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Available online at

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Literature review

Complications after treating Dupuytren’s disease. A systematic literature review Complications apre`s traitement de la maladie de Dupuytren. Revue syste´matique de la litte´rature C. Krefter a, M. Marks b, S. Hensler b, D.B. Herren a,*, M. Calcagni c a

Department of Hand Surgery, Schulthess Klinik, Lengghalde 2, 8008 Zurich, Switzerland Department of Teaching, Research and Development, Schulthess Klinik, Lengghalde 2, 8008 Zurich, Switzerland c Division of Plastic Surgery and Hand Surgery, University Hospital Zurich, Raemistrasse 100, 8091 Zurich, Switzerland b

A R T I C L E I N F O

A B S T R A C T

Article history: Received 19 April 2017 Received in revised form 28 June 2017 Accepted 3 July 2017 Available online xxx

The objective of this study was to review the incidence of complications associated with different treatment options for patients with Dupuytren’s disease. In a systematic literature review, the PubMed, EMBASE, Cochrane and Scopus databases were searched for clinical studies reporting complications after collagenase treatment, percutaneous needle fasciotomy (PNF), fasciectomy and dermofasciectomy. The incidence of complications was extracted from each study and stratified by procedure. From a total of 2251 references, 113 studies were analyzed and included with complication incidences varying from 0% to 100%. The highest number of nerve and vessel lesions were reported after fasciectomy, whereas the highest rate of edema was after collagenase injection. Accidental skin tears were mostly associated with collagenase and PNF treatment. Pooled complication incidences were 17.4% (95% CI: 11.7–23.1) for fasciectomy, 78.0% (95% CI: 59.6–96.4) for collagenase treatment, 18.9% (95% CI: 5.5–43.3) for PNF and 11.6% (95% CI: 0.0–23.2) for dermofasciectomy. Due to inconsistencies in reporting complications as well as the lack of a standardized definition, the literature does not provide evidence in favor of a specific procedure for Dupuytren’s disease. A standardized definition of complications is required to improve the comparability of published results.

C 2017 SFCM. Published by Elsevier Masson SAS. All rights reserved.

Keywords: Dupuytren’s disease Complication Collagenase Percutaneous needle fasciotomy Fasciectomy Dermofasciectomy

R E´ S U M E´

Mots cle´s : Maladie de Dupuytren Complication Collage´nase Fasciotomie a` l’aiguille percutane´e Fasciectomie Dermofasciectomie

L’objectif de cette e´tude e´tait d’e´valuer l’incidence des complications associe´es aux diffe´rentes options de traitement pour les patients atteints de la maladie de Dupuytren. Dans le cadre d’une revue syste´matique de la litte´rature, les bases de donne´es PubMed, EMBASE, Cochrane et Scopus ont e´te´ consulte´es a` la recherche d’e´tudes cliniques rapportant les complications suite au traitement par la collage´nase, la fasciotomie percutane´e a` l’aiguille (FPA), la fasciectomie et la dermofasciectomie. L’incidence des complications pour chaque e´tude a e´te´ examine´e et e´value´e stratifie´e par intervention. Sur un total de 2251 re´fe´rences, 113 e´tudes ont e´te´ analyse´es et ont inclus des incidences de complications variant de 0 a` 100 %. La majorite´ des le´sions nerveuses et vasculaires ont e´te´ signale´es apre`s fasciectomie, alors que l’œde`me e´tait plus fre´quent apre`s traitement par injection de collage´nase. Les ruptures cutane´es accidentelles e´taient principalement associe´es a` la collage´nase et a` la FPA. Les incidences combine´es de complication e´taient de 17,4 % (IC 95 % : 11,7 a` 23,1) pour la fasciectomie, 78,0 % (IC 95 % : 59,6 a` 96,4) pour le traitement a` la collage´nase, 18,9 % (IC 95 % : 5,5 a` 43,3) pour la FPA et 11,6 % (IC a` 95 % : 0,0–23,2) pour la dermofasciectomie. En raison d’incohe´rences dans le rapport des complications et de l’absence de de´finitions standardise´es, la litte´rature ne fournit pas une conclusion de´finitive plaidant pour une

* Corresponding author. E-mail address: [email protected] (D.B. Herren). http://dx.doi.org/10.1016/j.hansur.2017.07.002 C 2017 SFCM. Published by Elsevier Masson SAS. All rights reserved. 2468-1229/

Please cite this article in press as: Krefter C, et al. Complications after treating Dupuytren’s disease. A systematic literature review. Hand Surg Rehab (2017), http://dx.doi.org/10.1016/j.hansur.2017.07.002

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intervention spe´cifique pour la maladie de Dupuytren. Afin d’ame´liorer la comparabilite´ des re´sultats, une de´finition standardise´e des complications est requise.

