
==== Front
Arch Orthop Trauma Surg
Arch Orthop Trauma Surg
Archives of Orthopaedic and Trauma Surgery
0936-8051
1434-3916
Springer Berlin Heidelberg Berlin/Heidelberg

38653835
5320
10.1007/s00402-024-05320-7
Orthopaedic Surgery
Long-term recurrence of Dupuytren’s disease treated with clostridium histolitycum collagenase. Surgical treatment and anatomopathological study
http://orcid.org/0000-0002-3858-0325
Simón-Pérez C. simonclarisa@yahoo.es

15
http://orcid.org/0000-0002-1162-6063
Rodríguez-Mateos J. I. 2
http://orcid.org/0000-0002-2075-5019
Maestro I. Aguado 1
http://orcid.org/0000-0002-0282-0366
Alvarez-Quiñones M. 3
http://orcid.org/0000-0002-9653-890X
Simon-Perez E. 4
http://orcid.org/0000-0002-7824-5564
Martín-Ferrero M. A. 1
1 https://ror.org/01fvbaw18 grid.5239.d 0000 0001 2286 5329 Discipline of Orthopaedics, University of Valladolid, Valladolid, Spain
2 https://ror.org/05jk45963 grid.411280.e 0000 0001 1842 3755 Department of Plastic Surgery, Hospital Universitario Rio Hortega, Valladolid, Spain
3 https://ror.org/04fffmj41 grid.411057.6 0000 0000 9274 367X Department of Pathological Anatomy, Hospital Clínico Universitario, Valladolid, Spain
4 DP Recoletas Felipe II Hospital C/ Felipe II, Valladolid, 9 47003 Spain
5 https://ror.org/04fffmj41 grid.411057.6 0000 0000 9274 367X Hospital Clínico Universitario, Avenida Ramón y Cajal, s/n, Valladolid, 47005 Spain
23 4 2024
23 4 2024
2024
144 5 20852091
26 12 2023
7 4 2024
© The Author(s) 2024
https://creativecommons.org/licenses/by/4.0/ Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
Objective

To present the functional results obtained and the possible surgical difficulties after the surgical treatment of Dupuytren’s disease (DD) recurrence in patients previously treated with Clostridium histolyticum (CCH) collagenase.

Materials and methods

In this prospective study, 178 patients with DD were treated with CCH from 2011 to 2018; During long-term postoperative follow-up, 34 patients (19.1%) had recurrence of DD. In all patients injected in the IFP the disease recurred; In patients injected in the MCP, recurrence was highest in grade III and IV of the Tubiana classification, with involvement of the 5th finger and the two-finger Y-chord. Fourteen patients (7,8%) required surgery by partial selective fasciectomy due to recurrence of cord DD infiltration. The clinical and functional results of the patients, the difficulty of the surgical technique and the anatomopathological analysis of the infiltrated cords were evaluated in comparison with those of cords and patients who had had no previous CCH treatment.

Results

In all patients, cord rupture was achieved after injection, reducing joint contracture. In 14 patients, we observed during the follow-up the existence of DD recurrence that required surgical treatment by selective partial fasciectomy. There were no major difficulties in surgery and good clinical and functional results at 6 months of follow-up. The anatomopathological study of the resected tissue did not present histological alterations with respect to the samples obtained from patients initially treated by selective partial fasciectomy.

Conclusions

Selective fasciectomy after CCH injection does not lead to important operative difficulties, as long as the CCH injection is performed according to the recommendations. There were no histological changes in the tissue after CCH injection.

Level of evidence

III.

Supplementary Information

The online version contains supplementary material available at 10.1007/s00402-024-05320-7.

Keywords

Collagenase
Clostridium histolyticum
Dupuytren recurrence
Fasciectomy
Universidad de ValladolidOpen Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature.

issue-copyright-statement© Springer-Verlag GmbH Germany, part of Springer Nature 2024
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pmcIntroduction

Dupuytren’s disease (DD) is a progressive fibroproliferative disorder characterized by the development of collagen nodules and cords at the superficial palmar aponeurosis level that causes progressive finger closure [1].

