Dupuytren's Contracture Treatments

Number: 0800

Table Of Contents

Applicable CPT / HCPCS / ICD-10 Codes


Scope of Policy

This Clinical Policy Bulletin addresses treatments for Dupuytren's contracture for commercial medical plans. For Medicare criteria, see Medicare Part B Criteria.

Collagenase Clostridium Histolyticum (Xiaflex)

  1. Prescriber Specialties

    The medication must administered by a healthcare provider experienced in injection procedures of the hand and in the treatment of Dupuytren’s contracture.

  2. Exclusions

    Coverage will not be provided for cosmetic use (e.g., cellulite reduction treatment).

  3. Criteria for Initial Approval

    Aetna considers collagenase clostridium histolyticum (Xiaflex) injections medically necessary for the treatment of Dupuytren's contracture when all the following criteria are met:

    1. The member has a finger flexion contracture with a palpable cord in a metacarpophalangeal joint or a proximal interphalangeal joint prior to initiating Xiaflex therapy; and
    2. The contracture is at least 20 degrees prior to initiating Xiaflex therapy; and
    3. The member had a positive tabletop test, defined as the inability to simultaneously place the affected finger(s) and palm flat against a table prior to initiating Xiaflex therapy; and
    4. The member will receive up to 3 injections maximum per cord (4 weeks apart) as part of the current treatment.

    Aetna considers Xiaflex experimental and investigational for all other indications, except for Peyronie's disease (see CPB 0007 - Erectile Dysfunction). For additional information, see Experimental and Investigational and Background sections).

  4. Continuation of Therapy

    Aetna considers continuation of collagenase clostridium histolyticum (Xiaflex) injections medically necessary for the treatment of Dupuytren’s contracture when all of the following criteria are met:

    1. The member meets all initial selection criteria; and
    2. The member is continuing with a treatment course for the same cord. For treatment of a new cord or a previously-treated cord following recurrence, member must meet all initial selection criteria; and
    3. The member has received less than 3 injections total per cord (4 weeks apart).

Intralesional Glucocorticoid Injection

Aetna considers intralesional glucocorticoid injection medically necessary in early-stage Dupuytren's for treatment of local tenderness (tenosynovitis) or for rapidly growing palmar nodules.

Ortho-voltage Radiation

Aetna considers ortho-voltage radiation medically necessary for the treatment of early-stage Dupuytren's contracture (stage N, N/I). (Note: stage N: nodules/cords, no extension deficit = flexion deformity; stage N/I: less than or equal to 10 degrees deficit).

Percutaneous Needle Aponeurotomy

Aetna considers percutaneous needle aponeurotomy (also known as percutaneous needle fasciotomy) medically necessary for the treatment of adults with Dupuytren's contracture  if the member has a finger flexion contracture with a palpable cord in a metacarpophalangeal joint or a proximal interphalangeal joint, the contracture is at least 20 degrees and the member had a positive table top test, defined as the inability to simultaneously place the affected finger(s) and palm flat against a table.

Dosage and Administration

Collagenase clostridium histolyticum is available as Xiaflex for intralesional injection as single-use glass vials containing 0.9 mg of collagenase clostridium histolyticum as a sterile, lyophilized powder for reconstitution. Sterile diluent for reconstitution is provided in the package in a single-use glass vial containing 3 mL of 0.3 mg/mL calcium chloride dihydrate in 0.9% sodium chloride.

Dupuytren’s Contracture

  • Xiaflex should be administered by a healthcare provider experienced in injection procedures of the hand and in the treatment of Dupuytren’s contracture.
  • The recommended dose of Xiaflex is 0.58 mg per injection into a palpable Dupuytren’s cord with a contracture of a metacarpophalangeal (MP) joint or a proximal interphalangeal (PIP) joint according to the injection procedure.
  • Each vial of Xiaflex and sterile diluent should only be used for a single injection. If two joints on the same hand are to be treated during a treatment visit, separate vials and syringes should be used for each reconstitution and injection.
  • Up to two joints in the same hand may be treated during a treatment visit.
  • Approximately 24 to 72 hours following an injection, perform a finger extension procedure if a contracture persists.
  • Injections and finger extension procedures may be administered up to 3 times per cord at approximately 4-week intervals.
  • Inject up to two cords in the same hand at a treatment visit. If a person has other cords with contractures, inject those cords at another treatment visit.

Source: Endo Pharmaceuticals, 2022

Experimental and Investigational

Aetna considers the following experimental and investigational (not an all-inclusive list):

  • Anti-tumor necrosis factor therapy
  • Autologous fat grafting
  • Collagenase nanocapsules
  • Combined percutaneous needle aponeurotomy and lipografting for the treatment of adults with Dupuytren's contracture (DC)
  • Continuous slow skeletal traction
  • Cryopreserved placental membrane
  • Dynamic manugraphy for the evaluation of the outcome of d aponeurectomy in persons with DC
  • Extracorporeal shock wave therapy for prevention of the progression as well as for the treatment of DC
  • Hand therapy after collagenase treatment (Note: Finger extension procedures may be necessary following collagenase injections if contractures persist; see Dosing below)
  • Interferon
  • Middle-phalanx excision and ligament reconstruction
  • Night-time splinting / orthosis for all individuals after fasciectomy or dermofasciectomy for DC
  • Peri-operative 192-Ir high dose rate brachytherapy for improving outcomes of aponeurotomy for DC
  • Ultrasound guidance for injection of Xiaflex
  • Ultrasound therapy.


