Prurigo Nodularis: The Itch-Scratch Nodule Disease and Its New Treatments

Table of Contents

1. What Prurigo Nodularis Is
2. How Nerves and Immune Cells Keep the Itch Going
3. Who Gets It and the Conditions Linked to It
4. How It Is Diagnosed
5. What Living With It Involves
6. The Older Treatments as Studies Report Them
7. Dupilumab: The 2022 Approval and the PRIME Trials
8. Nemolizumab: The OLYMPIA Trials and the 2024 Approval
9. Side Effects Reported in the Trials and on the Labels
10. What Is Not Known
11. Key Research Papers
12. Connections
13. Featured Videos

What Prurigo Nodularis Is

A 2020 review describes prurigo nodularis as a chronic inflammatory skin disease with intensely itchy, thickened, crusty-topped nodules that favor the outer surfaces of the arms and legs and the trunk. At the time that review was written, no therapy had been approved for it by the US Food and Drug Administration, and the authors noted that many patients did not respond to the treatments then in use (Huang 2020).

In 2017, experts of the European Academy of Dermatology and Venereology agreed on a shared definition. They placed prurigo nodularis under the wider heading "chronic prurigo", which covers bumps, nodules, plaques and dimpled lesions. Chronic prurigo is defined by three things together:

• itch lasting 6 weeks or longer;
• a history or visible signs of repeated scratching;
• many itchy skin lesions, either in a few areas or spread widely, that look like whitish or pink bumps, nodules or plaques.

The same panel described the disease as the result of nerves becoming oversensitive to itch, together with an itch-scratch cycle (Pereira 2018).

Skin, whole-body, nerve and psychiatric conditions can all lead to prurigo nodularis (Zeidler 2018). A 2025 review states that once it is established, it is considered a disease in its own right, and that it can also occur in people with no other condition at all. The same review describes how scratching leads to inflammation and thickened nodules, which keeps the itch-scratch cycle going (Kwatra 2025).

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How Nerves and Immune Cells Keep the Itch Going

Itch travels mainly along very thin nerve endings that reach into the top layer of the skin. In a German study, biopsies from 53 people with prurigo nodularis were compared with skin from 20 healthy volunteers. Both the nodules and the normal-looking skin between them had fewer of these fine nerve endings than healthy skin, regardless of the person's age, the cause of their disease or how strong the itch was. The authors could not rule out that repeated scratching caused the loss, but because it was also present in skin without nodules, they raised the possibility of a hidden small-nerve disorder (Schuhknecht 2011).

Deeper in the skin, the picture is the opposite. Reviews describe raised levels of nerve signalling chemicals there, including substance P, calcitonin gene-related peptide and nerve growth factor, together with many eosinophils and mast cells, two immune cell types involved in allergy and itch. The authors describe the disease as an interaction between skin nerves and immune cells (Zeidler 2016; Zeidler 2018). A 2023 overview adds that the nodules release inflammatory signals that draw in more immune cells and make the deeper nerves grow and thicken, which keeps the itch-scratch cycle turning (Issa 2023).

Several immune messenger proteins have been linked to the disease, among them interleukin-4, interleukin-13 and interleukin-31 (Mima 2025). The two approved medicines target this system: dupilumab blocks the shared receptor for interleukin-4 and interleukin-13, and nemolizumab blocks the receptor for interleukin-31 (Yosipovitch 2023; Kwatra 2023).

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Who Gets It and the Conditions Linked to It

According to a 2025 review, prurigo nodularis is most common between the ages of 50 and 60, and some evidence suggests it is more frequent in Black populations than in White and Asian populations. Some patients have an allergic (atopic) background and also have atopic dermatitis (eczema), but the disease also occurs without it. The conditions the review lists as typically found alongside it are diabetes, obesity, thyroid disease, kidney disease, chronic liver disease, high blood pressure, HIV infection, skin infections, cancers and mental health disorders (Kwatra 2025).

