Welcome to the CCO Site

Thank you for your interest in CCO content. As a guest, please complete the following information fields. These data help ensure our continued delivery of impactful education. 

Become a member (or login)? Member benefits include accreditation certificates, downloadable slides, and decision support tools.


Current Treatment Landscape and Promising New Therapies for Patients With Prurigo Nodularis

Benjamin Ungar, MD

Assistant Professor
Department of Dermatology
Icahn School of Medicine at Mount Sinai
New York, New York

Benjamin Ungar, MD: consultant/advisor/speaker: Arcutis; researcher: Incyte, Pfizer, Rapt Therapeutics.

View ClinicalThoughts from this Author

Released: September 16, 2022

Key Takeaways:

  • Prurigo nodularis (PN) is a rare skin condition but it has a significant impact on a patient’s quality of life
  • Current treatment involves addressing both immunologic and neurologic components to address the itch-scratch cycle present in PN
  • There are several emerging treatment strategies that may provide significant benefits to patients with PN who are not responding to currently available medications

Approximately 87,000 new cases of prurigo nodularis (PN) occur annually in the US, making PN an uncommon, under-diagnosed, and often under-treated inflammatory skin condition. Patients with PN pick and scratch at hyperpigmented skin nodules that can be localized on the trunk or extremities or can be widespread. The itching of PN is very uncomfortable—especially if the trigger is ongoing—and the PN nodules themselves are also symptomatic. PN can be cosmetically unappealing and can look so dramatic that patients avoid exposure to others. The impact on patient quality of life is considerable.

Clinical Characteristics
PN is a clinical diagnosis. PN nodules vary in appearance and are typically round, but they can be dome-shaped or flat, often with excoriations. Depending on the skin type, the nodules are darker or red in color when compared with the surrounding skin. The butterfly sign is an area of sparing on the upper mid-back—in the shape of a butterfly where patients are unable to reach and scratch—that can be a clue that the PN itch-scratch cycle is occurring. Many patients also have excoriations or scratches at the top of the nodule dome caused by picking and scratching. Lesion biopsies are not typically done because they are unlikely to provide additional information beyond the clinical examination of the PN lesions.

In order to diagnose a possible underlying condition in a new patient with PN, I order routine bloodwork as part of the initial work-up. It should include a complete blood count and a complete metabolic panel to check kidney and liver functions. If kidney or liver disease is identified, patients can be referred to the appropriate specialists for management of the underlying condition.

When I see a patient with PN, I consider 2 aspects of this skin condition. First, what has triggered the itching, scratching, or picking? Atopic dermatitis, kidney disease, liver disease, and sometimes peripheral neurologic issues can cause generalized itching that initiates the second aspect of the PN process, the itch-scratch cycle. Even though PN usually develops as its own entity, the itch-scratch cycle continues in a way that is very difficult to break and can be difficult to treat with available treatment options.


Immunologic Treatment Options
PN can be localized to 1 or more extremities or to the trunk, but patients can also have nodules all over their body and this makes treatment of PN challenging.

The use of topical steroids is a good starting point to alleviate itching caused by an inflammatory process. Topical steroids also help ease symptoms in the nodules themselves. When the number of nodules is limited (ie, <10), injection of intralesional steroids into the nodules can relieve symptoms, reduce the inflammatory process that contributes to nodule development, and help break the itch-scratch cycle.

When these 2 interventions are insufficient (either because the topical steroids do not lessen symptoms or when injection of numerous nodules is not feasible because of very widespread involvement), long-term phototherapy should be considered. Phototherapy with UVB light is often effective regardless of the specific itch etiologies so I would have this conversation with my patient immediately. The challenge of phototherapy is that the patient must consistently go in for treatment 2-3 times/week for a period of weeks to months. The effects of phototherapy require several weeks to manifest, but it can be very effective and is a good first-line treatment for patients with more widespread disease.

When phototherapy is ineffective or not an option, I then think about oral, systemic immune-suppressing medications (ie, cyclosporine, methotrexate, or mycophenolate mofetil) to reduce the inflammatory process contributing to the itching and the itch-scratch cycle. The side effects and risks of some of these treatment options include fatigue, nausea, low blood counts, changes in renal and hepatic functions, blurry vision, weight gain, and others which make people reluctant to use them.

Systemic steroids (ie, prednisone) can be used to treat PN with the goal of interrupting the itch-scratch cycle. However, prednisone is not a good long-term treatment option and should be used with caution. When tapering prednisone monotherapy, there is a risk for rebound itching and rebound disease that can make PN more difficult to treat in the future.

Neurologic Treatment Options
Itch is probably a primary cause for the development of PN, but peripheral nerve symptoms can also contribute. Therefore, targeting the neurologic components that may contribute to PN onset and perpetuation could be beneficial. Studies have shown that gabapentin, pregabalin, and certain tricyclic antidepressants can reduce or resolve itch. Additionally, aprepitant may be used to treat PN based on recent studies. The role of opioid receptors in itch is also recognized, and treatments that target specific opioid receptors offer another potential treatment approach for PN.

Emerging Therapies
The good news is that very promising treatments that appear to be very effective and not associated with the same degree of side effects may soon be available. Dupilumab, an interleukin (IL)-4 receptor alpha antagonist that blocks IL-4 and IL-13 signaling, is currently FDA approved for atopic dermatitis and other allergy-related diseases like asthma and is in a phase III trial for PN. Dupilumab has been shown to be safe, and studies have found it can be very effective in treating PN in many patients.

Once a patient starts dupilumab, the itching and other symptoms lessen, the itch-scratch cycle is reduced, and over time, the clearance of nodules occurs. Currently, a patient with PN and concomitant atopic dermatitis would be a candidate for dupilumab.

Another promising treatment, nemolizumab, is an antibody targeting IL-31, the itch cytokine pathway. Nemolizumab is in studies for several conditions, including atopic dermatitis, but the promising results of the phase III OLYMPIA 2 trial for PN showed it was safe and efficacious.

Therefore, potentially we will soon have 2 widely available, biologic options that that are not associated with the side effects of the broad-acting immune-suppressing medications currently in use.

Since biologics not currently an option, finding an effective alternative treatment strategy can be challenging. I am reluctant to give broad-acting immunosuppressants if there are other alternatives that may be effective for an underlying issue. For example, certain treatments may be more effective in people who have kidney or liver disease, and using more specific, targeted approaches that are very patient dependent may be the best option.

Your Thoughts
What are your thoughts on the place of biologics in the treatment armamentarium for PN? Please answer the polling question and share your thoughts in the comments box below.

Provided by Partners for Advancing Clinical Education (PACE) and Clinical Care Options, LLC (CCO) in collaboration with Practicing Clinicians Exchange (PCE).

Contact Clinical Care Options

For customer support please email: customersupport@cealliance.com

Mailing Address
Clinical Care Options, LLC
12001 Sunrise Valley Drive
Suite 300
Reston, VA 20191

Produced in collaboration with
Supported by educational grants from
Boehringer Ingelheim Pharmaceuticals, Inc.

Leaving the CCO site

You are now leaving the CCO site. The new destination site may have different terms of use and privacy policy.


Cookie Settings