Risk of malignancy in patients with prurigo nodularis: A systematic review and meta-analysis.
Journal
Journal of the European Academy of Dermatology and Venereology : JEADV
ISSN
1468-3083
Date Issued
2025-01-16
Author(s)
Chang, Po-Yen
Abstract
Prurigo nodularis (PN) is a chronic inflammatory skin condition characterized by raised and intensely itchy nodules. The chronic itching causes repeated scratching and inflammation. Higher rates of anxiety, depression, diabetes, as well as hepatic, renal and thyroid problems, have been observed in PN patients.1, 2 Studies have investigated a potential association between PN and malignancies.3, 4 However, due to the limited number of studies, this association remains unclear. We conducted a systematic search for PN studies in PubMed, Medline, Web of Science and EMBASE from inception to January 31, 2024. The analysis was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. (registration number in PROSPERO: CRD42024505245). We included observational studies that evaluated malignancy outcomes in patients with PN and control subjects and excluded studies with overlapping cases, incomplete data, or those lacking malignancy outcomes or control groups. Data were independently screened and collected by the two authors, and a third independent researcher (T.S.W.) resolved the discrepancies. To determine the risk of malignancy in PN patients compared to control groups, pooled odds ratios (ORs) and 95% confidence intervals (CIs) were obtained by Review Manager, version 5.4.1, with a generic inverse-variance random-effects model in this meta-analysis. Out of the 2383 articles identified, 66 full-text articles were assessed for eligibility. Five studies were included in the meta-analysis, and the characteristics of the included studies were summarized in Table 1. PN was significantly associated with an increased risk of overall malignancy (OR, 2.82; 95% CI, 2.25–3.54). In the subgroup analysis stratified by cancer type, PN was associated with a significantly increased risk of lymphoma (OR, 3.44; 95% CI, 2.25–5.25), leukaemia (OR, 2.34; 95% CI, 1.55–3.52) and breast cancer (OR, 1.74; 95% CI, 1.47–2.05) compared to controls. However, a meta-analysis of studies investigating lung cancer, multiple myeloma and gastrointestinal tract malignancies showed no significant association between PN and these malignancies (Figure 1). The mechanism underlying the association between malignancy and PN remains unclear. Chronic irritation and systemic inflammation predisposing patients to tumorigenesis3 may contribute to this association. The development and progression of malignancy may be sustained by inflammatory molecules and fibroblasts in PN.9 The chronic inflammation in PN patient creates an immunosuppressed environment, predisposing to disrupted cell regulation and tumorigenesis. On the other hand, underlying malignancies that cause pruritus and excoriation might be the precursors of PN.2 Case reports showed that PN improved with cancer treatment,4 supporting this notion. Our research has limitations. Since the studies included were cross-sectional, a causal relationship between PN and malignancy could not be established. The small number of studies included, along with heterogeneity among them (Figure 1), limited the generalizability of the findings. Some types of malignancies were not included in the analysis due to sparse research, which could have skewed the results. The effects of some factors, such as age, disease duration, treatment, or comorbidities, on the cancer risks in PN were not analysed due to the unavailability of these data. The potential for publication bias may overestimate the actual magnitude of an effect. However, funnel plots and Egger's tests did not indicate the presence of publication bias. In conclusion, PN is significantly associated with an increased risk of various malignancies. Evaluation and screening for lymphoma, leukaemia and breast cancer should be considered in PN patients, especially when they meet the age-appropriate cancer screening criteria or present with associated symptoms and signs. Further research is warranted to validate our findings and develop cost-effective strategies for identifying patients at higher risk and reducing their malignancy risks. We thank Dr. Ting-Shun Wang (T.S.W.) in assistance with resolving discrepancies in data extraction between 2 authors. We thank the staff of Department of Education & Medical Research, National Taiwan University Hospital Hsin-Chu Branch for their assistance in providing careful review and insightful comments regarding study design, statistical analysis, manuscript wiring, submission and revision. This work was funded in part by grants from National Taiwan University Hospital, Hsin-Chu branch (113-HCH013, 113-HCH106, NHRI-113-H06, 114-HCH001, HR-114-H01, and 114-HCH034), the National Science and Technology Council (Ministry of Science and Technology of Taiwan) (MOST 110-2314-B-002-191, MOST 111-2314-B-002-244, NSTC 112-2314-B-002-073-MY3). The funders had no role in the study design, data collection and analysis, interpretation of findings, manuscript writing, or target journal selection. All authors have completed the ICMJE uniform disclosure form available at www.icmje.org/coi_disclosure.pdf and declare the following: H.Y.C. received speaking fees from AbbVie, Novartis Pharmaceuticals Corporation, Janssen-Cilag Pharmaceutica, Eli-Lilly, Kyowa Hakko Kirin Taiwan and Pfizer Limited and conducted clinical trials for Eli-Lilly, AbbVie and Sanofi Pharmaceuticals. P.Y.C. has no conflicts of interest to declare. This study was granted an exemption from ethical approval by the institutional review board as it involves only a systematic review and meta-analysis of published, non-identifiable data. The data that support the findings of this study are available from the corresponding author upon reasonable request.
SDGs
Type
letter