The largest early study of this kind looked at 909 adults with prurigo nodularis seen in one US hospital system between 2012 and 2017:

• African American patients were 3.4 times more likely to have prurigo nodularis than white patients.
• Compared with matched patients without it, those with prurigo nodularis more often had chronic kidney disease, chronic hepatitis C, chronic obstructive pulmonary disease, congestive heart failure, depression and atopic dermatitis.
• Black patients with prurigo nodularis were 10.5 times more likely to have HIV than matched patients with atopic dermatitis, and 8 times more likely than African American patients with psoriasis.

The authors concluded that the disease is associated with HIV, chronic kidney disease and diabetes, among others. They also stated the limits: one hospital system, and data that show associations but cannot show that one condition causes another (Boozalis 2018).

A 2026 study using US health-record data matched 10,941 adults with prurigo nodularis to 10,941 people without it. Over the following five years, those with the disease had a higher recorded rate of cancer overall (hazard ratio 2.10, a measure of relative risk over time), with the highest figures for squamous cell skin cancer (hazard ratio 4.24) and basal cell skin cancer (hazard ratio 2.49). The authors called the findings preliminary and wrote that prospective studies are needed to confirm the link and to learn whether routine cancer screening helps (Lin 2026).

Mental health is part of the picture. A 2023 overview describes depression, mood disorders and substance misuse as conditions found with prurigo nodularis, alongside anxiety and poor sleep (Issa 2023).

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How It Is Diagnosed

Prurigo nodularis is diagnosed mainly by what a clinician sees and hears. A US expert panel listed three core findings: firm, raised nodules; itch lasting at least 6 weeks; and a history or signs of repeated scratching, picking or rubbing. The panel described the work-up as a complete review of body systems with attention to possible underlying diseases, plus an assessment of how severe the skin disease and the itch are (Elmariah 2021).

The British Association of Dermatologists guideline published in 2026 states that dermatologists diagnose the condition based on a history of long-lasting itching and scratching, and that the first steps include a full history and examination, including the possible causes of the itch (Millington 2026).

A 2026 set of Swiss practice recommendations covers history-taking, laboratory testing, skin biopsy and questionnaires as parts of the work-up (Mueller 2026). A skin biopsy is a small sample of skin examined under a microscope. The conditions most often found alongside the disease are listed in the section above.

The severity of the disease is usually measured in two ways in studies: a 0–10 itch score, where 10 is the worst itch imaginable, and a doctor's rating of how many nodules remain, from clear to severe. A US survey found that the number of nodules on its own did not track closely with how patients rated their disease, while the itch score did (Kwatra 2025, PN TREK).

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What Living With It Involves

A 2025 review describes intense and relentless itching, poor sleep, absence from work, anxiety and depression as common reports from people with prurigo nodularis. Scratched nodules can become inflamed and infected, which adds pain (Kwatra 2025).

In a 2022 US survey of 132 people with the disease, about 46% rated their worst itch as 7 or higher on the 0–10 scale. Those with that level of itch reported more skin pain, more nerve pain, worse sleep, worse mental health, more lost work and more health-care use than people whose itch was low. Only 23.0% of those with severe itch were satisfied with non-biologic treatments, compared with 80.8% of those whose itch score was 0 to 2 (Kwatra 2025, PN TREK).

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The Older Treatments as Studies Report Them

Before 2022, every treatment for prurigo nodularis was used "off-label", that is, it had been approved for other diseases and not for this one. The US expert panel noted that the evidence came from anecdotal reports or small clinical trials (Elmariah 2021).

A 2019 systematic review gathered 35 treatment studies with at least 5 participants each and graded their quality on the Oxford evidence scale, where a lower number means stronger evidence:

• Creams and ointments. All 5 studies of skin-applied treatments — corticosteroids, calcineurin inhibitors, calcipotriol and capsaicin — reported some benefit, at evidence level 2b or better.
• Light therapy. Six of 8 reports on ultraviolet light therapy reached evidence level 2b or better and showed good partial response rates.
• Thalidomide. Six reports described good symptom response, but only 2 reached level 2b or better.
• Cyclosporine and methotrexate. Four studies combined showed benefit, at evidence level 4.
• Nerve-targeting drugs. Pregabalin, amitriptyline, paroxetine, fluvoxamine and neurokinin-1 receptor blockers showed promising results in 5 studies at level 2b.

