Monitoring of extracellular matrix metabolism and cross‐linking in tissue, serum and urine of patients with chromoblastomycosis, a chronic skin fibrosis

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Abstract
Chromoblastomycosis is a fungal disease leading to a granulomatous reaction associated with dermal fibrosis. 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. 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). This is the first demonstration that, in addition to its fungicidal activity, terbinafine acts in vivo as an antifibrotic drug.