CPT Codes / HCPCS Codes / ICD-10 Codes

Code Code Description

CPT codes covered if selection criteria are met:

20527 Injection, enzyme (eg, collagenase), palmar fascial cord (ie, Dupuytren's contracture)
26040 Fasciotomy, palmar (eg, Dupuytren's contracture); percutaneous
26341 Manipulation, palmar fascial cord (ie, Dupuytren's cord), post enzyme injection (eg, collagenase), single cord
77401 Radiation treatment delivery, superficial and/or ortho voltage, per day

CPT codes not covered for indications listed in the CPB (not all-inclusive):

Continuous slow skeletal traction, hand therapy after collagenase treatment, middle-phalanx excision and ligament reconstruction - no specific code:

0101T Extracorporeal shock wave involving musculoskeletal system, not otherwise specified, high energy
15769 Grafting of autologous soft tissue, other, harvested by direct excision (eg, fat, dermis, fascia)
15770 Graft; derma-fat-fascia
15773 Grafting of autologous fat harvested by liposuction technique to face, eyelids, mouth, neck, ears, orbits, genitalia, hands, and/or feet; 25 cc or less injectate
+15774     each additional 25 cc injectate, or part thereof (List separately in addition to code for primary procedure)
28890 Extracorporeal shock wave, high energy, performed by a physician or other qualified health care professional, requiring anesthesia other than local, including ultrasound guidance, involving the plantar fascia
76942 Ultrasonic guidance for needle placement (eg, biopsy, aspiration, injection, localization device), imaging supervision and interpretation
97012 Application of a modality to 1 or more areas; traction, mechanical
97035 Application of a modality to 1 or more areas; ultrasound, each 15 minutes

Other CPT codes related to the CPB:

20550 Injection(s); single tendon sheath, or ligament, aponeurosis (eg, plantar "fascia")
26045 Fasciotomy, palmar (eg, Dupuytren's contracture); open, partial

HCPCS codes covered if selection criteria are met:

J0775 Injection, collagenase clostridium histolyticum, 0.01 mg [not for cosmetic use (e.g., cellulite reduction treatment)]

HCPCS codes not covered for indications listed in the CPB (not all-inclusive):

Cryopreserved placental membrane, manugraphy - no specific code:

C1717 Brachytherapy source, nonstranded, high dose rate iridium-192, per source
J0135 Injection, adalimumab, 20 mg
J0717 Injection, certolizumab pegol, 1 mg (code may be used for Medicare when drug administered under the direct supervision of a physician, not for use when drug is self-administered)
J1438 Injection, etanercept, 25 mg (code may be used for Medicare when drug administered under the direct supervision of a physician, not for use when drug is self-administered)
J1602 Injection, golimumab, 1 mg, for intravenous use
J1745 Injection, infliximab, excludes biosimilar, 10 mg
J1826 Injection, interferon beta-1a, 30 mcg
J1830 Injection interferon beta-1b, 0.25 mg (code may be used for Medicare when drug administered under direct supervision of a physician, not for use when drug is self-administered)
J9212 Injection, interferon alfacon-1, recombinant, 1 mcg
J9213 Injection, interferon, alfa-2A, recombinant, 3 million units
J9214 Injection, interferon, alfa-2B, recombinant, 1 million units
J9215 Injection, interferon, alfa-N3, (human leukocyte derived), 250,000 IU
J9216 Injection, interferon, gamma 1-b, 3 million units
Q3027 Injection, interferon beta-1a, 1 mcg for intramuscular use
Q3028 Injection, interferon beta-1a, 1 mcg for subcutaneous use
Q5103 Injection, infliximab-dyyb, biosimilar, (Inflectra), 10 mg
Q5104 Injection, infliximab-abda, biosimilar, (Renflexis), 10 mg
Q5109 Injection, infliximab-qbtx, biosimilar, (Ixifi), 10 mg
Q5131 Injection, adalimumab-aacf (idacio), biosimilar, 20 mg
Q5132 Injection, adalimumab-afzb (abrilada), biosimilar, 10 mg
S0145 Injection, pegylated interferon alfa-2a, 180 mcg per ml
S0148 Injection, pegylated interferon alfa-2b, 10 mcg
S9359 Home infusion therapy, antitumor necrosis factor intravenous therapy; (e.g., Infliximab); administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
S9559 Home injectable therapy; interferon, including administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drug and nursing visits coded separately), per diem

ICD-10 codes covered if selection criteria are met:

M72.0 Palmar fascial fibromatosis [when criteria are met]

ICD-10 codes not covered for indications listed in the CPB (not all-inclusive):

D25.0 - D25.9 Leiomyoma of uterus


Dupuytren's disease, a progressive fibro-proliferative disorder, is characterized by nodule formation and contracture of the palmar fascia, and may result in flexion deformity of the fingers and loss of hand function.  The disease is common in men older than 40 years; in persons of Northern European descent; and in persons who smoke, use alcohol, or have diabetes mellitus.  The symptoms of Dupuytren's contracture are often mild and painless and do not require treatment. Patients present with a small, pitted nodule (or multiple nodules) on the palm, and may stay the same for months or years. In some patients, however, it may progress to the next stage, in which cords of fibrous tissue form in the palm and run into the fingers or thumb, eventually, pulling them into a permanently flexed position, making it difficult to perform activities of daily living. 

The disease initially can be managed with observation and non-surgical therapy.  It will regress without treatment in about 10 % of patients.  Injection of steroids into the nodule has been shown to reduce the need for surgery.  Surgical referral should be made when metacarpophalangeal (MCP) joint contracture reaches 30 degrees or when proximal interphalangeal (PIP) joint contracture occurs at any degree.  In-office percutaneous needle aponeurotomy is an alternative to surgery (Trojian and Chu, 2007).

Clostridium Histolyticum Injection

U.S. Food and Drug Administration (FDA)-Approved Indications

  • Xiaflex (collagenase clostridium histolyticum) is indicated for the treatment of adult patients with Dupuytren’s contracture with a palpable cord.
  • Xiaflex (collagenase clostridium histolyticum) is indicated for the treatment of adult men with Peyronie’s disease with a palpable plaque and curvature deformity of at least 30 degrees at the start of therapy.

Collagenases are proteinases that hydrolyze collagen in its native triple helical conformation under physiological conditions, resulting in lysis of collagen deposits. Injection of collagenase clostridium histolyticum (Xiaflex, Endo Pharmaceuticals, Inc.) into a Dupuytren’s cord, which is comprised mostly of collagen, may result in enzymatic disruption of the cord (Endo Pharmaceuticals, 2022).