The authors wrote that larger randomized trials were needed (Qureshi 2019).

A 2023 systematic review of tablets and injections taken by the whole body found 88 studies, including 24 on dupilumab, 16 on thalidomide, 8 on cyclosporine and 7 on methotrexate. It concluded that dupilumab reduced itch and the appearance of lesions with the fewest side effects, that thalidomide and pregabalin were also effective but that muscle and nerve pain limited their long-term use, and that Janus kinase inhibitors may help but lack large studies (McCampbell 2023).

Guidelines now rank these options. The 2026 Swiss practice recommendations place skin-applied corticosteroids, narrowband ultraviolet B light, dupilumab and nemolizumab in their strongest category. Calcineurin inhibitor creams, zinc oxide dressings, freezing (cryotherapy), corticosteroid injections into nodules, gabapentin-type drugs, antidepressants, methotrexate, cyclosporine, mu-opioid receptor blockers, Janus kinase inhibitors and cognitive behavioral techniques sit in the middle category. The panel made no recommendation on thalidomide, lenalidomide, azathioprine, retinoids or neurokinin-1 blockers (Mueller 2026). The British guideline describes skin-applied treatment as usually the first option, followed by light therapy and tablets, with steroid injections or freezing for single nodules, and includes patient education and reversing the itch-scratch habit among the first steps (Millington 2026). For itch from other causes, see the Itching page.

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Dupilumab: The 2022 Approval and the PRIME Trials

Dupilumab is a fully human antibody given as an injection under the skin. It blocks the shared receptor part used by interleukin-4 and interleukin-13. The US Food and Drug Administration approved it for prurigo nodularis in September 2022, and Health Canada followed in July 2023; it was the first approved therapy for the disease (Alkhaleefa 2023). The Dupilumab page covers the drug across all of its uses.

The approval rested on two trials, PRIME and PRIME2. They enrolled adults with at least 20 nodules and severe itch that skin-applied treatments had not controlled — 151 people in PRIME and 160 in PRIME2. The trial gave 300 mg of dupilumab or a placebo injection every 2 weeks for 24 weeks (Yosipovitch 2023).

• PRIME, week 24: itch fell by 4 or more points on the 0–10 scale in 60.0% on dupilumab against 18.4% on placebo.
• PRIME2, week 12: the same itch drop was seen in 37.2% against 22.0%.
• Both trials met all of their planned main and key secondary goals, which included bringing the nodule count down to 5 or fewer (Yosipovitch 2023).

The US label adds further results from the same trials. At week 24 in PRIME2, the 4-point itch drop was reached by 57.7% on dupilumab against 19.5% on placebo. Clear or almost clear skin (0 to 5 nodules left) at week 24 was reached by 48.0% against 18.4% in PRIME and by 44.9% against 15.9% in PRIME2. The label gives a starting dose of 600 mg (two 300 mg injections), followed by 300 mg every 2 weeks, for adults with prurigo nodularis. It states that safety and effectiveness in children with the disease have not been established (US label, DailyMed).

Results outside trials have also been published. An Italian study followed 543 adults treated in 26 dermatology centres. The 4-point itch drop was recorded in 78.6% at week 24 and in 86.9% of those still followed at week 104, and 2.9% stopped because of side effects. People with psychiatric conditions and those who had earlier taken tricyclic antidepressants responded less well (Talamonti 2026). This study had no placebo group, so it cannot separate the drug's effect from other changes over time.

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Nemolizumab: The OLYMPIA Trials and the 2024 Approval

Nemolizumab is an antibody that blocks the receptor for interleukin-31. Its US label gives 2024 as the year of first US approval and lists the treatment of adults with prurigo nodularis as its first use. The current label also lists moderate-to-severe atopic dermatitis in people aged 12 and older (US label, DailyMed).