C 2017 SFCM. Publie ´ par Elsevier Masson SAS. Tous droits re´serve´s.

Numerous studies describe conservative and surgical treatment options for Dupuytren’s disease. Non-surgical treatment of Dupuytren’s disease ranges from physical therapy, splinting, injecting steroids and enzymes to radiation therapy [1–3]. The new method of injecting collagenase in affected cords has certainly modified treatment options [4,5]. Invasive treatment options vary from percutaneous needle fasciotomy (PNF) to total fasciectomy with skin grafts and flaps and in severe cases, finger amputation. Complications after minimally invasive procedures such as PNF and collagenase injection include edema, hematoma, skin tears and complex regional pain syndrome (CRPS) [6,7]. After surgical treatment, hematoma, delayed wound healing, altered feeling in the fingers, nerve, tendon and vessel lesions, infection and CRPS have been reported [8–13]. The occurrence of complications influences clinical and patientreported outcomes. Furthermore, these events can prolong treatment and increase costs. Knowledge of the risk of developing different complications makes it easier for both the physician and patient to choose the most appropriate procedure. Nevertheless, it is still unclear which complications are generally associated with the various available procedures and how frequently these events occur. Therefore, the primary objective of this study was to analyze the literature for complications and their frequency in the different treatment options for patients with Dupuytren’s disease.

subjected to a similar systematic selection process as the one for the originally included set of publications. Data for the following variables were extracted by one author using a predefined form and included: number of study patients included; gender; age; follow-up time; type of surgical or nonsurgical treatment and recurrence rates. Furthermore, we extracted all events that were defined as ‘‘adverse event’’ or ‘‘complication’’. The Cochrane quality appraisal [16,17] was used to assess the risk of bias of the individual studies chosen. Six categories (i.e. sequence generation, allocation concealment, blinding of participants, incomplete outcome data, selective outcome reporting and other sources of bias) were classified as low, unclear or high risk of bias. The level of evidence was also reported. Complications were categorized into four main procedure groups: collagenase; fasciectomy (including total and partial fasciectomy, vy- and z-plasties, and open palm); dermofasciectomy (including skin grafts) and PNF (including mini-open fasciotomy). An additional category included various procedures such as radiation therapy, corticosteroid injection, intraoperative topical treatment with 5-fluorouracil and amputations, which were not analyzed in further detail. The complication rate for each study was calculated by dividing the number of overall complications and specific complications by the total number of patients in the study. The average complication rate of all studies, stratified according to the procedure category, was calculated using means and 95% confidence intervals (CIs) over all corresponding studies.

2. Material and methods

3. Results

This systematic literature review was performed in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement for developing study protocols and reporting systematic reviews [14,15]. The online literature search was performed on the PubMed, EMBASE, Cochrane and Scopus databases, starting in January 1995 and last updated on April 18, 2014 by an experienced librarian. Key terms included ‘‘Dupuytren contracture’’, ‘‘Dupuytren disease’’, ‘‘surger’’, ‘‘non surgic’’, ‘‘operativ’’, ‘‘non operativ’’, ‘‘fasciectom’’, ‘‘dermofasciectom’’, ‘‘aponeurotom’’, ‘‘aponeurectom’’, ‘‘collagen’’, ‘‘clostrid’’, ‘‘histolyticum’’, ‘‘xiaflex’’, ‘‘therapeutics’’, ‘‘treatment outcome’’, ‘‘surgical procedures’’, ‘‘operative procedures’’, ‘‘collagenases’’ and ‘‘injections’’, and were tailored for every database. Articles were included if they had information on the occurrence of Dupuytren’s disease and treatment, were clinical trials with 10 or more patients, and were published between 01/01/1995 and 04/18/2014. Only articles written in English, German or French were considered. References were excluded when they did not report on human subjects, when the sample size was less than 10, when a specific treatment for Dupuytren’s disease was not the focus of the study or when the full text version was not published. Three independent reviewers screened the titles and abstracts of all identified publications. The full text versions of the selected articles were retrieved and analyzed again independently by two of the authors. Consensus on which full version articles would be included was reached by discussion. Lastly, the reference list of the included articles was screened for additional suitable papers and