Swartz and Lalonde (2008) stated that treatment of Dupuytren's disease is offered to symptomatic patients with painful nodular or disabling contracture.  Limited fasciectomy of the involved abnormal structures followed by hand therapy is standard treatment, but it is associated with serious potential complications.  Moreover, recurrence is common.  New treatments include the injection of clostridial collagenase, which works by breaking down the excessive build-up of collagen in the hand.

In a phase II open-label clinical trial, Badalamente and Hurst (2000) examined the clinical safety and effectiveness of clostridial collagenase injection as a non-surgical treatment of Dupuytren's disease.  A total of 35 patients entered the study (3 women and 32 men).  The mean age was 65 years.  The first 6 patients were treated following a dose escalation protocol and received 300, 600, 1,200, 2,400, 4,800, and 9,600 units (U) collagenase injected into the cord that was causing contracture of the MCP joint.  There were no beneficial clinical effects of these injections.  The remaining 29 patients had collagenase injections at a dose level of 10,000 U into cords that are causing contractures of 34 MCP joints, 9 PIP joints, and 1 thumb.  Twenty-eight of the 34 MCP joint contractures corrected to normal extension (0 degrees) and 2 of the 34 MCP joint contractures corrected to 5 degrees of normal extension, with full range of motion, within 1 to 14 days of injection.  In patients with PIP joint contractures, 4 of the 9 joints corrected to normal (0 degrees).  One PIP joint corrected to within 10 degrees of normal and 2 corrected to within 15 degrees of normal.  There were 2 failures; these patients required surgery.  The mean follow-up period was 20.0 +/- 5.6 months for the MCP joints and 14.1 +/- 6.6 months for the PIP joints.  Clostridial collagenase injection of Dupuytren's cords causing MCP and PIP joint contractures appears to have merit as non-surgical treatment of this disorder.  The authors stated that pending further placebo, double-blind studies, collagenase injection to treat Dupuytren's disease may be a safe and effective alternative to surgical fasciectomy.

Badalamente et al (2002) reported that in a series of controlled phase II clinical trials, excessive collagen deposition in Dupuytren's disease has been targeted by a unique non-operative method using clostridial collagenase injection therapy to lyse and rupture finger cords causing MCP and/or PIP joint contractures.  A total of 49 patients were treated in a random, placebo-controlled trial of one dose of collagenase versus placebo at 1 center.  Subsequently 80 patients were treated in a random, placebo-controlled, dose-response study of collagenase at 2 test centers.  The results of these studies indicated that non-operative collagenase injection therapy for Dupuytren's disease is both a safe and effective method of treating this disorder in the majority of patients as an alternative to surgical fasciectomy.

In a prospective, randomized, double-blind, placebo-controlled, multi-center study, Hurst et al (2009) examined the effects of injectable collagenase clostridium histolyticum for the treatment of Dupuytren's contracture.  These investigators enrolled 308 patients with joint contractures of 20 degrees or more .  The primary MCP or PIP joints of these patients were randomly assigned to receive up to 3 injections of collagenase clostridium histolyticum (at a dose of 0.58 mg per injection) or placebo in the contracted collagen cord at 30-day intervals.  One day after injection, the joints were manipulated. The primary end point was a reduction in contracture to 0 to 5 degrees of full extension 30 days after the last injection.  Twenty-six secondary end points were evaluated, and data on adverse events were collected.  Collagenase treatment significantly improved outcomes.  More cords that were injected with collagenase than cords injected with placebo met the primary end point (64.0 % versus 6.8 %, p < 0.001), as well as all secondary end points (p < or = 0.002).  Overall, the range of motion in the joints was significantly improved after injection with collagenase as compared with placebo (from 43.9 to 80.7 degrees versus from 45.3 to 49.5 degrees, p < 0.001).  The most commonly reported adverse events were localized swelling, pain, bruising, pruritus, and transient regional lymph-node enlargement and tenderness.  Three treatment-related serious adverse events were reported: 2 tendon ruptures and 1 case of complex regional pain syndrome.  No significant changes in flexion or grip strength, no systemic allergic reactions, and no nerve injuries were observed.  The authors concluded that collagenase clostridium histolyticum injection significantly reduced contractures and improved the range of motion in joints affected by advanced Dupuytren's disease.

On February 2, 2010, the Food and Drug Administration approved collagenase clostridium histolyticum (Xiaflex) as the first drug to treat Dupuytren's contracture.  Xiaflex is injected directly into the collagen cord of the hand and should be administered only by a health care professional experienced with injections of the hand, because tendon ruptures may occur.  The product insert of Xiaflex states that injections may be administered up to 3 times per cord at approximately 4-week intervals.  Up to two cords may be injected at a time.  If patients have other cords with contractures of MCP or PIP joints, these cords should be injected in sequential order.

The most common adverse reactions reported in 25% or more of patients treated with Xiaflex and at an incidence greater than placebo were edema peripheral (e.g., swelling of the injected hand), contusion, injection site hemorrhage, injection site reaction, and pain in the injected extremity. In the controlled portions of the clinical trials in Dupuytren’s contracture (Studies 1 and 2), a greater proportion of Xiaflex-treated patients (15%) compared to placebo-treated patients (1%) had mild allergic reactions (pruritus) after up to 3 injections. The incidence of Xiaflex-associated pruritus increased after more Xiaflex injections in patients with Dupuytren’s contracture. (Endo Pharmaceuticals, 2022).