There is no cure definitive for DD, and recurrence and progression of this disease over time are considered unavoidable [1].

Surgery is indicated in DD patients when they have joint contracture of more than 30° at the metacarpo-phalangeal joint (MCP) or any degree of joint contracture at the interphalangeal joint (PIP) [2, 3].

Therapeutic alternatives are selective partial fasciectomy, the most commonly used; percutaneous fasciotomy, with recurrence rates higher than selective partial fasciectomy; early-stage radiation [4, 5], and collagenase from Clostridium histolyticum (CCH), the only pharmacological treatment approved for the treatment of DD [6, 7]. This treatment has been established as an effective and safe modality for the treatment of DD because it reduces the degree of contracture of the affected fingers [7, 8].

DD recurrence is frequent after surgical treatment [9], especially in young patients [1]. The recurrence rate after surgery is highly variable, from 0 to 85%, depending on the patient characteristics, the disease and the type of surgery performed [1].

This variability in the DD recurrence rate is due to the lack of consensus and subjectivity in the definition of recurrence [1, 10]. Felici et al. (2014) defined recurrence as the existence of a passive extension deficit of more than 20° in at least one of the treated joints in the presence of a palpable cord, compared with the results obtained 6–12 weeks before [11].

The surgical treatment of DD has significant morbidity, with an index of complications of approximately 17%, including skin problems, haematoma, nerve damage, and reflex sympathetic dystrophy (CRPS) [12]. In some published studies, the complication index increased to 39% in both the surgical and postoperative stages [13].

There are publications on DD recurrence or progression after CCH injection, the most important factors being age under 60 years, the severity of the disease and the involvement of PIP [14, 15].

Therapeutic alternatives for treating DD recurrence or progression after CCH injection are either reinjection of the CCH or selective palmar fasciectomy on the injected cord [15].

The aim of this study was to evaluate the influence of CCH injection on rescue surgery and the histological changes in the infiltrated cord.

Materials and methods

In a prospective, protocolled study, one hundred seventy-eight patients affected by DD were treated with CCH from 2011 to 2018. Fourteen patients were identified who required surgery by partial selective fasciectomy due to recurrence of cord infiltration after treatment of the disease with CCH.

The inclusion criteria were patients with DD who had previously been injected with CCH toxin, a DD recurrence in the area previously inoculated with a palpable cord, and a joint contracture of at least 30°.

Operative technique

All patients were treated by outpatient surgery and were administered a CCH injection, taking into account the specific doses of both solvent and collagenase required, depending on the joints to be treated, according to the recommendations of the product (Xiapex®). Finger extension and cord rupture were performed after 24–36 h in an outpatient operating room with local-regional anaesthesia or sedation.

The salvage technique after DD recurrence was performed as outpatient surgery with local-regional anaesthesia of the affected limb and local ischaemia. The surgical technique consisted of selective partial fasciectomy of the affected area and zetaplasties, according to the usual technique. We performed anatomical-pathological analysis of the sample obtained.

Assessment

Follow-ups were performed first weekly, then every 2 weeks, every month, every 3 months and every 1 year. In the first reviews, the presence of local complications (haematoma, skin dehiscence, vasculo-nervous lesions, etc.), decreased joint contracture and increased range of motion were evaluated.

Measurements were performed with a standard goniometer assessing joint contracture and range of motion according to the criteria of the International Federation of Societies for Surgery of the Hand (IFSSH).

Defined recurrence as the existence of a passive extension deficit of more than 20° in at least one of the treated joints in the presence of a palpable cord, compared with the results obtained 6–12 weeks before [11].

Statistical study

Quantitative variables are presented with the mean and standard deviation and qualitative variables according to their frequency distribution.

Using Pearson’s Chi-square test, we analysed the association of the qualitative variables. In the event that the number of cells with expected values less than 5 was greater than 20%, we used Fisher’s exact test or the Likelihood Ratio test for variables with more than two categories. We analysed time to recurrence using Kaplan Meier analysis and mortality tables.

We will analyse the data with the statistical software IBM SPSS Statistics version 20.0 for Windows. Values of p < 0.05 will be considered statistically significant.

