Br J Dermatol. 2004 Sep;151(3):627-35. Related Articles, Links


Oxidative stress is implicated in the pathogenesis of lichen sclerosus.

Sander CS, Ali I, Dean D, Thiele JJ, Wojnarowska F.

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

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.

PMID: 15377350 [PubMed - indexed for MEDLINE]

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