Intralesional Steroid Injection

Ball and colleagues (2016) Dupuytren's disease is a common fibrotic disorder of the palm characterized by the development of progressive flexion deformities in the digits, leading to significant functional impairment.  Surgical excision remains the most common treatment.  However, this is only indicated in patients with established contractures rather than those with early disease.  Early disease is generally characterized by the presence of palmar nodules with limited or no contracture of the fingers.  The ideal treatment would be directed at patients with early progressive disease to prevent future deterioration.  Various non-surgical treatment modalities have been described but there is currently no systematic assessment of the role and effectiveness of these treatments in patients with early disease.  Using a PICOS analysis, these investigators reviewed publications of studies of patients with early disease who had received physical therapies, pharmacological treatment, or radiotherapy.  Following PRISMA guidelines titles and abstract were screened using pre-defined criteria to identify those reporting outcomes specifically relating to the treatment of early disease.  In the absence of a definition of early disease studies were included if early Dupuytren's disease (DD) was described clinically, with digital contractures not exceeding 30°, Tubiana grades N to 1, and which reported identifiable data.  Studies were excluded if data for early Dupuytren's disease patients could not be extracted for analysis.  In this systematic review, a total of 26 studies were identified and analyzed to evaluate the effect of pharmacological therapy (n = 11), physical therapy (n = 5) and radiotherapy (n = 10) on early Dupuytren's disease.  The studies comprised 20 case series, 1 cohort study with the remainder reporting case studies.  All publications were graded level of evidence IV or V assessed using the Oxford Centre for Evidence Based Medicine grading.  Narrative descriptions of the data were presented.  The authors concluded that physical therapies were the most robustly assessed, using objective measures but the studies were under-powered, providing insufficient evidence of efficacy.  Intralesional steroid injection and radiotherapy appeared to lead to softening of nodules and to retard disease progression, but lacked rigorous evaluation and studies were poorly designed.  These researchers stated that there is an urgent need for adequately powered, double-blinded, randomized trials for this common disorder which affects 4 % of the population.

An UpToDate review on “Dupuytren's contracture” (Aggarwal and Blazar, 2017) states that "[i]ntralesional glucocorticoid injection with triamcinolone acetonide and lidocaine hydrochloride may be helpful if local tenderness is bothersome (eg, the patient develops tenosynovitis) or if the palmar nodule is growing rapidly. ....Glucocorticoid injection is helpful in patients with more recent disease onset; cords with or without significant contracture do not respond to glucocorticoid injection." Regarding use of glucocorticoids as a treatment for flexion contractures, the review stated that “[o]ther interventions, including continuous slow skeletal traction, dimethyl sulfoxide, vitamin E, allopurinol, physical therapy, ultrasound therapy, glucocorticoid injections, interferon, and splinting, have generally not been successful.”

Management of Recurrent Dupuytren Contracture

Wong et al (2021) stated that with numerous treatment modalities available, it is unclear if the treatment of recurrent Dupuytren disease is as effective as its initial treatment.  These investigators examined the outcomes of management of recurrent DC.  Adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, Medline, Embase, PubMed, CINAHL, and Cochrane Central Register of Controlled Trials were searched from their inception to April 2020.  Studies of patients aged 18 years or older undergoing treatment for recurrent DC were included.  The risk of bias in non-randomized studies of interventions tool was used for quality assessment.  This systematic review identified 12 studies: 311 patients with 224 affected digits-index (n = 5; 2.2 %), long (n = 17; 7.6 %), ring (n = 57; 25.4 %), small (n = 112; 50 %), and unspecified (n = 33; 14.7 %); of these, there were 76 MCP joints (45.5 %), 90 PIP joints (53.9 %), and 1 distal interphalangeal (DIP) joint (0.6 %).  Previous treatment included the following: percutaneous needle aponeurotomy (n = 103 of 311 patients; 33.1 %), collagenase clostridium histolyticum-injection (CCH; n = 75 of 311; 24.1 %), limited fasciectomy (LF) ± skin graft (n = 83 of 311; 26.7 %), fasciotomy (n = 1 of 311; 0.3 %), and unspecified (n = 64 of 311; 20.6 %).  Recurrence was treated by percutaneous needle aponeurotomy (n = 68 of 311 patients; 21.9 %); CCH injection (n = 53 of 311; 17.0 %); aponeurotomy or dermo-fasciectomy or LF (n = 176 of 311; 56.6 %); ray/digit amputation (n = 8 of 311; 2.6 %); and PIPJ arthrodesis (n = 6 of 293; 2.0 %); ROM was improved by 23.31° (95 % CI: 13.13° to 33.50°; I2 = 67 %; p = 0.05) and 15.49 ° (95 % CI: 2.67° to 28.31°; I2 = 76 %; p = 0.01) for MCPJ and PIPJ, respectively.  The authors concluded that there is low level of evidence that both surgical and non-surgical treatments provided clinically important improvements for recurrent DC.  These researchers stated that currently, the choice of treatment for recurrent disease remains a balance between both patient and physician preference.  They stated that future steps should focus on consensus of a universal definition for recurrent DC to allow standardized comparison of treatments, complete outcome data reporting, as well as conducting higher level evidence studies to examine treatment effectiveness for recurrent DC.

The authors stated that this study had several drawbacks.  First, the methodological quality of included studies ranged from low-to-moderate, indicating a moderate risk of bias in the results.  Second, the generalizability of the outcomes is inherently limited given the lack of universal definition for recurrence.  Without a clinical definition, it is difficult to determine the effect of baseline differences in patients, which are an important factor in surgeons’ discretion for treatment . Third, there is inconsistency in outcomes reported across studies.  This posed as a barrier when results were pooled for meta-analysis.  Fourth, length of follow-up was variable across studies; with insufficient follow-up, secondary recurrences, ROM, and contracture could not be accurately documented.  Finally, the meta-analysis combined outcomes of both surgical and conservative modalities without subgroup analysis within each group.  The heterogeneous nature of this analysis made it difficult to compare if specific modalities of treatments within each group were superior or non-inferior.  For instance, despite surgery being effective for improving ROM for patients with DC, it is not possible to comment if limited fasciectomy or fasciotomy would provide better results.  As such, only a general impression of outcomes of treating recurrent DC can be made.

Percutaneous Needle Aponeurotomy

Another treatment of Dupuytren's contracture (DC) is injection of steroids into the nodule; and has been shown to reduce the need for surgery.  Surgical referral should be made when MCP joint contracture reaches 30 degrees or when PIP joint contracture occurs at any degree.  In-office percutaneous needle aponeurotomy is an alternative to surgery (Trojian and Chu, 2007).

