Prurigo nodularis (PN) is a chronic pruritic inflammatory skin disease characterized by hyperkeratotic papules and nodules symmetrically distributed on the back and extensor surfaces of the extremities, accompanied by severe pruritus. PN has a serious impact on quality of life.[1–3] PN is a complex and difficult-to-treat condition. There is a lack of unified understanding of its diagnosis and treatment specifications, and the means approved for treating PN are limited; thus, clinicians mostly use empirical therapies.
There are still discrepancies in the definition, classification, and terminology of PN in relevant global guidelines or expert consensuses.[3–5] In the United States and Japan, the term “PN” is used to describe this condition, whereas in Europe, it is described as chronic prurigo. This guideline adopts the definition of PN. PN can be an independent disease or a manifestation of other diseases, such as atopic dermatitis (AD). PN is coded L28.1 in the International Classification of Diseases (ICD)-10 and EC91.0 in the ICD-11. Following the methodological requirements for developing evidence-based clinical practice guidelines and based on the best available evidence and expert opinions, the working group developed the Guidelines for the Diagnosis and Treatment of Prurigo Nodularis to provide guidance and reference for clinicians (Supplementary File, http://links.lww.com/CM9/C544). This guideline has been registered at the International Practice Guideline Registry Platform (http://www.guidelines-registry.org; No. PREPARE-2022CN784).
Questions, Recommendations, and Evidence Grade
The guidelines summarize 13 key clinical questions related to the status, diagnosis, treatment, and management of PN based on the results of literature analysis and expert opinions. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to classify the quality of evidence into four levels and the strength of recommendation into two levels. Recommendations were finally formulated in combination with expert opinions and experience.[6]
Clinical question 1: What are the epidemiological profile and disease burden of PN?
Recommendations:
▪ The incidence of PN increases with age, and intractable pruritus seriously affects the quality of life of patients. [GRADE: 1B] [Agreement: 95%; Indetermination: 5%]
▪ PN has a severe direct and indirect disease burden. [GRADE: 1B] [Agreement: 100%]
Clinical question 2: What is the primary pathogenesis of PN?
Recommendations:
▪ The specific pathogenesis of PN remains unclear. The role of immune and neurological factors in its development has attracted increasing attention, and these factors have become potential therapeutic targets. [GRADE: 2B] [Agreement: 100%]
Clinical question 3: What diagnostic criteria are recommended for PN?
Recommendations:
▪ The diagnosis of PN requires a complete medical history, thorough physical examination, and laboratory tests. [GRADE: 1A] [Agreement: 100%]
▪ Attention should be given to the following four points: the presence of multiple localized or generalized nodular lesions; persistent pruritus for more than 6 weeks; a history of or clinical evidence of long-term scratching behavior; and the exclusion of other clinically similar diseases. [GRADE: 1B] [Agreement: 100%]
▪ Accurate and early diagnosis is vital for optimizing disease management and scar prevention. [GRADE: GPS] [Agreement: 95%; Disagreement: 5%]
Clinical question 4: Which diseases should PN be differentiated from?
Recommendations:
▪ PN needs to be differentiated from many other diseases, with pruritus as the main manifestation. [GRADE: 2B] [Agreement: 100%]
▪ The differential diagnosis requires a combination of medical history, lesion features, and, when necessary, skin biopsy or dermoscopy. [GRADE: 2C] [Agreement: 100%]
Clinical question 5: How to grade the severity of the disease and evaluate treatment efficacy?
Recommendations:
▪ The severity of the disease should be evaluated by combining the number of nodules, the severity of pruritus, the condition of the skin lesions, and the impact of the disease on quality of life. [GRADE: 1B] [Agreement: 100%]
▪ The severity of pruritus should be rated by the Worst Itch Numeric Rating Scale, skin lesions should be rated by the Investigator Global Assessment for Prurigo Nodularis Stage and Prurigo Activity Score, and skin-related quality of life should be rated by the Dermatology Life Quality Index. [GRADE: 2B] [Agreement: 100%]
Clinical question 6: What are the treatment principles of PN?
