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Br J Dermatol. 2004 Sep;151(3):627-35.

Oxidative stress is implicated in the pathogenesis of lichen sclerosus.

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1
Dermatology Department, The Churchill Hospital, Old Road, Oxford OX3 7LJ, UK.

Abstract

BACKGROUND:

Lichen sclerosus (LS) is a chronic inflammatory skin disease of unknown aetiology which can be associated with secondary malignancies. Recent evidence supports an autoimmune basis for this disorder, as demonstrated by autoantibodies to extracellular matrix protein 1 (ECM-1). The pathophysiological mechanisms leading to autoimmunity and carcinogenesis are poorly understood.

OBJECTIVES:

We hypothesized that oxidative stress, which has been demonstrated to be involved in the pathogenesis of several autoimmune and malignant disorders, contributes to these processes in LS.

METHODS:

Skin biopsies from 16 patients with untreated, histologically confirmed vulval LS were examined immunohistochemically using antibodies against the lipid peroxidation products malondialdehyde and 4-hydroxynonenale and against the oxidative DNA damage marker 8-hydroxy-2'-deoxyguanosine. Protein carbonyls as markers of protein oxidation were visualized using the dinitrophenylhydrazone method. Expression of antioxidant enzymes was investigated. Normal vulval tissue from 16 subjects served as control.

RESULTS:

In vulval LS tissue a significant increase of lipid peroxidation products was found particularly within the basal cell layers of the epidermis, thus colocalizing with ECM-1. Oxidative DNA damage was detected throughout LS biopsies. Intriguingly, protein oxidation was significantly increased within the dermis of LS lesions, indicating oxidative protein damage in the areas of sclerosis and inflammation. The enzymatic antioxidant defence in LS was found to be significantly disturbed.

CONCLUSIONS:

This is the first study to demonstrate oxidative damage to lipids, DNA and proteins in LS, revealing a novel pathophysiological mechanism which may contribute to sclerosis, autoimmunity and carcinogenesis. Therapeutic strategies using antioxidants might be a useful new approach in the treatment of LS and could also help to prevent secondary malignancies.

[Indexed for MEDLINE]

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