Manet and associates (2011) stated that DC is a retractile fibrosis of the superficial palmar aponeurosis of the hand, resulting in a progressive and fixed flexion of the fingers that may result in severe limitation of hand function.  It affects several millions of people in Europe and North America.  Risk factors are genetic and sometimes related to mellitus diabetes.  There is no spontaneous remission.  Until recently, surgery was the only treatment, but now needle aponeurotomy emerges as a therapeutic alternative.  It should be performed as first-line treatment by a trained practitioner.  Short-term and long-term results of needle aponeurotomy appear identical to those of surgery, with milder complications.  It is indicated in palmar, palmo-digital, as well as in strictly digital forms of the disorder.

In a review on percutaneous needle aponeurotomy, Foucher and colleagues (2003) reviewed the charts of 211 patients treated consecutively on 261 hands and 311 fingers to assess the rate of post-operative complications.  The first 100 patients were evaluated with a mean follow-up of 3.2 years to assess the rate of recurrences and extension of the disease.  In the whole group the mean age was 65 years and delay between onset and treatment was 6 years.  Division of the cords were performed only in the palm in 165 cases, in the palm and finger in 111 and purely in the finger in 35.  Complications were scarce without infection or tendon injury but 1 digital nerve was found injured during a second procedure.  Post-operative gain was prominent at MCP joint level (79 % versus 65 % at interphalangeal level).  The re-operation rate was 24 %.  In the group assessed at 3.2 years follow-up, the recurrence rate was 58 % and disease "activity" 69 %.  Fifty-nine hands need further surgery.  The ideal indication for this simple and reliable technique is an elderly patient with a bowing cord and predominant MP contracture.

Cheng et al (2008) reviewed the safety and effectiveness of needle aponeurotomy for DC in Chinese patients.  A total of 7 men and 1 woman aged 50 to 80 (mean of 67) years underwent needle aponeurotomy for DC.  Five were manual workers and the other 3 were retired.  Their chief complaints were difficulty moving the fingers, clumsiness of the hand, and occasional pain in the palm.  No patient had any family history of DC.  A total of 41 points were released in 13 fingers (3 middle, 3 ring, and 7 little).  Immediately after release, the mean flexion contracture correction of the MCP and PIP joints were 50 (from 50 to 0) and 35 (from 46 to 11) degrees, respectively.  At 22-month follow-up, the mean residual flexion contracture of both joints were 12 and 27 degrees; the corresponding long-term improvements were 70 and 41 %, respectively.  No patient had a wound complication or neurovascular injury.  All had a normal score for Disabilities of the Arm, Shoulder, and Hand.  The authors concluded that for Chinese patients with DC, needle aponeurotomy is safe and effective.  Long-term correction is better maintained in MCP than PIP joints (70 % versus 41 %).

Lellouche (2008) stated that DC or Dupuytren's disease of the hand is the retraction of the palmar aponeurosis.  Its course is progressive and leads to an irreducible flexion deformity of one or more fingers.  Early diagnosis is necessary for the table test, which determines the need for treatment.  Needle aponeurotomy should be the first option treatment.  This minimally invasive out-patient procedure minimizes sick leave and does not require immobilization or physical therapy.  Several studies confirmed the short-term and intermediate-term effectiveness of this treatment and the minimal side effects when performed by experienced operators.  Multiple procedures for extensive disease (several knots) can be performed in the hospital.  Close medical and surgical collaboration is necessary for treatment of severe forms, treatment failures, and multiple recurrences.

Guidance from the National Institue for Clinical Excellence (NICE, 2004) concluded: "Current evidence on the safety and efficacy of needle fasciotomy for Dupuytren’s contracture appears adequate to support the use of the procedure, provided that normal arrangements are in place for consent, audit and clinical governance."  The guidance explained that the main benefit offered by this procedure is a short-term reduction in the degree of contracture.  The guidance stated that the evidence shows that the recurrence rate is approximately 50 % at 3 to 5 years and seems to depend on the severity of the disease.  The guidance stated that some data suggest that individuals with less severe disease or with metacarpophalangeal joint contracture benefited most from this procedure.

Sanjuan Cervero et al (2013) compared the use of direct health resources and costs generated in the treatment of DC using 2 different techniques:
  1. subtotal fasciectomy and
  2. infiltration with collagenase clostridium histolyticum (CCH) in regular clinical practice. 

Observational, retrospective study based on data from the computerized clinical histories of 2 groups of patients:

  1. those treated surgically using a 1- or 2-digit subtotal fasciectomy technique (FSC) and
  2. 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.  A total of 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 DC with subtotal FSC amount to €1,814 for major ambulatory surgery and €1,961 with hospital stay including admission, surgical intervention (€904), examinations, dressings and physiotherapy.  As to collagenase infiltration, costs amount to €952 (including minor surgery admission, vial with product, office examination and dressings).  Finally, comparing total costs for treatments, a savings of €388 is estimated in favor of CCH treatment in the best-case scenario (patient under MAS system with no need for physiotherapy) and €1,008 in the worst-case scenario (patient admitted to hospital needing subsequent physiotherapy), implying a savings of 29 % and 51 %, respectively.  The authors concluded that this study demonstrated that treating patients with DC by injection with CCH generated a total savings of 29 % and 51 % (€388 and €1008) compared with fasciectomy at the time of treatment.  Moreover, they stated that long-term evolution of CCH treatment is uncertain and the recurrence rate unknown.

