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.
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Chronic allergic contact dermatitis promotes skin cancer

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

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Figure 1

Chronic ACD promotes skin tumorigenesis.

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Chronic ACD promotes skin tumorigenesis. (A–C) Clinical case of an invas...
(A–C) Clinical case of an invasive SCC that developed in the context of ACD to nickel is shown. (A) Skin-patch test result indicated nickel allergy. (B) SCC lesion on the patient’s left lateral ankle. Note the solar lentigines on the patient’s leg that are a sign of chronic sun exposure. Also, there were no signs of vascular compromise or stasis changes (arrow marks the biopsy site). (C) Punch biopsy of the lesion demonstrated a well-differentiated, but invasive, SCC (scale bar: 100 μm), consistent with Marjolin’s ulcer. (D) Experimental design used to investigate whether chronic ACD synergizes with the surgical wound to promote tumor development. (E) Time to tumor onset and (F) average number of tumors per animal for each group. Regardless of the presence of a surgical wound, animals chronically treated with DNFB developed skin tumors with short latency (*P < 0.001 by log-rank test) and increasing tumor counts over time (*P < 0.05 starting from week 7 by Student’s t test). No skin tumors developed in the acetone-treated group, despite carcinogen exposure. Age-matched FVB female mice were used in this study; n = 6 per group.