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      The emerging role of Clostridium histolyticum collagenase in the treatment of Dupuytren disease

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          Abstract

          Dupuytren disease (DD) is a common fibroproliferative disease of unknown etiopathogenesis affecting the palmar aponeurosis, causing reduced hand function and resulting in fixed flexion contractures of the digits. Current gold standard treatment for the management of DD is surgical excision involving removal of the affected palmar fascial tissue. However, there are potential complications associated with surgery as it is costly and a positive surgical outcome is often short-lived because the disease tends to recur. Therefore, there is growing interest in nonsurgical, outpatient-based treatments that could be quicker, cheaper, reduce morbidity, show a decreased rate of recurrence, and give DD patients an improved quality of life when compared with traditional surgical management. Of the available nonsurgical options, injectable Clostridium histolyticum collagenase (CHC) has received recent clinical interest. In this article, a brief overview of DD surgical and nonsurgical treatments utilized is given, followed by a detailed examination of the nine papers published to date on the use of CHC in DD (and similar fibrotic disorders). These papers have investigated safe and efficacious doses for the injection of CHC to treat palpable DD cords in adult patients and have shown significant short- to mid-term results for correction to near-full digital extension (≤5° extension) following CHC injection of DD cords. CHC has been shown to target the collagen-based DD cords while sparing surrounding neurovasculature, with a complication profile that appears comparable to that of the surgical methods currently utilized. In conclusion, clostridial collagenase is a novel nonsurgical treatment option of considerable potential in the management of DD when administered by specialist hand surgeons with detailed knowledge of the disease and the relevant anatomy. Nonetheless, there is a need for further data on long-term results, complications, and rate of recurrence with the use of this emerging treatment option.

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          Most cited references 39

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          Free radicals and Dupuytren's contracture.

          The concentration of substrate expressed as hypoxanthine capable of reacting with xanthine oxidase to release superoxide free radicals (O2-) was measured in control and Dupuytren's contracture palmar fascia. In Dupuytren's contracture palmar fascia the concentration of hypoxanthine was six times that of control and was greatest in "nodular" areas. Xanthine oxidase activity was also detected in Dupuytren's contracture palmar fascia. These results suggest a greater potential for hypoxanthine-xanthine oxidase generated oxygen free radical formation in Dupuytren's contracture than in control palmar fascia. Production of free radicals may be an important factor in the pathogenesis of Dupuytren's contracture. The benefit of allopurinol in the management of Dupuytren's contracture and other fibrotic conditions may thus be explained, as allopurinol binds to xanthine oxidase and prevents release of free radicals.
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            Cigarette smoking and Dupuytren's contracture of the hand.

            Microvascular occlusion has been implicated as a possible causative factor of Dupuytren's contracture. Cigarette smoking is one of the most significant factors in the development of peripheral vasculopathy. The relationship between smoking and Dupuytren's contracture of the hand is explored in this article. One hundred thirty-two consecutive patients who had a partial fasciectomy for treatment of Dupuytren's contracture from 1980 to 1985, were analyzed retrospectively. There were 111 males and 21 females. Ninety (68.2%) of 132 patients smoked cigarettes compared with 110 (37.2%) of 296 randomized hospitalized control patients (p less than 0.00001). Eighty (72.1%) of 111 men smoked cigarettes compared with 65 (44.2%) of 147 male control patients (p = 0.000015). Cigarette smoking is linked statistically to Dupuytren's disease and may be involved in its pathogenesis by producing microvascular occlusion and subsequent fibrosis and contracture or by some other mechanism.
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              Radiotherapy for prevention of disease progression in early-stage Dupuytren's contracture: initial and long-term results.

              Radiotherapy (RT) was given to prevent disease progression in early-stage Dupuytren's contracture. Initial response, long-term outcome, and treatment toxicity were evaluated.
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                Author and article information

                Journal
                Ther Clin Risk Manag
                Therapeutics and Clinical Risk Management
                Therapeutics and Clinical Risk Management
                Dove Medical Press
                1176-6336
                1178-203X
                2010
                2010
                4 November 2010
                : 6
                : 557-572
                Affiliations
                [1 ] Plastic and Reconstructive Surgery Research, School of Translational Medicine, University of Manchester, Manchester Interdisciplinary Biocentre, Manchester, UK
                [2 ] Department of Plastic and Reconstructive Surgery, Manchester Academic Health Science Centre, University Hospital of South Manchester National Health Service Foundation Trust, Wythenshawe Hospital, Manchester, UK
                Author notes
                Correspondence: Ardeshir Bayat, Plastic and Reconstructive Surgery Research, Epithelial Sciences, University of Manchester, Manchester Interdisciplinary Biocentre, 131 Princess St, Manchester M1 7DN, UK, Tel +44 161 306 5177, Email ardeshir.bayat@ 123456manchester.ac.uk
                Article
                tcrm-6-557
                10.2147/TCRM.S8591
                2988615
                21127696
                © 2010 Thomas and Bayat, publisher and licensee Dove Medical Press Ltd.

                This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.

                Categories
                Review

                Medicine

                fibrosis, enzymatic injection, nonsurgical treatment, dupuytren contracture

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