In a retrospective cohort study, Atroshi et al (2014) compared CCH injections and FSC for DC regarding actual total direct treatment costs and short-term outcomes.  Patients aged 65 years or older with previously untreated DC of 30° or greater in the MCP and/or PIP joints of the small, ring or middle finger were included in this study.  The CCH group comprised 16 consecutive patients treated during the first 6 months following the introduction of CCH as treatment for DC at the study center.  The controls were 16 patients randomly selected among those operated on with FSC at the same center during the preceding 3 years.  Treatment with CCH was given during 2 standard outpatient clinic visits (injection of 0.9 mg, distributed at multiple sites in a palpable cord, and next-day finger extension under local anesthesia) followed by night-time splinting.  Fasciectomy was carried out in the operating room (day surgery) under general or regional anesthesia using standard technique, followed by therapy and splinting.  Outcome measures included actual total direct costs (salaries of all medical personnel involved in care, medications, materials and other relevant costs), and total MCP and PIP extension deficit (degrees) measured by hand therapists at 6 to 12 weeks after the treatment.  Collagenase injection required fewer hospital outpatient visits to a therapist and nurse than FSC.  Total treatment cost for CCH injection was US$1,418.04 and for FSC US$2,102.56.  The post-treatment median (IQR) total extension deficit was 10 (0 to 30) for the CCH group and 10 (0 to 34) for the FSC group.  The authors concluded that treatment of DC with 1 CCH injection cost 33 % less than FSC with equivalent effectiveness at 6 weeks regarding reduction in contracture.

Peimer et al (2013) evaluated long-term safety and effectiveness of CCH after the 3rd year of a 5-year non-treatment follow-up study (Collagenase Option for Reduction of Dupuytren Long-Term Evaluation of Safety Study [CORDLESS study]).  This study enrolled DC patients from 5 previous clinical studies.  Beginning 2 years after the 1st CCH injection, these investigators re-evaluated patients annually for joint contracture and safety.  Recurrence in a previously successfully treated joint (success = 0° to 5° contracture after CCH administration) was defined as 20° or greater worsening in contracture in the presence of a palpable cord or medical/surgical intervention to correct new or worsening contracture. We assessed partially corrected joints (joints reduced 20° or more from baseline contracture but not to 0° to 5°) for nondurable response, also defined as 20° or greater worsening of contracture or medical/surgical intervention.  Of 1,080 CCH-treated joints (648 MCP; 432 PIP; n = 643 patients), 623 (451 MCP, 172 PIP) had achieved 0° to 5° contracture in the original study.  Of these joints, 35 % (217 of 623) recurred (MCP 27 %; PIP 56 %).  Of these recurrences, an intervention was performed in 7 %.  Of the 1,080 CCH-treated joints, 301 were partially corrected in the original study.  Of these, 50 % (150 of 301; MCP: 38 % [57 of 152]; PIP: 62 % [93 of 149]) had non-durable response.  These researchers identified no new long-term or serious adverse events attributed to CCH during follow-up.  Anti-clostridial type I collagenase and/or anti-clostridial type II collagenase antibodies were reported for 96 % or more of patients who received 2 or more CCH injections and 82 % who received 1 injection.  The authors concluded that recurrence rate, which is comparable to other standard treatments, and the absence of long-term adverse events 3 years after initial treatment indicated that CCH is safe and effective treatment for DC.  Most successfully treated joints had a contracture well below the threshold for surgical intervention 3 years after treatment.  Recurrence rates among successfully treated joints were lower than non-durable response rates among partially corrected joints.


Prophylactic external beam radiation therapy (RT) has been reported to prevent disease progression in early-stage DC.

Keilholz et al (1996) evaluated initial response, long-term outcome, as well as treatment toxicity of RT for the prevention of disease progression in early-stage DC.  A total of 96 patients (142 hands) received ortho-voltage RT, which consisted of 2 courses with daily fractionation of 5 x 3 Gy (total dose of 30 Gy) separated by a 6-week interval.  The extent of disease was staged according to the Tubiana's classification.  Initial evaluation was performed 3 months after completion of RT; long-term outcome was analyzed at last follow-up.  The mean follow-up was 6 +/- 2 (range of 1 to 12) years.  Fifty-seven patients with a minimum follow-up of 5 (median 7.5; mean of 9.5 to 12) years were separately evaluated for long-term outcome (i.e., prevention of disease progression).  Acute and late treatment toxicity was assessed using the Radiation Therapy Oncology Group/EORTC criteria.  According to stage, 130 cases (92 %) remained stable at 3 months follow-up, 10 improved (7 %), and 2 progressed (1 %).  An objective reduction of symptomatic cords and nodules was achieved in 107 cases (75 %) at 3 months follow-up.  Moreover, 87 % of the patients reported a subjective relief of symptoms.  In long-term follow-up, only 16 of 142 cases (11 %) had progressed according to stage.  In the group with minimum follow-up 5 years (n = 57), 44 patients (77 %) experienced no disease progression, whereas 13 progressed (23 %) inside [8 cases (14 %)] or outside [5 cases (9 %)] of the RT field.  Most failures could have been avoided with appropriate choice of larger safety margins included in the treated portals; however, the failures outside were still amenable for another RT course.  The authors concluded that RT is effective to prevent disease progression for early-stage DC, which helps to avoid an otherwise necessary surgical procedure that is performed in advanced stages of DC.