The first trial. In a 12-week phase 2 trial of 70 people with at least 20 nodules and severe itch, the trial gave 0.5 mg per kilogram of body weight at the start, week 4 and week 8. By week 4, the itch score had fallen by 4.5 points (53.0%) on nemolizumab against 1.7 points (20.2%) on placebo. Stomach symptoms (abdominal pain and diarrhea) and muscle and joint symptoms were reported with the drug, and the authors wrote that larger and longer trials were needed (Ständer 2020).

OLYMPIA 2. This phase 3 trial randomly assigned 274 adults, 183 to nemolizumab and 91 to placebo. The trial gave a first dose of 60 mg, then 30 mg or 60 mg depending on body weight every 4 weeks, for 16 weeks. At week 16 (Kwatra 2023):

• itch fell by 4 or more points in 56.3% against 20.9%;
• skin was clear or almost clear in 37.7% against 11.0%;
• itch had already fallen by 4 points at week 4 in 41.0% against 7.7%;
• sleep disturbance improved by 4 or more points in 51.9% against 20.9%.

OLYMPIA 1. This phase 3 trial ran at 77 centres in 10 countries and randomly assigned 286 adults, 190 to nemolizumab and 96 to placebo, for 24 weeks. At week 16, itch fell by 4 or more points in 58.4% against 16.7%, and skin was clear or almost clear in 26.3% against 7.3%. At week 24, in an analysis added after the trial's plan, the itch figures were 58.3% against 20.4%, and the skin figures 30.5% against 9.4% (Ständer 2025).

Long-term follow-up. People who finished the earlier trials could continue in an extension study. By July 2024, 290 of 508 participants (57%) had completed 100 weeks. Among those who could be assessed at week 100, 92% had a 4-point itch drop and 74% had clear or almost clear skin. These figures count only the people still in the study and do not fill in missing data (Legat 2026).

The US label gives a first dose of 60 mg (two 30 mg injections), then 30 mg every 4 weeks for adults under 90 kg and 60 mg every 4 weeks for adults of 90 kg or more (US label, DailyMed).

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Side Effects Reported in the Trials and on the Labels

Neither US label carries a boxed warning.

Dupilumab. In the pooled PRIME and PRIME2 data on the label, the side effects that were more common on the drug than on placebo were (US label, DailyMed):

• nose-and-throat infection (nasopharyngitis): 5% against 2%;
• conjunctivitis (eye-surface inflammation): 4% against 1%;
• herpes infections, including cold sores and shingles: 3% against 0%;
• dizziness: 3% against 1%;
• muscle pain: 3% against 1%;
• diarrhea: 3% against 1%.

In those trials, 0% on dupilumab and 3% on placebo stopped treatment because of side effects. Across all of the drug's uses, the label's warnings include allergic reactions, eye-surface inflammation, eosinophil-related conditions, new psoriasis, joint pain and arthritis, and parasitic worm infections (US label, DailyMed). The Dupilumab page describes these in more detail.

Nemolizumab. In OLYMPIA 1 and OLYMPIA 2 combined, through week 16, the label lists (US label, DailyMed):

• headache: 6% against 3%;
• atopic dermatitis: 4% against 0.5%;
• eczema: 4% against 2%;
• nummular (coin-shaped) eczema: 3% against 0%.

Treatment was stopped because of side effects by 4% on nemolizumab and 3% on placebo. The label's warnings cover allergic reactions, including one report of swelling around the eyes, and state that live vaccines are not to be given during treatment (US label, DailyMed). In OLYMPIA 2, headache occurred in 6.6% against 4.4% and atopic dermatitis in 5.5% against 0% (Kwatra 2023). In the long-term extension, 89% of participants had at least one adverse event of any cause during treatment, mostly mild or moderate; worsening of the prurigo itself was reported in 13% (Legat 2026). A single case report from 2025 describes erythema multiforme, a target-shaped rash, three weeks after a first dose (Mima 2025).

