Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Pancreatic Cancer (Jul 2025)
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Chronic allergic contact dermatitis promotes skin cancer
Shadmehr Demehri, … , David M. Sheinbein, Wayne M. Yokoyama
Shadmehr Demehri, … , David M. Sheinbein, Wayne M. Yokoyama
Published October 8, 2014
Citation Information: J Clin Invest. 2014;124(11):5037-5041. https://doi.org/10.1172/JCI77843.
View: Text | PDF
Brief Report Oncology

Chronic allergic contact dermatitis promotes skin cancer

  • Text
  • PDF
Abstract

Allergic contact dermatitis (ACD) is well recognized as an adverse event associated with implantable medical devices that contain allergenic materials like nickel; however, other cutaneous consequences of chronic exposure to allergens in implanted devices are not well understood. Here, we present a clinical case of Marjolin’s ulcer, an invasive squamous cell carcinoma (SCC) that developed in response to chronic ACD caused by an orthopedic implant. We used a standard murine model of contact hypersensitivity to determine whether chronic ACD promotes skin carcinogenesis. Chronic application of 1-fluoro-2,4-dinitrobenzene (DNFB) to carcinogen-treated skin led to the development of papillomas and aggressive SCC. DNFB-driven chronic ACD was marked by type 2 inflammation, which mediated skin carcinogenesis, as mice unable to mount an inflammatory response were less likely to develop skin tumors. Importantly, we found similar tumor-promoting inflammation surrounding the SCC in our patient. Our findings demonstrate that chronic ACD caused by constant exposure to an allergen can promote tumorigenesis at skin sites with preexisting cancer-initiated cells. Moreover, our results suggest that patients with implantable devices placed in close proximity to the skin should be monitored for ACD and highlight the importance of patch testing prior to the placement of such devices.

Authors

Shadmehr Demehri, Trevor J. Cunningham, Eva A. Hurst, Andras Schaffer, David M. Sheinbein, Wayne M. Yokoyama

×

Figure 2

Chronic ACD manifests protumorigenic factors and mediates the tumor-promoting effects of DNFB.

Options: View larger image (or click on image) Download as PowerPoint
Chronic ACD manifests protumorigenic factors and mediates the tumor-prom...
(A) Representative H&E-stained skin images from mice treated with DNFB for 14 weeks and their acetone-treated controls (scale bars: 100 μm). Note the extent of epidermal hyperplasia and dermal inflammation in the DNFB-treated skin. (B) Quantitative real-time PCR analysis of cytokine expression by major Th cell subtypes performed on skin from mice treated with DNFB for 14 weeks compared with cytokine expression in acetone-treated controls (n = 4 in each group; *P < 0.05 by Student’s t test). (C) Il6 expression in skin treated with DNFB for 14 weeks was compared with that in skin of acetone-treated controls (n = 4 in each group; *P < 0.05 by Student’s t test). (D) Average number of mast cells in 6 random high-power microscopic fields (HPF) of skin from animals treated chronically with DNFB was compared with that of acetone-treated mice (*P < 0.05 by Student’s t test). Representative images of toluidine blue–stained skin sections show increased number, size, and granularity of mast cells in DNFB-treated skin (scale bar: 50 μm). (E and F) Tumor outcome of Rag-KO, Ragγc-KO, and WT animals in response to DNFB plus surgical wounding (following the protocol described in Figure 1D). (E) Shown are the time to tumor onset (*P < 0.01 by log-rank test) and (F) average number of tumors per animal for each of the 4 groups (*P < 0.05 starting from week 10 by Student’s t test). Age-matched C57BL/6 female mice were used in this study; n > 7 per group.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts