mu, not enough kappa. Kappa-opioid agonists (which antagonize mu activity) don’t reduce pain but do inhibit itch. This is a distinct and important class.

PC: Where should primary care physicians begin when initiating treatment for atopic dermatitis?

Yosipovitch: I would say start with the basics of good skin care because there is significant damage of the skin barrier in eczema. There are over-the-counter topical moisturizers now that have antipruritic and anti-inflammatory effects, for example CeraVe Itch Relief and Aveeno Itch Relief contain pramoxine, which is a low-potency topical anesthetic.

For prescription topical drugs of course there are topical steroids but the broad nonspecific effect on inflammation leads to well known long-term adverse effects; we really want to avoid using them or use them most sparingly.

There are several classes of nonsteroidal topicals now, with much more highly targeted mechanisms of action, including roflumilast and crisaborole, which are both phosphodiesterase-4 inhibitors and the newest one available, tapinarof, an aryl hydrocarbon receptor modulator.

Then, for more extensive disease, there a a number of biologic agents and some small molecules that specifically target the type 2 inflammation and neuroimmune signaling that underlie atopic dermatitis that we just talked about. The biologics most often used target IL-4, IL-13, IL-31, and include dupilumab, lebrikizumab, and nemolizumab, and tralokizumab. The other class of potent agents are the Janus kinase, or JAK, inbitors, such as abrocitinib and upadacitinib.

While primary care providers may not prescribe all of these, they should be aware of them.

PC: Antihistamines are still widely used in primary care for itch. Would you comment?

Yosipovitch: This is critical: oral antihistamines are essentially ineffective for the itch of atopic dermatitis; perhaps the sedating ones can be helpful with sleep, but the mechanism of itch in AD does not involve histamine.

So one of the key take-home messages for primary care is: Don’t rely on oral antihistamines for itch in AD. And also, avoid long-term systemic corticosteroids. Yes, they reduce itch quickly, but the side effect profile is extensive. They're a short-term fix with long-term risk.

PC: At what point should a primary care physician refer to a specialist?

Yosipovitch: I would say that when you feel you have exhausted topical treatment options and the patient still has significant itch, sleep disturbance, or poor quality of life, it’s time to refer to a dermatologist. Don’t keep trying medications that aren’t working—get them to someone who can escalate treatment.