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What Is Not Known

• Which of the two new drugs works better. The trials read for this page compared each drug with placebo, not with each other.
• What happens over many years. The placebo-controlled trials described here lasted 16 to 24 weeks. The long-term data reach 100 to 104 weeks and come from studies without a placebo group (Talamonti 2026; Legat 2026).
• Children. The dupilumab label states that safety and effectiveness in children with prurigo nodularis have not been established, and the nemolizumab label lists the disease for adults only (US labels, DailyMed).
• Whether the nerve changes come first. Researchers could not rule out that the loss of fine nerve endings is a result of scratching rather than a cause (Schuhknecht 2011).
• The cancer link. The higher cancer rate seen in health-record data is described by its authors as preliminary, and they wrote that the benefit of routine cancer screening still needs to be evaluated (Lin 2026).
• Who responds less well. In the Italian real-world study, psychiatric conditions predicted a weaker response to dupilumab (Talamonti 2026); why this happens is not established.
• The older drugs. Most evidence for thalidomide, cyclosporine, methotrexate and the nerve-targeting drugs comes from small or low-grade studies (Qureshi 2019).

Decisions about any of these medicines belong with a clinician who knows the person's full history.

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Key Research Papers

1. Huang AH, Williams KA, Kwatra SG. Prurigo nodularis: Epidemiology and clinical features. J Am Acad Dermatol. 2020;83(6):1559-1565. PubMed PMID: 32454098
2. Pereira MP, Steinke S, Zeidler C, Forner C, Riepe C, Augustin M, et al. European academy of dermatology and venereology European prurigo project: expert consensus on the definition, classification and terminology of chronic prurigo. J Eur Acad Dermatol Venereol. 2018;32(7):1059-1065. PubMed PMID: 28857299
3. Kwatra SG, Pereira MP, Misery L, Mollanazar NK, Shah P, Wiggins S. Prurigo nodularis: disease burden, clinical features and approach to management. Br J Dermatol. 2025;193(4):642-652. PubMed PMID: 40665436
4. Schuhknecht B, Marziniak M, Wissel A, Phan NQ, Pappai D, Dangelmaier J, et al. Reduced intraepidermal nerve fibre density in lesional and nonlesional prurigo nodularis skin as a potential sign of subclinical cutaneous neuropathy. Br J Dermatol. 2011;165(1):85-91. PubMed PMID: 21410670
5. Zeidler C, Ständer S. The pathogenesis of Prurigo nodularis--'Super-Itch' in exploration. Eur J Pain. 2016;20(1):37-40. PubMed PMID: 26416433
6. Zeidler C, Yosipovitch G, Ständer S. Prurigo Nodularis and Its Management. Dermatol Clin. 2018;36(3):189-197. PubMed PMID: 29929592
7. Issa NT, Riva H, Jafferany M. INDIVIDUAL ARTICLE: Prurigo Nodularis: Current Clinicopathologic Overview and Psychodermatological Perspectives. J Drugs Dermatol. 2023;22(12):SF365502s6-SF365502s11. PubMed PMID: 38051853
8. Boozalis E, Tang O, Patel S, Semenov YR, Pereira MP, Stander S, et al. Ethnic differences and comorbidities of 909 prurigo nodularis patients. J Am Acad Dermatol. 2018;79(4):714-719.e3. PubMed PMID: 29733939
9. Lin YH, Wang YC, Chen TL, Jaun LC, Tsai CJ, Chen CC, et al. Association Between Prurigo Nodularis and Malignancy: A Real-World Multicenter Retrospective Cohort Study. J Dermatol. 2026;53(2):281-287. PubMed PMID: 41387104
10. Elmariah S, Kim B, Berger T, Chisolm S, Kwatra SG, Mollanazar N, et al. Practical approaches for diagnosis and management of prurigo nodularis: United States expert panel consensus. J Am Acad Dermatol. 2021;84(3):747-760. PubMed PMID: 32682025
