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itch: the invisible symptom of prurigo nodularis

Prurigo nodularis (PN) is a rare, understudied skin disease with an estimated prevalence of 72 per 100,000 people in the US population and 148.3 per 100,000 people in the Medicare population, many of whom have experienced a significant delay in diagnosis.1-4 Persistent severe itching, or pruritis, is one of the primary symptoms of PN and causes substantial discomfort to patients.5  

What is PN?

PN is a chronic, debilitating, and distinct neuroimmune skin disease characterized by chronic pruritus and multiple localized or generalized pruriginous lesions.4,6,7 Most patients with PN develop numerous hyperkeratotic nodules accompanied by burning, stinging, pain, and severe and intractable itching.7-9

What is the pathophysiology of PN?

Immune cells and overactivation of the skin’s immune response are central contributors to the disease pathophysiology, inflammation, and severe itching experienced by patients with PN.10 The activation of certain cytokine receptors, such as IL-31RA, on sensory nerves can release neuropeptides and induce the neurogenic inflammation that causes itching.7,10

Why is talking about itching important?

The presence of persistent and severe pruritus in patients with PN is debilitating and considered a substantial health burden. Itching contributes to the severity and duration of the disability associated with the disease and causes greater morbidity than other chronic diseases, such as diabetes and anxiety.5

What is the impact of itching on patients with PN?

The itching associated with PN significantly affects patients’ well-being and impairs their quality of life. Most patients with PN suffer from sleep disturbances and consistent social isolation due to the intense and persistent itching they experience.9,11-14  Itch severity in patients with PN is greater than in other skin diseases characterized by itching.9,15,16

What are the challenges of PN?

Despite significant impacts to the quality of life for patients with PN, an internationally accepted clinical itch classification does not currently exist. A classification system would help diagnose patients with PN and other chronic pruritic diseases and help optimize the medical care needed to treat this challenging condition.17


  1. Ständer S, Augustin M, Berger T, et al. Prevalence of prurigo nodularis in the United States of America: a retrospective database analysis. JAAD Int. 2020;2:28-30. doi:10.1016/j.jdin.2020.10.009

  2. Whang KA, Kang S, Kwatra SG. Inpatient burden of prurigo nodularis in the United States. Medicines. 2019;6(3):88. doi:10.3390/medicines6030088

  3. Huang AH, Canner JK, Khanna R, Kang S, Kwatra SG. Real-world prevalence of prurigo nodularis and burden of associated diseases. J Invest Dermatol. 2020;140(2):480-483.e4. doi:10.1016/j.jid.2019.07.697

  4. Huang AH, Williams KA, Kwatra SG. Prurigo nodularis: epidemiology and clinical features. J Am Acad Dermatol. 2020;83(6):1559-1565. doi:10.1016/j.jaad.2020.04.183

  5. Janmohamed SR, Gwillim EC, Yousaf M, Patel KR,  Silverberg JI. The impact of prurigo nodularis on quality of life: a systematic review and meta-analysis. Arch Dermatol Res. 2021;313(8), 669-677. doi:10.1007/s00403-020-02148-0

  6. Pereira MP, Steinke S, Zeidler C, 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. doi:10.1111/jdv.14570

  7. Ständer S, Pereira MP, Berger T, et al. IFSI-guideline on chronic prurigo including prurigo nodularis. Itch. 2020;5(4):e42. doi:10.1097/itx.0000000000000042

  8. Kowalski EH, Kneiber D, Valdebran M, Patel U, Amber KT. Treatment-resistant prurigo nodularis: challenges and solutions. Clin Cosmet Investig Dermatol. 2019;12:163-172. doi:10.2147/CCID.S188070

  9. Aggarwal P, Choi J, Sutaria N, et al. Clinical characteristics and disease burden in prurigo nodularis. Clin Exp Dermatol. 2021;46(7):1277-1284. doi:10.1111/ced.14722

  10. Williams KA, Huang AH, Belzberg M, Kwatra SG. Prurigo nodularis: pathogenesis and management. J Am Acad Dermatol. 2020;83(6):1567-1575. doi:10.1016/j.jaad.2020.04.182

  11. Konda D, Chandrashekar L, Rajappa M, Kattimani S, Thappa DM, Ananthanarayanan PH. Serotonin and interleukin-6: association with pruritus severity, sleep quality and depression severity in prurigo nodularis. Asian J Psychiatr. 2015;17:24-28. doi:10.1016/j.ajp.2015.07.010

  12. Ständer S, Ketz M, Kossack N, et al. Epidemiology of prurigo nodularis compared with psoriasis in Germany: a claims database analysis. Acta Derm Venereol. 2020;100(18):adv00309. doi:10.2340/00015555-3655

  13. Gwillim EC, Nattkemper L, Yosipovitch G. Impact of itch on sleep disturbance in patients with prurigo nodularis. Acta Derm Venereol. 2021;101(3):adv00424. doi:10.2340/00015555-3778

  14. Whang KA, Le TK, Khanna R, et al. Health-related quality of life and economic burden of prurigo nodularis. J Am Acad Dermatol. 2021;S0190-9622(21)01028-8. doi:10.1016/j.jaad.2021.05.036

  15. Kwatra SG. Breaking the itch–scratch cycle in prurigo nodularis. N Engl J Med. 2020;382(8):757-758. doi:10.1056/NEJMe191673

  16. Steinke S, Zeidler C, Riepe C, et al. Humanistic burden of chronic pruritus in patients with inflammatory dermatoses: results of the European Academy of Dermatology and Venereology Network on Assessment of Severity and Burden of Pruritus (PruNet) cross-sectional trial. J Am Acad Dermatol. 2018;79(3):457-463.e5. doi:10.1016/j.jaad.2018.04.044

  17. Ständer, S., Weisshaar, E., Mettang, T., et al. Clinical classification of itch: a position paper of the International Forum for the Study of Itch. Acta Derm Venereol. 2007;87(4):291-294.



*Expert author(s), speaker(s) or contributor(s) where indicated are paid Galderma consultants.

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