All patients signed a treatment-specific consent prior to the injection of CCH. The study was approved by the Hospital’s Clinical Research Ethics Committee (PI 17-548- CINV 16–56).

Results

Clinical characteristics and immediate postoperative follow-up

Of the 178 DD patients, 163 were male (91.6%) and 15 were female (8.4%). They were aged between 45 and 89 years, with a mean of 69.8 years; only 12 patients were under 60 years of age (6.7%).

101 patients (were injected in 4º finger (56,7%), 64 patients 5º finger (36,9%) and 13 patients cord Y affecting two fingers. (7,3%)

The classification of patients according to the severity of the disease, the Tubiana classification, is shown in Table 1.

Table 1 The classification of patients according to the severity of the disease, the Tubiana classification

Grades	Angles	Patients	Percentage	
I	1–45º	31	17,4%	
II	46–90º	62	34,8%	
III	91–135º	58	32,6%	
IV	> 135º	27	15,2%	
Total		178	100,0%	

A single injection of CCH was given to all patients; 164 patients (92.1%) were injected in a palpable cord at the MCP level, 151 one finger cord and 13 two finger Y-cord, and 14 patients (7.9%) were injected into a cord at the PIP level.

In all patients, cord rupture was achieved in the surgical act, increasing the range of motion. In one 70-year-old patient, CCH injection was probably not effective due to poor inoculation, and we performed a percutaneous needle fasciotomy to achieve complete cord rupture.

During long-term postoperative follow-up, 34 patients (19.1%) had recurrence of DD, with a mean age of 67.28 years, slightly lower than the mean age of patients without recurrence (69.9 years). In all patients injected in the IFP, the disease recurred; The highest recurrence rates were recorded in 5 patients with involvement of the Y-chord of two fingers (35.7%) and in 21 patients with involvement of the 5th finger (32.8%). This result is statistically significant.

Disease severity (Tubiana classification) and recurrence rates during follow-up were higher in patients with Tubiana grade IV 20 patients (74.1%) and grade III 13 patients (22.4%) being statistically significant. In grade II there was no recurrence in any patient and in one patient with grade I (3.2%).

During long-term postoperative follow-up, only 14 patients (7.8%) presented DD recurrence that required surgical operation, which was done by selective fasciectomy and zetaplasty.

All patients were male and right-handed, and the hand affected was the right in 8 patients. The mean age of 62.5 years (55–70).

All patients were previously punctured at the level of the MCP, six patients at the level of the 4th finger, seven patients at the level of the 5th finger and one patient at the level of a Y-cord between the 4th and 5th fingers.

The follow-up period between the CCH injection and the intervention was between 1 and 10 years with a mean of 5,4 years.

DD recurrence caused less joint contracture than before the puncture of the CCH at the MCP joint in thirteen patients; one patient had a somewhat greater progression, probably due to the difficulty of inoculating the CCH when the cord was not clearly palpated; in twelve patients, the progression of DD at the PIP joint of the treated finger was greater than before the CCH injection (Table 2).

Table 2 Degree of joint contracture of MCP and IFP of the hand prior to CCH injection (Initial) and prior to selective palmar fasciectomy (Recurrence)

Patients	MCP pre CCH	MCP pre F	IFP pre CCH	IFP pre F	
1	75	45	50	85	
2	25	30	0	10	
3	25	10	0	60	
4	30	30	70	35	
5	80	65	0	30	
6	90	75	10	15	
7	95	55	10	20	
8	50	40	10	30	
9	65	50	10	15	
10	95	70	0	30	
11	45	35	10	40	
12	70	35	35	30	
13	90	60	20	10	
14	85	45	10	25	
	65,7	46,1	16,8	31,1	

During surgery in these patients, a fibrosis zone was observed at the puncture site level, but it did not create any difficulties for surgery (Fig. 1).

Fig. 1 Selective fasciectomy 50 months after CCH puncture. Macroscopic aspect

In the immediate postoperative period, eight of these operated patients had skin dehiscence in the old puncture area treated by local cures, without problems of secondary scarring. No major local complications were observed (Fig. 2). All patients underwent postoperative rehabilitation with satisfactory functional recovery (Table 3).

