Prurigo Nodularis Linked to Increased Risk of Malignancy, Especially Skin Cancers

Prurigo nodularis is associated with a notable elevation in patients’ risk of malignancy, new findings suggest, particularly with cutaneous cancers.1

Sheng-Hsiang Ma, MD, of Taipei Veterans General Hospital, led a team of other investigators in authoring this study evaluating links between risk of various forms of cancer and prurigo nodularis. The skin disease has previously been associated with different systemic conditions such as atopic dermatitis, chronic kidney disease, chronic hepatitis C infection, and psychiatric disorders.

Additionally, Ma and colleagues highlighted prior data suggesting neural sensitization and prurigo nodularis’s increased nerve growth factor expression serving as potential influences on tumor growth among different types of patients.2

“This study aims to elucidate the association between [prurigo nodularis] and the risk of malignancy, with the goal of informing clinical practice and guiding future research direction,” Ma and coauthors wrote.1

Design and Findings

Ma et al's study involved a retrospective cohort design, with the team drawing on data from the TriNetX database. TriNetX is a global federated research network designed to gather de-identified electronic health records from participating healthcare systems, including both community hospital and academic center data. Within this platform, there is longitudinal, continuously updated clinical data from more than 130 million patients, the majority of whom are US-based.

The TriNetX analytics interface is designed to allow access to detailed information on patients' different diagnoses, demographic data, medication exposures, laboratory findings, and any previous procedures. Data extraction and analysis occurred in February 2025, with Ma and colleagues using a subset of TriNetX that includes 68 healthcare organizations known as the US Collaborative Network.

In their analysis, the team's study population was made up of adults diagnosed with prurigo nodularis (n = 10,941). These individuals were matched in a 1:1 ratio to subjects who did not have prurigo nodularis (n = 10,941). Ma and coauthors' matching criteria included comorbid conditions, demographic characteristics, and medication utilization. Their study's main endpoint was the hazard ratio for the development of malignancy taking place in the period between 3 months - 5 years following the study's index date. Hazard ratios and corresponding 95% confidence intervals were estimated via Cox proportional hazards regression models.

Overall patients with prurigo nodularis, compared with matched controls, were shown by Ma et al to be at a significantly higher risk of malignancy development, with a hazard ratio of 2.10 (95% CI, 1.81–2.43).1 The investigators found elevated risks were especially pronounced for specific types of cancer, including basal cell carcinoma (HR 2.49; 95% CI, 1.68–3.69), cutaneous squamous cell carcinoma (HR 4.24; 95% CI, 2.69–6.69), hematopoietic malignancies (HR 1.97; 95% CI, 1.26–3.06), cancers impacting the respiratory system (HR 1.86; 95% CI, 1.23–2.82), gastrointestinal cancers (HR 1.87; 95% CI, 1.24–2.81), and female genital cancers (HR 2.77; 95% CI, 1.29–5.95).

Ma and colleauges' findings of malignancy risk suggest prurigo nodularis is linked with a markedly raised malignancy risk. In specific, the team highlighted the strongest associations being with cutaneous cancers. While the analysis's retrospective and observational design was acknowledged by Ma and coauthors to limit causal inference, the robust sampling, large sample size, and use of real-world data strengthen the validity of their data.

Ma et al's observations highlight the value of raising clinical awareness and surveillance. Additionally, the investigative team's data support the necessity for future prospective studies to validate these links, as well as to clarify potential biological mechanisms and determine whether routine cancer screening may be helpful for individuals with skin condition.

“Large-scale, prospective studies are warranted to confirm these associations, elucidate underlying mechanisms, and assess the potential benefits of risk-adapted malignancy surveillance in this high-risk population,” the team wrote.1

References

1. YY Lin, YC Wang, TL Chen, et al. Association Between Prurigo Nodularis and Malignancy: A Real-World Multicenter Retrospective Cohort Study. The Journal of Dermatology (2025): 1–7, https://doi.org/10.1111/1346-8138.70112.

2. Ferraguti G, Terracina S, Fiore M, et al. Nerve Growth Factor and the Role of Inflammation in Tumor Development. Curr Issues Mol Biol. 2024 Jan 23;46(2):965-989. doi: 10.3390/cimb46020062. PMID: 38392180; PMCID: PMC10888178.