Review Explores Potential Treatments for Prurigo Nodularis

A recent review found that new methods of treatment for prurigo nodularis had promising results, including approaches that target interleukin 31 and its receptor.

A review published in Dermatology and Therapy highlighted the various treatments that are demonstrating promise in treating prurigo nodularis (PN), particularly in targeting interleukin-31 (IL-31) and its receptor IL-31RA to diminish skin lesions.

PN, also known as chronic nodular prurigo, is an inflammatory skin disease that causes chronic itching, pruritic nodular lesions, repeated scratching, and lichenification. Skin conditions have been demonstrated as having a negative effect on patient well-being, which is exacerbated in chronic skin diseases. Different methods of treating PN are currently being investigated to test their efficacy and improve quality of life in patients with the disease.

PN is thought to be a rare condition, with approximately 170,000 adults in the United States diagnosed with the disease. However, experts believe that PN may be underreported due to a lack of education and awareness of the disease. PN is most often diagnosed in people 50 years and older. It is also associated with medical conditions including kidney disease, liver disease, chronic obstructive pulmonary disease, diabetes, heart failure, high blood pressure, and mental health problems.

PN causes itchy skin lesions in those it affects, with 51.2% of patients reporting severe or very severe pruritus in 1 study. The lesions can also be heterogeneous, ranging in size, appearance, and location. A total of 71% of patients with PN said in a study from 2020 that they had an intractable itch all or most of the time with moderate to severe intensity. The same study found that 53.1% of patients reported a negative impact on their daily life and 42.5% reported some form of sleep disturbance. Moderate to severe pain was also found to be common in PN, with 80% of patients reporting moderate to severe pain or discomfort.

Experts have hypothesized that the pathogenesis of PN would involve neuronal sensitization, inflammation, and pruritus. IL-31 has been found at 50-fold higher levels in PN lesions compared with skin from healthy individuals, which has led to researchers believing that it could be involved in sensory nerve fibers, fibroblasts, epidermal keratinocytes, and immune cells crosstalk with eosinophils.

The diagnosis of PN is determined through evaluation and assessed by number and appearance of nodules. The prurigo activity score and the investigator global assessment are 2 formal tools that can help clinicians assess disease severity and monitor the effectiveness of treatment.

Treatments for PN have been varied with unpredictable benefits, the review authors wrote. Corticosteroids and calcineurin inhibitors have not been found to be effective against moderate to severe disease, despite providing relief for some symptoms. Immunosuppressants, gabapentinoids, thalidomide, and antidepressants can be used as systemic therapies but do not target the pathophysiological mechanisms of the disease. Ultraviolet phototherapy could be helpful in older patients who are on various medication. However, there is no established standard treatment.

Promising data have emerged when targeting IL-31 and its receptor IL-31RA with nemolizumab, which is a monoclonal antibody used against IL-31RA that is under investigation in treating PN. A randomized, double-blinded phase 2 study was conducted with patients who had 20 or more nodules with a mean pruritus score of at least 7 out of 10.

The peak pruritus numerical rating scale (PP NRS) was reduced from 8.4 to 3.9 (53.0% reduction) at the 4-week mark of the study in the group treated with nemolizumab. The placebo group had a smaller reduction in their PP NRS, from 8.4 at baseline to 6.7 (20.2% reduction) at the same time period. Improvements in sleep quality, investigator global assessment, and Dermatology Life Quality Index, as well as a reduction in number of lesions, were also observed. The FDA has granted approval of the drug with breakthrough therapy status for patients with PN.

Dupilumab, which is an anti–IL-4RA monoclonal antibody, is also being tested for treatment of PN due to its effectiveness in patients with atopic dermatitis. Case reports have demonstrated that dupilumab treatment has reduced pruritus and number of lesions after 3 months. Opioid antagonists and cannabinoids have shown promise as well, as both are associated with a reduction in itching intensity in patients with PN.

The authors concluded that new hope for treatments for patients with PN exists as new targeted treatments are being discovered to deal with itching intensity and reduction in lesions. They highlighted that blocking the IL-31 pathway via IL-31RA has demonstrated a significant effect for patients with PN.


Bewley A, Homey B, Pink A. Prurigo nodularis: a review of IL-31RA blockade and other potential treatments. Dermatol Ther. 2022;12:2039-2048. doi:10.1007/s13555-022-00782-2

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