Recommendations:
▪ Long-term or complete control of the disease can be achieved by controlling pruritus, restoring skin lesions, and fully considering the treatment of comorbidities. The treatment regimen should be selected after thoroughly weighing the pros and cons regarding drug safety and improvement in quality of life. [GRADE: GPS] [Agreement: 100%]
Clinical question 7: How to provide health education for patients with PN, and what precautions should be taken in life?
Recommendations:
▪ The management of primary diseases and comorbidities (including mental and psychological problems) should be strengthened. [GRADE: GPS] [Agreement: 100%]
▪ Health education on wearing, bathing, and skin care should be strengthened for patients. [GRADE: GPS] [Agreement: 95%; Indetermination: 5%]
Clinical question 8: How to treat PN with or without AD?
Recommendations:
▪ For patients with concomitant AD, treatment regimens that can address both diseases simultaneously should be given priority. [GRADE: GPS] [Agreement: 95%; Indetermination: 5%]
▪ For patients with nonatopic diseases related to PN, the interaction of different treatment regimens should be fully evaluated, the control of underlying diseases should be strengthened, and multidisciplinary consultation should be coordinated when necessary. [GRADE: GPS] [Agreement: 95%; Indetermination: 5%]
Clinical question 9: How to apply glucocorticoids?
Recommendations:
▪ For patients with mild PN, topical glucocorticoids are recommended. [GRADE: 2C] [Agreement: 100%]
▪ For patients with fewer than 20 hypertrophic skin lesions, intralesional injection is recommended. [GRADE: 2C] [Agreement: 100%]
▪ Long-term systemic use of glucocorticoids is not recommended. [GRADE: 1B] [Agreement: 100%]
Clinical question 10: How to apply topical calcineurin inhibitors and other topical agents?
Recommendations:
▪ Topical calcineurin inhibitors can be used in patients with PN, especially those requiring long-term maintenance therapy or intolerant to topical glucocorticoids. [GRADE: 2C] [Agreement: 95%; Indetermination: 5%]
Clinical question 11: How to apply biological agents?
Recommendations:
▪ Interleukin-4 receptor blockers, such as dupilumab, are recommended as the first-line systemic treatment for patients with PN that cannot be controlled by local therapy. [GRADE: 1A] [Agreement: 95%; Indetermination: 5%]
Clinical question 12: How to apply Janus kinase inhibitors?
Recommendations:
▪ Observational studies have suggested that Janus kinase inhibitors can improve pruritus and disease severity in the treatment of PN; however, high-quality research evidence is still lacking. [GRADE: D] [Agreement: 95%; Indetermination: 5%]
Clinical question 13: How to apply antihistamines?
Recommendations:
▪ The clinical efficacy of antihistamines for PN has not been fully validated and may require high doses or combinations with other treatments. The limited use of antihistamines is recommended in the early stage of PN. [GRADE: 2C] [Agreement: 95%; Indetermination: 5%]
In summary, PN is a chronic pruritic disease that seriously affects the quality of life of patients. It can occur alone or be associated with other underlying medical conditions, including skin diseases, psychological disorders, and systemic disorders. Intractable pruritus and the chronic recurrent course of the disease seriously affect the lives of patients, and the treatment of PN has long been a clinical challenge. With a deeper understanding of the etiology and mechanism of PN, several randomized controlled trials using targeted therapies have been conducted, and dupilumab has emerged as an indication drug by the Food and Drug Administration. Undoubtedly, there is still a need to develop more targeted and individualized treatment regimens for PN to meet the diverse treatment needs of patients.
Funding
This work was partly supported by a grant from the National Key Research and Development Programme of China (No. 2023YFC2508200).
Supplementary Material
Footnotes
How to cite this article: Zhang L, Diao QC, Dou X, Fang H, Geng SM, Guo H, Chen YL, Ji C, Li CX, Li LF, Li J, Li JY, Li W, Li ZM, Liang YS, Qiao JJ, Song ZQ, Sun Q, Tao J, Wang F, Xie ZQ, Xu JH, Xu SL, Yan HW, Yao X, Zhang JZ, Zhang LT, Zhu G, Hao F, Gao XH. Guidelines for the diagnosis and treatment of prurigo nodularis. Chin Med J 2025;138:2859–2861. doi: 10.1097/CM9.0000000000003732
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