Monitoring of extracellular matrix metabolism and cross-linking in tissue, serum and urine of patients with chromoblastomycosis, a chronic skin fibrosis.
BACKGROUND
Chromoblastomycosis is a fungal disease leading to a granulomatous reaction associated with dermal fibrosis.


METHODS
In an attempt to elucidate the mechanisms leading to improvement in the cutaneous lesions after treatment with terbinafine, a new antifungal drug, we analysed collagen content and cross-linking before and at the end of the treatment. The turnover of extracellular matrix was monitored for 1 year by following up serum and urinary metabolites.


RESULTS
The serum levels of type III collagen and its N-terminal propeptide were correlated with the lesion size (P < 0.035) after 4 and 12 months of treatment respectively. After 4 months of treatment, urinary pyridinoline was higher (P = 0.04) in patients whose lesion size was reduced by more than 50% and serum hyaluronan was lower in patients who had lesions active for less than 5 years (P < 0.05). The treatment increased pyridinoline and pentosidine cross-links in the lesions but significantly reduced the collagen content (P = 0.05).


CONCLUSIONS
This is the first demonstration that, in addition to its fungicidal activity, terbinafine acts in vivo as an antifibrotic drug.
Ricard-Blum
S
S
Institut Pasteur de Lyon France. ricard@physio.univ-lyon1.fr
Hartmann
D J
DJ
Esterre
P
P
D000596:Amino Acids / Q000652:urine; D000935:Antifungal Agents / Q000627:therapeutic use*; D001120:Arginine / Q000031:analogs & derivatives / Q000378:metabolism; D015415:Biomarkers / Q000097:blood / Q000652:urine; D002862:Chromoblastomycosis / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D003094:Collagen / Q000097:blood / Q000737:chemistry / Q000378:metabolism; D003432:Cross-Linking Reagents; D005109:Extracellular Matrix / Q000378:metabolism*; D005355:Fibrosis; D006801:Humans; D006820:Hyaluronic Acid / Q000097:blood; D008239:Lysine / Q000031:analogs & derivatives / Q000378:metabolism; D009281:Naphthalenes / Q000627:therapeutic use*; D012867:Skin / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000077291:Terbinafine; D013997:Time Factors
D000596:Amino Acids; D000935:Antifungal Agents; D015415:Biomarkers; D003432:Cross-Linking Reagents; D009281:Naphthalenes; C015484:pyridinoline; D006820:Hyaluronic Acid; D003094:Collagen; D001120:Arginine; C062187:pentosidine; D000077291:Terbinafine; D008239:Lysine