A total of 2251 articles published between January 1995 and April 2014 were identified using the above-defined literature search strategy. After exclusion of duplicates, checking of associated reference lists, and the two-phase review process, data were extracted from 113 studies (Fig. 1, Appendix). Of 113 reviewed articles, 20,020 patients were included and divided into a total of 183 procedures groups that received either surgical or non-surgical treatment (Table 1). Overall, most studies described the outcome after fasciectomy (n = 71) followed by collagenase treatment (n = 26). The mean follow-up period was 3 years. In the four main procedure groups, complications were reported in 54 of 124 (44%) procedure groups. The reported complication rate in single studies varied from 0% to 100% (Fig. 2), with mean complication rates of 11.6% and 78% for dermofasciectomy and collagenase treatment, respectively (Table 2). The rates of nerve lesion after fasciectomy and dermofasciectomy were 3.4% and 5.6%, respectively; the rates of nerve damage after these surgical treatments were 4.1% and 5.6%. Edema was reported as a complication after fasciectomy, collagenase injection and PNF with rates of 10.4%, 62% and 5.9%, respectively. The rate of recurrence varied from 0% to 90%. The lowest rate of recurrence was reported after dermofasciectomy, and higher rates were found after PNF, collagenase injection, radiation therapy and partial fasciectomy treatments (Fig. 2). Most of the 113 studies had an unclear to high risk of bias for the study design and reporting factors (Table 3). For one third of the studies (n = 38) the level of evidence was categorized as either III and IV.

1. Introduction

Please cite this article in press as: Krefter C, et al. Complications after treating Dupuytren’s disease. A systematic literature review. Hand Surg Rehab (2017), http://dx.doi.org/10.1016/j.hansur.2017.07.002

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Fig. 1. Study diagram.

Table 1 Characteristics of the articles included in this systematic review. n Published articles Procedure group Fasciectomy (partial, total) Collagenase injection Percutaneous needle fasciotomy Dermofasciectomy Othera Patients (based on 158 procedure groups) Fasciectomy (partial, total) Collagenase injection Percutaneous needle fasciotomy Dermofasciectomy Othera Follow up [years] (based on 99 procedure groups) Age [years] (based on 132 procedure groups) Gender, male (based on 133 procedure groups)

113 183 71 26 16 11 59 20,020 4467 3858 1477 402 9816

Mean (SD) %

127 (319)

3.0 (3.0) 62.6 (4.7) 12,839

76.4

SD: standard deviation. a Including radiation therapy, corticosteroid injections, amputation.

4. Discussion This literature review about complications and their frequency after different treatments Dupuytren’s disease shows that more severe complications occur after fasciectomy, while many nonsevere complications occur after minimally invasive procedures. Most nerve and vessel lesions were reported after fasciectomy, and edema was seen most often after collagenase injection. Treatment recommendations for Dupuytren’s disease are based mostly on expert opinion. In 2013, a group of 39 experts initiated a Delphi consensus to develop the first European guidelines for treating Dupuytren’s disease [18]. Studies that were included to develop these guidelines also indicated a lack of consensus on the treatment options for this condition including lack of a standardized definition of

complications and recurrences. In the literature, recurrence rates vary from 0% to 90% [19–22]. Most of the studies define recurrence as a reappearance of any Dupuytren’s tissue in an area that has been operated previously. The lowest rates of recurrence are observed after dermofasciectomy and skin grafting [23–26]. The more recent systematic review by Rodrigues et al. [13] compared various surgical treatment options and confirmed it was impossible to conclude one treatment was superior to another. Furthermore, the long-term outcomes and complications for various procedures need to be investigated further [27]. Edema, hematoma and skin tears are specific post-procedure complications mostly reported for patients undergoing collagenase injection and PNF [28–30]; the complication rate of up to 78% is considered very high. Yet it is questionable whether a skin tear, which can heal without further intervention, should be regarded as a complication. Therefore, the high complication rate of collagenase treatment must be interpreted carefully, bearing in mind that most of these events are not serious. Edema and hematoma commonly occur after any surgical procedure, which may be the reason why these events were not highlighted as complications in most reviewed studies. It is possible that the occurrence of edema is very similar in surgical treatments and collagenase injection. Serious complications, such as nerve and vessel lesions, occur more often during the later stages of the disease when more extensive surgery is needed [8,28,31–33]. The randomized controlled trial by Scherman et al. [27] compared 1-year results of PNF and collagenase injection. There was no significant difference between the rate of skin tears after the two treatments, which is consistent with our findings. Our study has some limitations. Only a few studies reported the number of complications, e.g. 6 of 11 dermofasciectomy studies. The same staging method was rarely used, so there is no distinction between different outcomes or treatment indications according to the severity of the disease. In general, the 113 selected articles have

Please cite this article in press as: Krefter C, et al. Complications after treating Dupuytren’s disease. A systematic literature review. Hand Surg Rehab (2017), http://dx.doi.org/10.1016/j.hansur.2017.07.002

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Fig. 2. Complication and recurrence rates for each procedure.