Seegenschmiedt et al (2001) presented the 1-year results of a prospective randomized trial that compared two different RT dose concepts for early-stage DC.  A total of 129 patients (62 females; 67 males) were entered in this study: 69 had bilateral and 60 unilateral involvement of DC accounting for 198 irradiated hands.  According to Tubiana's classification, 73 hands had Stage N (nodules/cords, no extension deficit = flexion deformity), 61 had Stage N/I (less than or equal to 10 degrees deficit), 59 had Stage I (11 to 45 degrees deficit), and 5 had Stage II (46 to 90 degrees deficit) DC.  Prophylactic RT was randomly delivered; in Group A, 63 patients (95 hands) received 10 x 3 Gy (total dose of 30 Gy) in 2 series (5 x 3 Gy) separated by 8 weeks; in Group B, 66 patients (103 hands) received 7 x 3 Gy (total dose of 21 Gy) in 1 series within 2 weeks.  Ortho-voltage RT (120 kV) was applied using standard cones and individual shielding of un-involved areas of the palm.  Relevant patient and disease parameters were equally distributed in both groups.  Evaluation (toxicity, efficacy) was performed at 3 and 12 months after RT.  Subjective (patient's opinion) and objective parameters (measurements, palpation, and comparative photographs) were applied to assess treatment response.  Minimum follow-up was 1 year.  Acute toxicity was minimal, but slightly more pronounced in Group B.  Seventy-six (38 %) hands developed skin reactions common toxicity criteria [CTC] 1 degrees (A, 30; B, 46); and 12 (6 %) had skin reactions CTC 2 degrees (A, 4; B, 8).  Chronic side effects were limited to dryness, desquamation, skin atrophy, and change of sensation (LENT 1 degrees ) in 9 (5 %) sites without differences between the two groups.  At 3 and 12 months after RT, subjective and objective reduction of symptoms, nodules, and cords occurred in both groups (p < 0.01) with no differences between the groups: in Group A, 55 (56 %) sites regressed, 35 (37 %) remained stable, and 7 (7 %) progressed, whereas in Group B, 55 (53 %) regressed, 39 (38 %) remained stable, and 9 (9 %) progressed at 12-month follow-yp (non-significant).  Overall and mean number of nodules, cords, and skin changes decreased at 3 and 12 months.  The "treatment failure" rate at 1 year was 16 of 198 (8 %), but only 4 (2 %) sites required hand surgery for disease progression.  Seven of 60 patients with unilateral DC received prophylactic RT for the initially un-involved, contralateral hand due to progression of DC.  The authors concluded that both prophylactic RT concepts have been well-accepted and well-tolerated by patients.  Within the first year, they were equally effective to prevent further disease progression of DC and obtain considerable symptomatic improvement.  Although 1-year results suggested similar response rates for both treatment groups, long-term follow-up of greater than 5 years has to be awaited for final assessment and recommendation of an optimized RT treatment schedule.

In a retrospective analysis, Betz et al (2010) reported the long-term outcome and late toxicity of RT to prevent disease progression in patients with early-stage DC.  A total of 135 patients (208 hands) were irradiated with ortho-voltage (120 kV; 20 mA; 4-mm Al filter) in 2 courses with 5 daily fractions of 3.0 Gy to a total dose of 30 Gy; separated by a 6- to 8-week interval.  The extent of disease was described according to a modified Tubiana's classification.  Long-term outcome was analyzed at last follow-up with a median follow-up of 13 years (range of 2 to 25 years).  Late treatment toxicity and objective reduction of symptoms as change in stage and numbers of nodules and cords were evaluated and used as evidence to assess treatment response.  According to the individual stages, 123 cases (59 %) remained stable, 20 (10 %) improved, and 65 (31 %) progressed.  In stage N 87 % and in stage N/I 70 % remained stable or even regressed.  In more advanced stages, the rate of disease progression increased to 62 % (stage I) or 86 % (stage II).  A total of 66 % of the patients showed a long-term relief of symptoms (i.e., burning sensations, itching and scratching, pressure and tension).  Radiotherapy did not increase the complication rate after surgery in case of disease progression and only minor late toxicity (dry desquamation, skin atrophy) could be observed in 32 % of the patients.  There was no evidence for a second malignancy induced by RT.  The authors concluded that after a mean follow-up of 13 years, RT is effective in prevention of disease progression and improves patients' symptoms in early-stage DC (stage N, N/I).  In case of disease progression after RT, a "salvage" operation is still feasible.

In a systematic review, Kadhum and colleagues (2017) examined the evidence on the use of radiotherapy in Dupuytren's disease.  Only 6 articles met a minimum set standard, 5 of which were retrospective cohort studies and 1 a RCT.  A total of 770 Dupuytren's hands, nearly all with Tubiana stage 0 to 1 disease, were irradiated with an average 30 Gy.  Disease regression ranged from 0 % to 56 %, stability from 14 % to 98 % and progression from 2 % to 86 %.  Salvage surgery was successful in all cases of disease progression post-radiotherapy.  There were no reports of adverse wound healing problems associated with such surgery or radiotherapy-associated malignancy.  The authors concluded that radiotherapy should be considered an unproven treatment for early Dupuytren's disease due to a scarce evidence base and unknown long-term adverse effects.  They stated that well-designed RCTs are needed to confirm the benefits of radiotherapy treatment.

An UpToDate review on “Dupuytren's contracture” (Aggarwal and Blazar, 2017) states that “Prophylactic external beam radiation therapy can prevent progression and can provide symptomatic benefit in patients with mild to moderate flexion deformities; however, no controlled studies have been published”.

Guidance from the National Institute for Health and Care Excellence (NICE, 2016) concluded that "[t]he evidence on radiation therapy for early Dupuytren's disease raises no major safety concerns. Current evidence on its efficacy is inadequate in quantity and quality, and is difficult to interpret because of uncertainty about the natural history of Dupuytren's disease."

Investigational Therapies

An UpToDate review on “Dupuytren's contracture” (Aggarwal and Blazar, 2019) states that “Other interventions, including continuous slow skeletal traction … ultrasound therapy, interferon, and splinting, have generally not been successful”.

Anti-Tumor Necrosis Factor Therapy

Nanchahal and colleagues (2018) noted that Dupuytren's disease is a common fibrotic condition of the hand that causes irreversible flexion contractures of the fingers, with no approved therapy for early stage disease; their previous analysis of surgically-excised tissue defined tumor necrosis factor (TNF) as a potential therapeutic target.  In a randomized, dose-response, proof-of-concept, phase-IIa clinical trial, these researchers examined the efficacy of injecting nodules of Dupuytren's disease with a TNF inhibitor.  Patients were randomized to receive adalimumab on 1 occasion in dose cohorts of 15 mg in 0.3 ml, 35 mg in 0.7 ml, or 40 mg in 0.4 ml, or an equivalent volume of placebo in a 3:1 ratio.  Two weeks later the injected tissue was surgically excised and analyzed.  The primary outcome measure was levels of mRNA expression for α-smooth muscle actin (ACTA2).  Secondary outcomes included levels of α-SMA and collagen proteins.  A total of 28 patients were recruited, 8 assigned to the 15-mg, 12 to the 35-mg and 8 to the 40-mg adalimumab cohorts.  There was no change in mRNA levels for ACTA2, COL1A1, COL3A1 and CDH11.  Levels of α-SMA protein expression in patients treated with 40-mg adalimumab (1.09 ± 0.09 ng per μg of total protein) were significantly lower (p = 0.006) compared to placebo treated patients (1.51 ± 0.09 ng/μg).  The levels of procollagen type I protein expression were also significantly lower (p < 0.019) in the sub-group treated with 40-mg adalimumab (474 ± 84 pg/μg total protein) compared with placebo (817 ± 78 pg/μg).  There were 2 serious AEs, both considered unrelated to the study drug.  The authors concluded that in this dose-ranging study, injection of 40-mg of adalimumab in 0.4 ml resulted in down-regulation of the myofibroblast phenotype as evidenced by reduction in expression of α-SMA and type I procollagen proteins at 2 weeks.  These data formed the basis of an ongoing phase-IIb clinical trial (n = 138) assessing the efficacy of intra-nodular injection of 40-mg adalimumab in 0.4 ml compared to an equivalent volume of placebo in patients with early stage Dupuytren's disease.

