Current role of the collagenase Clostridium histolyticum in Dupuytren's disease treatment.

BACKGROUND: Collagenase Clostridium histolyticum (CCH) is a recent treatment for Dupuytren disease, which is a fibroproliferative disorder that leads to progressive, persistent digital flexion contracture that interferes with basic daily activities. While CCH has changed the treatment of this hand disorder, numerous concerns have to be analyzed. AIMS: Our purpose is to assess the current status of this medical treatment. METHODS: Literary review based on a manual search on PubMed, Web of Science, and Google Academic. RESULTS: Pharmacoeconomic analyses support the use of CCH, but long-term studies showing that it should be favored over conventional surgery or other treatments are lacking. Treatment decisions, therefore, must be guided by current data, which include a 5-year recurrence rate of 47%. Complications following CCH treatment are also a controversial topic, as rates of over 90% have been reported, although most of the complications are mild and self-limiting. A definition and classification of CCH-related complications is sorely needed. If we exclude adverse effects that could be considered inherent to the mechanisms of action of CCH, then the complication rate would be similar to rates reported for other techniques. Although CCH is becoming an increasingly popular treatment for Dupuytren disease, the potential applications of this modality, are much higher than currently believed, for more disorders characterized by excessive fibrosis. CONCLUSION: Currently, the administration of this treatment is promising although long-term studies are necessary to see the real role that this drug can play in both Dupuytren's disease and other fibrotic disorders.

Determination of the cytotoxic effect of Clostridium histolyticum culture supernatant on HeLa cells in the presence of protease inhibitors.

Clostridium histolyticum culture supernatant contains numerous enzymes, which exert a cytotoxic effect on host cells. This includes lethal toxin, clostripain and high-potassium-sensitive toxin. Since the number of C. histolyticum infections increased during the last several years, it seems worthwhile to evaluate whether protease inhibitors, used for the treatment of many diseases, could influence toxicity, and thus, pathogenicity of C. histolyticum. In this study we evaluated in vitro the influence of four common protease inhibitors: aprotinin, phenylmethylsulphonyl fluoride (PMSF), l-1-chloro-3-[4-tosylamido]-7-amino-2-heptanone-HCl (TLCK) and chymostatin on the toxicity of C. histolyticum supernatant towards human epithelial HeLa cells. We show that aprotinin has no effect, while PMSF, TLCK and chymostatin potentiate the cytotoxic activity of C. histolyticum, probably by hindering natural defence mechanisms of cells. In addition, PMSF and TLCK block clostripain enzymatic activity, while chymostatin leaves it intact. Elevated cytotoxicity of the supernatant is not related to the quantity of high-potassium-sensitive toxin, as was reported previously, since desalted supernatant still exerted its strong toxic effect. Our results show that addition of protease inhibitors for treating diseases complicated by concurrent C. histolyticum infection must require special attention.