Fig. 2 Functional and skin condition of the hand at the 1.5-month postoperative follow-up

Table 3 Mobility arch achieved after selective palmar fasciectomy compared to the degree of joint contracture prior to surgery

Patients	Mobility prior to surgery	Mobility 6 m after selective palmar fasciectomy	
1	50	170	
2	140	180	
3	110	170	
4	105	175	
5	85	160	
6	90	170	
7	105	165	
8	110	170	
9	115	175	
10	80	160	
11	105	160	
12	115	165	
13	110	170	
14	110	170	

The macroscopic aspect of the material removed was not significantly modified compared with the material removed in patients with DD who had selective palmar fasciectomy as their first treatment option, except for an area of fibrosis in the previous puncture site.

The histological study was carried out using haematoxylin-eosin staining of the samples of the excised tissue in patients who had previously been injected with CCH, and advanced fibrosis was observed in all of them, with a fasciculate-nodular disposition, scarce-moderate fibroblastic cellularity, and collagen fibre production (Fig. 3). These samples were compared with samples of tissue removed from patients with DD initially treated by selective fasciectomy, and no difference was observed between the histological lesions of the cases treated conventionally and those that received injection by CCH (Fig. 4).

Fig. 3 Microscopic aspect of the tissue removed after selective fasciectomy in a patient with previous CCH inoculation. A) General appearance of one of the histological sections of the biopsy, showing fibrosis of the palmar fascia (HE 40x). B) 100X: Histological image of the lesion, with predominance of dense fibrosis over a moderate number of fibroblasts (HE 100X). C) 200X and D) 400X: Dense fibrosis with extensive hyalinization, although collagen fibres are also observed (HE 200x and 400x)

Fig. 4 Microscopic histological aspect of tissue removed in a patient with DD initially operated on by selective fasciectomy. A) 40X: General aspect of the biopsied tissue, showing fibrosis of the palmar fascia (HE 40x). B) 100X: Histological image of the lesion, with predominance of dense fibrosis over a moderate number of fibroblasts (HE 100X). C) 200X and D) 400X. At medium and high magnification, abundant collagen fibres are observed, which predominate over fibroblasts (HE 200x and 400x)

Discussion

The therapeutic options for DD treatment are multiple depending on the patient’s characteristics and the disease itself, through surgical treatment: fasciectomies, dermofasciectomies, fasciotomies, and pharmacological treatment, namely, local injection of CCH [16].

CCH is the first pharmacological option approved for the treatment of adult patients with DD, and it avoids the complications associated with surgery [17]. Several published studies confirm the efficacy of CCH in DD, with clinical and functional improvement and rapid recovery in all patients in whom it has been administered [1, 8, 12, 14, 15].

We have observed the safety of CCH administration, since there have been few local complications, all of slight severity and easy resolution; we have not observed any serious local complications (tendon, vascular or nerve damage) or general complications. However, there are publications documenting serious complications such as tendons ruptured by intratendinous puncture and important cutaneous necrosis [18–20]. Compared with surgery, which has a complication rate ranging between 4% and 39% [13], CCH is a treatment with fewer complications and is also less invasive and therefore a good alternative to DD treatment, especially in elderly patients with multiple associated pathologies who are limited in daily activities, in whom surgery leads to an increase in the local and general complications rate [14, 21].

It is important to differentiate between recurrence and progression in DD, especially in patients treated with CCH in a single joint, to determine the actual efficacy of drug treatment, since DD is a progressive disease that can affect other joints over time regardless of treatment [14].

As other publications, we observed in our study that recurrence is higher and statistically significant, at the IFP level, when two fingers are affected, the greater the severity of the disease and in the 5th finger [8, 14, 15].

Patients who have suffered DD recurrence or progression during follow-up are highly satisfied because the degree of retraction of the affected finger is lesser than before the injection in most patients [14, 15].