11. Millington GWM, Patel PU, Chua SL, Bewley A, Sterling JC, Hughes JR, et al. British Association of Dermatologists living guideline for managing people with nodular prurigo (prurigo nodularis) 2025. Br J Dermatol. 2026;194(6):1035-1045. PubMed PMID: 41783941
12. Mueller SM, Beltraminelli H, Boehncke WH, Böhm M, Cozzio A, Häusermann P, et al. Swiss Practice Recommendations for Chronic Prurigo Including Prurigo Nodularis. Int J Dermatol. 2026;65(12):2497-2508. PubMed PMID: 42316333
13. Kwatra SG, Yang M, Martins B, Zion A, Liu J, Zahn J, et al. Prurigo Nodularis PaTient-Reported BurdEn of SicKness (PN TREK): A Cross-Sectional Survey of Patient-Reported Burden of Disease in Patients with PN from the US. Adv Ther. 2025;42(7):3455-3471. PubMed PMID: 40439955
14. Qureshi AA, Abate LE, Yosipovitch G, Friedman AJ. A systematic review of evidence-based treatments for prurigo nodularis. J Am Acad Dermatol. 2019;80(3):756-764. PubMed PMID: 30261199
15. McCampbell LE, Zaino ML, Ranpariya M, Patel T, Feldman SR. Systemic Medication for the Treatment of Prurigo Nodularis-A Systematic Review. J Cutan Med Surg. 2023;27(6):641-645. PubMed PMID: 37987710
16. Alkhaleefa A, Woo TE, Parsons L. Dupilumab for the Treatment of Prurigo Nodularis. Skin Therapy Lett. 2023;28(6):7-9. PubMed PMID: 38016088
17. Yosipovitch G, Mollanazar N, Ständer S, Kwatra SG, Kim BS, Laws E, et al. Dupilumab in patients with prurigo nodularis: two randomized, double-blind, placebo-controlled phase 3 trials. Nat Med. 2023;29(5):1180-1190. PubMed PMID: 37142763
18. Talamonti M, Mortato E, Narcisi A, Ferrucci SM, Gargiulo L, Marzano AV, et al. Dupilumab for prurigo nodularis: real-world outcomes up to 104 weeks from the Dupilumab Italian Prurigo Nodularis (DUPItaPN) study. Clin Exp Dermatol. 2026;51(9):1644-1653. PubMed PMID: 41986289
19. Ständer S, Yosipovitch G, Legat FJ, Lacour JP, Paul C, Narbutt J, et al. Trial of Nemolizumab in Moderate-to-Severe Prurigo Nodularis. N Engl J Med. 2020;382(8):706-716. PubMed PMID: 32074418
20. Kwatra SG, Yosipovitch G, Legat FJ, Reich A, Paul C, Simon D, et al. Phase 3 Trial of Nemolizumab in Patients with Prurigo Nodularis. N Engl J Med. 2023;389(17):1579-1589. PubMed PMID: 37888917
21. Ständer S, Yosipovitch G, Legat FJ, Reich A, Paul C, Simon D, et al. Efficacy and Safety of Nemolizumab in Patients With Moderate to Severe Prurigo Nodularis: The OLYMPIA 1 Randomized Clinical Phase 3 Trial. JAMA Dermatol. 2025;161(2):147-156. PubMed PMID: 39602139
22. Legat FJ, Kwatra SG, Reich A, Boulinguez S, Tsianakas A, Sauder M, et al. Nemolizumab in prurigo nodularis up to 100 weeks: OLYMPIA LTE interim analysis. J Eur Acad Dermatol Venereol. 2026;40(7):1195-1207. PubMed PMID: 41405008
23. Mima Y, Ohtsuka T. A Case of Erythema Multiforme Following the Administration of Nemolizumab. Cureus. 2025;17(2):e79070. PubMed PMID: 40104458

US prescribing information was read on DailyMed: dupilumab label and nemolizumab label.

PubMed Topic Searches

1. PubMed: prurigo nodularis pathogenesis
2. PubMed: prurigo nodularis comorbidities
3. PubMed: dupilumab and prurigo nodularis
4. PubMed: nemolizumab and prurigo nodularis
5. PubMed: chronic prurigo treatment guidelines

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Connections

• Dermatology — the skin-disease section
• Itching (Pruritus) — itch and its causes in general
• Dupilumab — the drug across all of its approved uses
• Eczema — the atopic disease many patients also have
• Chronic Urticaria — another long-lasting itchy skin disease
• Lichen Planus — another skin disease with itchy raised bumps
• Psoriasis — another long-lasting inflammatory skin disease
• Hyperphosphatemia (High Phosphate): Itching — itch in kidney disease

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