Table 2 Complications and complication rates for each procedure. Type of procedure (na)

Complication

Reported in study groups (n)

Complication rate (%)

95% CI

Fasciectomy (n = 71)

Overall Nerve lesion Vessel lesion Skin lesion Joint stiffness Wound dehiscence Hematoma Infection Edema CRPS Flap necrosis Overall Skin lesion Tendon lesion Hematoma Edema Lymphadenopathy Overall Nerve lesion Vessel lesion Skin lesion Infection Pain Edema Lymphadenopathy CRPS Overall Nerve lesion Vessel lesion Skin lesion Wound dehiscence Hematoma Infection CRPS

28 12 5 1 1 7 5 15 2 8 1 13 9 3 6 10 9 7 4 1 4 1 2 3 1 4 6 1 1 1 1 2 1 2

17.4 3.4 4.1 1.4 10.0 4.5 2.8 7.0 10.4 10.2 10.0 78.0 23.6 4.0 24.6 62.0 15.2 18.9 1.9 0.5 19.9 1.1 5.2 5.9 0.0 1.3 11.6 5.6 5.6 7.7 10.3 0.5 0.0 4.1

11.7–23.1 2.4–4.4 0.5–7.6

Collagenase (n = 26)

Percutaneous needle fasciotomy (n = 16)

Dermofasciectomy (n = 11)

0.1–9.1 0.5–5.1 3.8–10.2 111.3–132.2 0.3–20.2 59.6–96.4 12.8–34.5 6.0–14.1 2.0–47.1 39.9–84.1 6.7–23.7 5.5–43.3 0.5–4.2 12.3–52.1 5.2–5.2 17.4–29.1 0.8–3.5 0.0–23.2

58.5–68.5 15.0–23.1

C: confidence interval; CRPS: complex regional pain syndrome. a Number of intervention groups.

Please cite this article in press as: Krefter C, et al. Complications after treating Dupuytren’s disease. A systematic literature review. Hand Surg Rehab (2017), http://dx.doi.org/10.1016/j.hansur.2017.07.002

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Sequence generation Allocation concealment Blinding of participants Incomplete outcome data Selective outcome reporting Other sources of bias

Low

Unclear risk

High risk

35 35 16 49 42 13

22 22 8 25 36 77

56 56 89 39 35 23

a low level of evidence. Another issue is the lack of a standardized definition of complications. Some authors, for example, specified a skin tear after collagenase injection as a complication, while others only reported serious events such as tendon lesions. Additionally, some authors consider recurrence as a complication. This may lead to an overestimation of the complication rates, especially in the collagenase treatment group. Therefore, a standard definition of a complication after each procedure for Dupuytren’s disease needs to be developed; this has already been achieved for orthopedic complications in general [34] and more specifically for rotator cuff tears [35]. An international consensus regarding these definitions would facilitate the interpretation and comparison of study results. Disclosure of interest The authors declare that they have no competing interest. Acknowledgements The authors thank Dr. sc. nat. M. Gosteli of the University of Zurich for searching the literature, Dr. M. Wilhelmi of the Schulthess Klinik for editing the manuscript and PD Dr. phil. L. Audige´ of the Schulthess Klinik for translating the abstract.

Appendix A Final selection of 113 studies from the defined literature search spanning January 1995 to April 2014. [1] Abe Y, Rokkaku T, Ofuchi S, Tokunaga S, Takahashi K, Moriya H. Surgery for Dupuytren’s disease in Japanese patients and a new preoperative classification. J Hand Surg Br 2004;29:235–9. [2] Adamietz B, Keilholz L, Grunert J, Sauer R. [Radiotherapy of early stage Dupuytren disease. Long-term results after a median follow-up period of 10 years]. Strahlenther Onkol 2001;177:604–10. [3] Akhavani MA, McKinnell T, Kang NV. Quilting of full thickness grafts in the hand. J Plast Reconstr Aesthet Surg 2010;63:1534–7. [4] Ali SN, McMurtrie A, Rayatt S, Roberts JO. Ulnar-based skin flap for Dupuytren’s fasciectomy. Scand J Plast Reconstr Surg Hand Surg 2006;40:307–10. [5] Anwar MU, Al Ghazal SK, Boome RS. Results of surgical treatment of Dupuytren’s disease in women: a review of 109 consecutive patients. J Hand Surg Am 2007;32:1423–8. [6] Anwar MU, Al Ghazal SK, Boome RS. The lateral digital flap for Dupuytren’s fasciectomy at the proximal interphalangeal joint– a study of 84 consecutive patients. J Hand Surg Eur Vol 2009;34:90–3. [7] Apard T, Saint-Cast Y. [Malingue’s procedure for digital retraction in Dupuytren’s contracture–principle, modelling and clinical evaluation]. Chir Main 2011;30:31–4.