Only fourteen patients (7.8%) in our study underwent a salvage palmar fasciectomy; compared with that in other publications [15], this number of patients is low, probably because the mean age of the patients in our study was higher, and only 12 patients were under 60 years of age (6.7%). It has been published [14] that younger patients were more likely to have a recurrence, and ten of the patients we operated on were under 65 years of age; Patient 70 years old, with involvement of the MCP and the PIP, it was necessary to perform a percutaneous needle fasciotomy at the MCP level to complete the cord rupture, with recurrence due to inoculation of the defective CCH.

As reported in other studies, in twelve patients the progression of DD in the PIP joint of the treated finger was greater than before the CCH injection [14, 15].

In the patients who required surgery, we observed scarring fibrosis in the area where the product was injected, without difficulty in the surgical technique, taking into account what has been published in other studies [21, 22].

A significant percentage of patients, 57.1%, presented skin dehiscence in the area of the old puncture, which we treated with local dressings without problems for secondary healing, and no major local complications were observed.

The histological study using haematoxylin-eosin staining of samples of removed tissue from patients who had previously been injected with CCH was compared with the staining samples of removed tissue from patients with DD initially treated with selective fasciectomy, and no difference was observed between the histological lesions in conventionally treated cases and those injected with CCH, which was consistent with other findings [23].

Selective fasciectomy after CCH injection does not report important difficulties in the operative act, as long as the CCH injection is performed according to the recommendations. There were no histological changes in the tissue after CCH injection.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Material 1

Author contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Clarisa Simon-Perez, Jose Ignacio Rodríguez-Mateos and Miguel Angel Martin-Ferrero the first draft of the manuscript was written by Clarisa Simon-Perez and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. The authors have no relevant financial or non-financial interests to disclose

Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature.

Declarations

Ethical approval

Written informed consent was obtained from all patients, and ethical approval from the local Hospital Research Ethics Committee (University Hospital of Valladolid, Spain) was obtained. (PI 17-548- CINV 16–56).

Consent to participate

Informed consent was obtained from all individual participants included in the study.

Consent to publish

The authors affirm that human research participants provided informed consent for publication of the images in Figures.

Conflict of interest

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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References

