• Topical treatments, phototherapy, and systemic (oral or injected) medications are used to treat prurigo nodularis (PN).
• It can take a combination of therapies to improve symptoms.
• One drug was recently approved to treat prurigo, and more effective, targeted treatments are in development now.

Prurigo nodularis is an intensely itchy, inflammatory skin disease that can be challenging to treat. It may take time to find the right treatment (or combination of treatments) to help you manage symptoms of intense itching and dome-shaped bumps. It’s important to understand all of the treatment options available to you, along with their limitations.

To get answers about PN treatment, MyPrurigoTeam spoke with Dr. Shawn Kwatra, associate professor of dermatology and director of the Johns Hopkins Itch Center in Baltimore. Dr. Kwatra treats people with PN and pursues research to better understand how this chronic skin condition develops.

What makes prurigo nodularis so difficult to treat?

One of the main challenges in treating PN is proper disease recognition. The disease can oftentimes be confused with a variety of other conditions.

Another hurdle to treating patients appropriately is understanding when is the right time to initiate which therapy. There haven’t actually been many well-controlled studies in PN, and much of our literature is based on either limited case studies or small studies. So it’s hard to get great recommendations on the best way to manage a PN patient.

Another issue with treatment is that the disease can be extremely heterogeneous [showing up differently in different people]. In some folks, PN can have nodules that are very shallow or ulcerated. And in other cases, oftentimes in patients with skin of color, there can be very large, firm nodules that are incredibly thickened and difficult to treat.

Which treatments are currently available for people with prurigo, and what are their limitations?

There are topical treatments, such as topical steroids. There’s also phototherapy, which is light therapy. And finally, there are several systemic agents [which can have effects throughout the body]. These are immune-modifying agents, such as methotrexate, cyclosporine, or other biologics that are off-label. [Drugs prescribed off-label are not approved by the U.S. Food and Drug Administration (FDA) for that condition or use.]

[Since the time of the interview, dupilimab (Dupixent) has been approved by the FDA to treat adults with prurigo nodularis. Dupilimab, an immune-modifying systemic drug known as a biologic, must be injected under the skin every other week.]

And there are neuromodulating agents, drugs that can reduce the transmission [of itch signals via nerves], things like gabapentin or pregabalin.

Limitations of Topical Treatments

Topical steroids are less effective in prurigo compared to other conditions because the firm nodule has a layer of dead skin and also thickened epidermis. It’s hard to penetrate through, which is one of the reasons topical steroids just, frankly, don’t work that well.

Limitations of Phototherapy

Some of the downsides are just about convenience. You have to go into a phototherapy unit two or three times a week and wait a very long time to see an effect. Oftentimes it can be even six to eight weeks, and [relief] is incomplete. So to be honest, I would rarely do phototherapy alone in the management of PN patients. I sometimes do it in combination with another agent.

Limitations of Systemic Treatments

Many of the immune-modulating agents need frequent lab monitoring [such as blood tests] because they can affect liver function or kidney function or cause hypertension or anemia. Some are not long-term options for these reasons.

Neuromodulating agents, like gabapentin or pregabalin and some antidepressants, are used to help take the edge off itch, but they don’t have immune-modifying capabilities. They can be drowsy, sedating, and increase the risk for falls. So I try to stay away from prescribing some of those medications.

For especially difficult cases that are not responding to conventional therapy, there are drugs such as thalidomide, which is an incredibly toxic drug that can lead to sensory issues, even embolism [a potentially fatal blood clot]. So in these patients, we have to monitor [with blood tests] very frequently.

It shows how many of the treatments that are currently available are truly not hitting the mark, and highlights the need for emerging therapies that are safe, effective, and — most importantly — targeted.

When do you recommend people move on from topical treatments and try systemic medications?

I recommend that people move on from topical therapy if they have diffuse involvement over a large body surface area and have inadequate response to topical therapy. I usually give topical therapy a chance on its own only in situations where the disease is incredibly localized — for instance, to one or two limbs or less than 10 to 20 nodules.

Disease severity is another important consideration when deciding about topical therapy. These areas can be very thickened, so there’s even less penetration of the topical steroid into those itchy nodules.

In my view, topical agents for PN are an adjunctive therapy, [best used] along with a systemic agent. We’ve found that two-thirds of patients have itch in the nodules and in the intervening normal-appearing skin. That’s important evidence that the disease is truly systemic. You can’t only treat the nodules, you’ve got to treat the wider body surface area, the systemic inflammation. So systemic treatments are needed early on in therapy.

If prurigo is associated with an underlying disease, does treating that disease cure PN?

There’s a variety of [conditions] that can be associated with prurigo nodularis, like type 2 diabetes, chronic kidney disease, and HIV. But the question is, are these things making folks have prurigo? That’s not necessarily true.

We’ve had folks who’ve gotten their diabetes under control, and they still had the prurigo. We’ve actually found that patients who are diagnosed with prurigo nodularis are more likely to have progression of chronic kidney disease and other disease comorbidities [additional health conditions]. So it could actually be that the underlying inflammation of PN is worsening these other diseases.

What should people with PN know about treating the condition?

PN patients should know that their condition is due to specific elements of neural [nervous system] and immune dysregulation. In recent years, we are understanding much more about the pathogenesis [how PN develops], and we have more tailored treatments that are becoming available. If you’re a patient that has PN, and you’ve been struggling for a long time and been passed around from doctor to doctor, there’s a lot of hope right now. New agents are going to be available soon.

Talk With Others Who Understand

On MyPrurigoTeam, the social network for people with prurigo nodularis and their loved ones, members come together to ask questions, give advice, and share their stories with others who understand life with prurigo nodularis.

What have you used to treat your prurigo? What has been most effective for managing your symptoms? Share your experience in the comments below, or start a conversation by posting on your Activities page.