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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.

SUBMITTER: Demehri S

PROVIDER: S-EPMC4347218 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Chronic allergic contact dermatitis promotes skin cancer.

Demehri Shadmehr S Cunningham Trevor J TJ Hurst Eva A EA Schaffer Andras A Sheinbein David M DM Yokoyama Wayne M WM

The Journal of clinical investigation 20141008 11

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 hyper ...[more]

PMID: 25295539

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Project description:Genes involved in the inflammatory response resulting in allergic contact dermatitis (ACD) are only partly known. In this study, we introduce the use of high density oligonucleotide arrays for gene expression profiling in human skin during the elicitation of ACD. Skin biopsies from normal and nickel-exposed skin were obtained from 7 nickel-allergic patients and 5 non-allergic controls at four different time points during elicitation of eczema: 0h, 7h, 48h and 96h. Each gene expression profile was analysed by hybridization to high density oligonucletide arrays. Cluster analysis of 74 genes found to be differentially expressed in the patients over time revealed that the patient samples may be categorised into two groups: An early time point group (0h and 7h) and a late time point group (48h and 96h). Compared to the early time points, late time point skin samples were characterised by the up-regulation of inflammatory molecules including genes involved in the class I antigen presenting pathway and genes involved in lymphocyte adhesion and motility ; Correspondence analysis including both patients and controls revealed three distinct groups: i) the control group, ii) the early time point patient group (0h and 7h) and iii) the late time point patient group (48h and 96h). Experiment Overall Design: For the microarray study, 7 nickel-allergic patients and 5 non-allergic controls were recruited. All subjects were female. The skin covering the upper nates was exposed to nickel delivered during a patch test. Skin biopsies were taken to generate a time-series. Skin was exposed to nickel for 0h, 7h, 48h and 96h. Experiment Overall Design: All nickel allergic patients reacted with visible eczama at the 48h and 96h time-points. No eczema was vissible at the 0h or 7h time-points. Control subjects did not show visible eczema at any time-point. Experiment Overall Design: RNA was extracted from the skin biopsies and 34 biopsies yielded RNA of sufficient quantity and quality for micro-array analysis.

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Chronic allergic contact dermatitis promotes skin cancer.

Publications

Chronic allergic contact dermatitis promotes skin cancer.

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