Chronic allergic contact dermatitis promotes skin cancer

J Clin Invest. 2014 Nov;124(11):5037-41. doi: 10.1172/JCI77843. Epub 2014 Oct 8.

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.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinogenesis / immunology
  • Carcinoma, Squamous Cell / diagnosis*
  • Carcinoma, Squamous Cell / immunology
  • Carcinoma, Squamous Cell / surgery
  • Chronic Disease
  • Dermatitis, Allergic Contact / complications*
  • Dermatitis, Allergic Contact / pathology
  • Female
  • Humans
  • Internal Fixators / adverse effects
  • Mice, Inbred C57BL
  • Middle Aged
  • Nickel / immunology
  • Skin Neoplasms / diagnosis*
  • Skin Neoplasms / immunology
  • Skin Neoplasms / surgery

Substances

  • Nickel