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[8] Armstrong JR, Hurren JS, Logan AM. Dermofasciectomy in the management of Dupuytren’s disease. J Bone Joint Surg Br 2000;82:90–4. [9] Atroshi I, Strandberg E, Lauritzson A, Ahlgren E, Walden M. Costs for collagenase injections compared with fasciectomy in the treatment of Dupuytren’s contracture: a retrospective cohort study. BMJ Open 2014;4:e004166. [10] Badalamente MA, Hurst LC. Enzyme injection as nonsurgical treatment of Dupuytren’s disease. J Hand Surg Am 2000;25:629–36. [11] Badalamente MA, Hurst LC, Benhaim P, Cohen B. Efficacy and safety of collagenase clostridium histolyticum in the treatment of proximal interphalangeal joints in dupuytren contracture: Combined analysis of 4 phase 3 clinical trials. J Hand Surg Am 2013;38:e54–e5. [12] Badalamente MA, Hurst LC, Hentz VR. Collagen as a clinical target: nonoperative treatment of Dupuytren’s disease. J Hand Surg Am 2002;27:788–98. [13] Bainbridge C, Dahlin LB, Szczypa PP, Cappelleri JC, Guerin D, Gerber RA. Current trends in the surgical management of Dupuytren’s disease in Europe: an analysis of patient charts. Eur Orthop Traumatol 2012;3:31–41. [14] Bainbridge C, Gerber RA, Szczypa PP, Smith T, Kushner H, Cohen B, et al. Efficacy of collagenase in patients who did and did not have previous hand surgery for Dupuytren’s contracture. J Plast Surg Hand Surg 2012;46:177–83. [15] Beard AJ, Trail IA. The ‘‘S’’ Quattro in severe Dupuytren’s contracture. J Hand Surg Br 1996;21:795–6. [16] Beaudreuil J, Lermusiaux JL, Teyssedou JP, Lahalle S, Lasbleiz S, Bernabe B, et al. Multi-needle aponeurotomy for advanced Dupuytren’s disease: preliminary results of safety and efficacy (MNA 1 study). Joint Bone Spine 2011;78:625–8. [17] Betz N, Ott OJ, Adamietz B, Sauer R, Fietkau R, Keilholz L. Radiotherapy in early-stage Dupuytren’s contracture. Long-term results after 13 years. Strahlenther Onkol 2010;186:82–90. [18] Beyermann K, Jacobs C, Prommersberger KJ, Lanz U. [Severe contracture of the proximal interphalangeal joint in Dupuytren’s disease: does capsuloligamentous release improve outcome?]. Handchir Mikrochir Plast Chir 2002;34:123–7. [19] Beyermann K, Prommersberger KJ, Jacobs C, Lanz UB. Severe contracture of the proximal interphalangeal joint in Dupuytren’s disease: does capsuloligamentous release improve outcome? J Hand Surg Br 2004;29:240–3. [20] Breed CM, Smith PJ. A comparison of methods of treatment of pip joint contractures in Dupuytren’s disease. J Hand Surg Br 1996;21:246–51. [21] Brenner P. Dupuytren’s disease of ring and little finger. Orthopedics and Traumatology 2002;10:138–58. [22] Bulstrode NW, Bisson M, Jemec B, Pratt AL, McGrouther DA, Grobbelaar AO. A prospective randomised clinical trial of the intraoperative use of 5-fluorouracil on the outcome of dupuytren’s disease. J Hand Surg Br 2004;29:18–21. [23] Bulstrode NW, Jemec B, Smith PJ. The complications of Dupuytren’s contracture surgery. J Hand Surg Am 2005;30: 1021–5. [24] Chan W-C, Wan S-H, Ip F-K. Review of Partial Fasciectomy for Dupuytren’s Contracture in Southern Chinese Patients. Journal of Orthopaedics, Trauma and Rehabilitation 2012;16:51–4. [25] Chen W, Zhou H, Pan ZJ, Chen JS, Wang L. The role of skin and subcutaneous tissues in Dupuytren’s contracture: an electron microscopic observation. Orthop Surg 2009;1:216–21. [26] Chignon-Sicard B, Georgiou CA, Fontas E, David S, Dumas P, Ihrai T, et al. Efficacy of leukocyte- and platelet-rich fibrin in wound healing: a randomized controlled clinical trial. Plast Reconstr Surg 2012;130:819e–29e.

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