Collagenase Injection as Nonsurgical Treatment of Dupuytren's Disease: 8-Year Follow-Up

Department of Surgery, Stanford University Hospitals and Clinics, Palo Alto, CA 94304, USA.
The Journal of hand surgery (Impact Factor: 1.67). 04/2010; 35(4):534-9, 539.e1. DOI: 10.1016/j.jhsa.2010.01.003
Source: PubMed


Collagenase has been investigated in phase II and phase III clinical trials for the treatment of Dupuytren's disease. The purpose of this study is to report 8-year follow-up results in a subset of patients who had collagenase injection for the treatment of Dupuytren's contracture.
Twenty-three patients who participated in the phase II clinical trial of injectable collagenase were contacted by letter and phone. Eight patients were enrolled, completed a Dupuytren's disease questionnaire, and had independent examination of joint motion by a single examiner.
Eight patients completed the 8-year follow-up study: 6 had been treated for isolated metacarpophalangeal (MCP) joint contracture, and 2 had been treated for isolated proximal interphalangeal (PIP) joint contracture. Average preinjection contracture was 57 degrees in the MCP group. Average contracture was 9 degrees at 1 week, 11 degrees at 1 year, and 23 degrees at 8-year follow-up. Four of 6 patients experienced recurrence, and 2 of 6 had no evidence of disease recurrence at 8-year follow-up. Average preinjection contracture was 45 degrees in the PIP group. Average contracture was 8 degrees at 1 weeks, 15 degrees at 1 year, and 60 degrees at 8-year follow-up. Both patients experienced recurrence at 8-year follow-up. No patients had had further intervention on the treated finger in either the MCP or the PIP group. Patients subjectively rated the overall clinical success at 60%, and 88% of patients stated that they would pursue further injection for the treatment of their recurrent or progressive Dupuytren's disease.
Enzymatic fasciotomy is safe and efficacious, with initial response to injection resulting in reduction of joint contracture to within 0 degrees -5 degrees of normal in 72 out of 80 patients. Initial evaluation of long-term recurrence rates suggests disease recurrence or progression in 4 out of 6 patients with MCP contractures and 2 patients with PIP contractures; however, recurrence was generally less severe than the initial contracture in the MCP group. In addition, patient satisfaction was high.

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    • "For example, Dupuytren's cords are now being treated with direct injection of collagenase [15]. Collagenases will breakdown collagen within the cords and this allows the surgeon to break the cord by hyperextending the fingers [15]. Recurrence of cord contracture [16] and extensive deep tissue scarring [17] are well-known complications of this management approach. "
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    ABSTRACT: Generally speaking, the excessive expression of myofibroblasts is associated with excessive collagen production. One exception is seen in patients and animal models of Ehlers-Danlos syndrome type IV in which the COL3A1 gene mutation results in reduced collagen III but with concurrent increased myofibroblast expression. This paradox has not been examined with the use of external drugs/modalities to prevent hypertrophic scars. In this paper, we injected the rabbit ear wound model of hypertrophic scarring with two doses of a protein called nAG, which is known to reduce collagen expression and to suppress hypertrophic scarring in that animal model. The higher nAG dose was associated with significantly less collagen III expression and concurrent higher degree of myofibroblast expression. We concluded that collagen III content of the extracellular matrix may have a direct or an indirect effect on myofibroblast differentiation. However, further research is required to investigate the pathogenesis of this paradoxical phenomenon.
    02/2015; 2015:1-6. DOI:10.1155/2015/958695
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    • "However, several limitations must be noted. The first limitation is related to the progress of treatment with CCH, because even though 8-year progress studies [24] are available, the number of cases involved does not allow us to draw conclusions regarding the long-term progress of these patients after fasciectomy. Rates of early recurrence and other types of disorders (such as skin retractions) should also be assessed. "
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    ABSTRACT: Our purpose was to analyze and compare the use of direct health resources and costs generated in the treatment of Dupuytren's contracture using two different techniques: subtotal fasciectomy and infiltration with Collagenase Clostridium Histolyticum (CCH) in regular clinical practice at the Orthopedic and Traumatology Surgery (OTS) Department at the Hospital de Denia (Spain). Observational, retrospective study based on data from the computerized clinical histories of two groups of patients- those treated surgically using a one or two digit subtotal fasciectomy technique (FSC) and those treated with CCH infiltration, monitored in regular clinical practice from February, 2009 to May, 2012. Demographic (age, sex), clinical (number of digits affected and which ones) and use of resources (hospitalizations, medical visits, tests and drugs) data were collected. Resource use and associated costs, according to the hospital's accounting department, were compared based on the type of treatment from Spain's National Health Service. 91 patients (48 (52.8%) in the FSC group) were identified. The average age and number of digits affected was 65.9 (9.2) years and 1.33 (0.48) digits affected in the FSC group, and 65.1 (9.7) years and 1.16 (0.4) digits in the CCH group.Overall, the costs of treating Dupuytren's disease with subtotal FSC amount to [euro sign]1,814 for major ambulatory surgery and [euro sign]1,961 with hospital stay including admission, surgical intervention ([euro sign]904), examinations, dressings and physiotherapy. As to collagenase infiltration, costs amount to [euro sign]952 (including minor surgery admission, vial with product, office examination and dressings). Finally, comparing total costs for treatments, a savings of [euro sign]388 is estimated in favor of CCH treatment in the best-case scenario (patient under MAS system with no need for physiotherapy) and [euro sign]1,008 in the worst-case scenario (patient admitted to hospital needing subsequent physiotherapy), implying a savings of 29% and 51%, respectively. This study demonstrates that treating patients with DC by injection with CCH at the OTS department of the Hospital de Denia generates a total savings of 29% and 51% ([euro sign]388 and [euro sign]1008) compared with fasciectomy at the time of treatment. Long term evolution of CCH treatment is uncertain and the recurrence rate unknown.
    BMC Musculoskeletal Disorders 10/2013; 14(1):293. DOI:10.1186/1471-2474-14-293 · 1.72 Impact Factor
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    • "In recent years, the collagenolytic activity of these enzymes has been exploited in clinical and therapeutic applications, particularly to treat the Dupuytrens' disease [2] and various types of destructive fibrosis such as liver cirrhosis [3]. Collagenases are also used as hydrolyzing agents to obtain collagen peptides with important biological activities, among which antioxidant agents [4], functional foods to relieve memory deficits associated with aging [5] and ingredients for dietary materials and parentally-fed products [6]. "
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    ABSTRACT: Aqueous two-phase systems (ATPS) of PEG/phosphate were used to recover collagenase from Penicillium aurantiogriseum from fermented broth. Experiments were carried out according to a 24-full factorial design using the PEG molar mass (MPEG), PEG concentration (CPEG), phosphate concentration (CPHOS) and pH as the independent variables, and the purification factor (PF), partition coefficient (K) and activity yield (Y) as the responses. All the responses increased in the top phase with increasing CPEG and CPHOS and decreasing MPEG, but the maximum value of PF (5.23) was obtained at the lowest pH (6.0), that of Y (61.68%) and K (1.52) at the highest one (8.0). The electrophoretic profile revealed that some protein contaminants were removed by the ATPS, and the extracted collagenase exhibited optimum activity at pH 8.0 and 45 °C. The proposed ATPS appears to be a promising alternative to conventional first-step operations for direct recovery of collagenase from fermented broths, yielding a concentrate enzyme solution able to effectively hydrolyze collagen.
    Biochemical Engineering Journal 06/2013; 75:64–71. DOI:10.1016/j.bej.2013.03.012 · 2.47 Impact Factor
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