1. Peimer CA Blazar P Coleman S Kaplan FT Smith T Tursi JP Cohen B Kaufman GJ Lindau T Dupuytren contracture recurrence following treatment with collagenase Clostridium Histolyticum (CORDLESS Study): 3-Year Data J Hand Surg Am 2013 38 1 12 22 10.1016/j.jhsa.2012.09.028 23200951
2. Rayan GM Dupuytren disease: anatomy, pathology, presentation and treatment J Bone Joint Surg Am 2007 89 1 189 198 10.2106/00004623-200701000-00026 17256226
3. Smith AC Diagnosis and indications for surgical treatment Hand Clin 1991 7 4 635 642 10.1016/S0749-0712(21)00900-8 1769986
4. Van Rijssen AL Gerbrandy FS Ter Linden H Klip H Werker PM A comparison of the direct outcomes of percutaneous needle fasciotomy and limited fasciectomy for Dupuytren’s disease: a 6-week follow-up study J Hand Surg Am 2006 31 5 717 725 10.1016/j.jhsa.2006.02.021 16713831
5. Keilholz L Seegenschmiedt MH Sauer R Radiotherapy for prevention of disease progression in early-stage Dupuytren’s contracture: initial and long-term results Int J Radiat Oncol Biol Phys 1996 36 4 891 897 10.1016/s0360-3016(96)00421-x 8960518
6. Gilpin D Coleman S Hall S Houstoun A Karrasch J Jones N Injectable collagenase clostridium histolyticum: a new nonsurgical treatment for Dupuytren´s disease J Hand Surg Am 2010 35 12 2027 2038e1 10.1016/j.jhsa.2010.08.007 21134613
7. Badalamente M Development of collagenase treatment for dupuytren disease Hand Clin 2018 34 4 345 349 10.1016/j.hcl.2018.03.004 30012294
8. Martin-Ferrero MA Simón-Pérez C Rodriguez-Mateos JI Garcia B Hernandez R Brotat M Treatment of Dupuytren´s disease using collagenase Clostridium Hystolyticum Rev Esp Cir Ortop Traumatol 2013 57 6 398 402 10.1016/j.recot.2013.07.005 24071041
9. Werker PM Pess GM Van Rijssen AL Denkler K Correction of contracture and recurrence rates of Dupuytren Contracture following invasive treatment: the importance of Clear definitions J Hand Surg Am 2012 37 10 2095 2105 10.1016/j.jhsa.2012.06.032 22938804
10. Kan HJ Verrijp FW Huisstede BM Hovius SE Van Nieuwenhoven CA Selles RW The consequences of different definitions for recurrence of Dupuytren´s disease ( J Plast Reconstr Aesthet Surg 2013 66 1 95 103 10.1016/j.bjps.2012.08.019 23137947
11. Felici N, Marcoccio I, Giunta R, Haerle M, Leclercq C, Pajardi G, Wilbrand S, Georgescu AV, Pess G Dupuytren contracture recurrence project: reaching consensus on a definition of recurrence,(2014.) Handchir Mikrochir Plast Chir, 46(6): 350–354. 10.1055/s-0034-1394420
12. Watt AJ Curtin CM Hentz VR Collagenase injection as nonsurgical treatment of Dupuytren’s disease: 8-year follow-up J Hand Surg Am 2010 35 4 534 539 10.1016/j.jhsa.2010.01.003 20353858
13. Witthaut J Jones G Skrepnik N Kushner H Houston A Lindau TR Efficacy and safety of collagenase clostridyum histolyticum injection for dupuytren contracture: short-term results from 2 open-label studies J Hand Surg Am 2013 38 1 2 11 10.1016/j.jhsa.2012.10.008 23218556
14. Simon-Perez C Alia J Garcia B Rodriguez-Mateos J Brotat M Aguado H Martin-Ferrero MA Factors influencing recurrence and progression of Dupuytren´s disease treated by collagenase Clostridium Histolitycum Int Orthop 2018 42 4 859 866 10.1007/s00264-017-3690-0 29170879
15. Werlinrud J Hansen K Larsen S Lauritsen J Five-year results after collagenase treatment of Dupuytren disease J Hand Surg Eur 2018 43 8 841 847 10.1177/175319341879015
16. Desai SS Hentz VR The tretment of Dupuytren Disease J Hand Surg Am 2011 36 5 936 942 10.1016/j.jhsa.2011.03.002 21527148
17. Bainbridge C Gerber RA Szczypa PP Smith T Kushner H Cohen B Le Hellio Graverand-Gastineau 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 3–4 177 183 10.3109/2000656X.2012.683795 22670890
18. Swanson JW Watt AJ Vedder NB Skin graft loss resulting from collagenase Clostridium Histolyticum Treatment of Dupuytren Contracture: case repor and review of the literature J Hand Surg Am 2013 38 3 548 551 10.1016/j.jhsa.2012.12.007 23391354
19. Zhang AY Curtin CM Hentz VR Flexor tendon rupture after collagenase injection for Dupuytren contracture: case report J Hand Surg Am 2011 36 8 1323 1325 10.1016/j.jhsa.2011.05.016 21705158
20. Hallock CG Skin laceration as a serious adverse sequela of injectable collagenase for dupuytren contracture Plast Reconst Surg 2012 129 1 205e 206e 10.1097/PRS.0b013e3182365e44 22186568
21. Hay DC Louie DL Earp BE Kaplan FT Akelman E Blazar PE Surgical findings in the treatment of Dupuytren,s disease after initial treatment with clostridial collagenase J Hand Surg Eur 2014 39 5 463 465 10.1177/1753193413488305
22. Eberlin KR Kobraei EM Nyame TT Bloom JM Upton J Salvage palmar fasciectomy after initial treatment with Collagenase Clostridium Histolyticum Plast Reconstr Surg 2015 135 6 1000e 1006e 10.1097/PRS.0000000000001282 26017606
23. Sanjuan-Cervero R Carrera-Hueso FJ Vaquero-Perez M Montaner-Alonso D Recurrent Dupuytren’s disease after fasciectomy and collagenase injection are histologically indistinguishable J Hand Surg Eur 2020 45 5 508 512 10.1177/1753193419900483