Autologous Fat Grafting

Tuncel and co-workers (2017) described their experience with treating DD (17 patients; 18 hands) using needle aponeurotomy and non-centrifuged autologous fat grafting.  Patients were treated with needle aponeurotomy and non-centrifuged autologous fat graft under general anesthesia.  The fat grafts were injected into the surgical area so as to stay in contact with the operated site.  An extension splint was used for 1 week post-operatively and the patients received hand therapy for 3 weeks.  Before the treatment, the contracture in the proximal interphalangeal and metacarpophalangeal joints was a mean of 45.06 ± 13.44 degrees and 36.56 ± 13.09 degrees, respectively.  It was 1.61 ± 1.65 and -0.56 ± 3.78 degrees at 3 months, respectively.  The difference between these measurements was statistically significant.  The mean follow-up period was 12 months.  The results were satisfactory and no complications were observed during the follow-up period.  The authors concluded that percutaneous aponeurotomy with non-centrifuged autologous fat grafting was found to have significantly beneficial effects in the treatment of DD.  This was a small study (n = 17 patients); these preliminary findings need to be further validated.

Collagenase Nanocapsules

Villegas and associates (2018) noted that fibrosis is a common lesion in different pathologic diseases and defined by the excessive accumulation of collagen.  Different approaches have been used to treat different conditions characterized by fibrosis.  The FDA and EMA approved the use of collagenase to treat palmar fibromatosis (Dupuytren's contracture).  The EMA approved additionally its use in severe Peyronie's disease, but it has been used off-label in other conditions.  The approved treatment includes up to 3 (in palmar fibromatosis) or up to 8 (in penile fibromatosis) injections followed by finger extension or penile modeling procedures, typically causing severe pain.  Frequent single injections are adequate to treat palmar fibromatosis.  The need to repeatedly inject doses of this enzyme can be due to the labile nature of collagenase, which exhibits a complete activity loss after a short period of time. 

Villegas, et al. (2018) presented a novel strategy to manage this enzyme based on the synthesis of polymeric nanocapsules that contain collagenase encapsulated within their matrix.  These nanocapsules have been engineered for achieving a gradual release of the encapsulated enzyme for a longer time, which can be up to 10 days.  The efficacy of these nanocapsules has been tested in a murine model of local dermal fibrosis, and the results demonstrated a reduction in fibrosis greater than that with the injection of free enzyme; this type of treatment showed a significant improvement compared to conventional therapy of free collagenase.  The authors concluded that these findings indicated a high potential for this novel system to improve the current treatment for fibrotic diseases.

Combined Aponeurectomy and Peri-Operative 192-Ir High Dose Rate Brachytherapy for the Treatment of Dupuytren's Contracture

Ciernik and colleagues (2021) noted that partial aponeurectomy (PA) is a standard procedure for DC.  These investigators reported a novel approach using surgery combined with peri-operative high dose rate (192-Ir HDR) brachytherapy.  From March 2018 until February 2020, a total of 13 rays of 6 patients with DCs underwent PA followed by HDR brachytherapy.  After removal of fibrous tissue and mobilization of the tendons, 1 to 3 catheters per patient were placed intra-operatively.  Immediately after surgery, a planning computer tomography (CT) with 3D-planning was carried out.  Thereafter, 10 to 12 Gy were administered to 0 to 2 mm from the catheters' surface and the catheters were removed 6 to 12 hours after brachytherapy.  No complications were observed.  The mean contractures were reduced from 55.4° (standard error [SE] 19.6) to 15.4° (SE 6.7; p < 0.01); 1 patient showed progressive fibrosis of a non-treated ray during follow-up.  The authors concluded that HDR brachytherapy in combination with surgery was feasible and harbors the potential for combined modality therapy to reduce relapse rates of advanced or relapsing DC.  Moreover, these researchers stated that controlled studies are needed to examine the role of bi-modal therapy compared with PA alone.

Cryopreserved Placental Membrane

Dress and Tassis (2018) noted that DD is a rare connective tissue disorder resulting in progressive fibrosis and thickening of the palmar fascia, and contracture of the fingers due to excessive collagen deposition.  Staged surgical interventions are reserved for severe cases, yet worsening of fibrosis and contracture of fingers post-surgery, has been reported to have a recurrence rate as high as 85 %.

Dress and Tassis (2018) reported on the use of viable cryopreserved placental membrane (vCPM) allograft as an adjunct to open fasciectomy. In a patient with debilitating bilateral DD contractures of more than 20 years duration, this novel approach resulted in a 34.8 % ROM improvement and ability to fully extend all digits of the right hand.  No adverse events (AEs) were recorded.  At 1 year post-surgery, the patient had no decrease in ROM.  The authors concluded that these findings indicated that vCPM incorporation in open fasciectomy may provide benefit in reducing contracture recurrence in DD patients.  Moreover, they stated that long-term follow-up data are needed to provide additional insight on the utilization and clinical outcomes of vCPM in surgical fasciectomies.

Dynamic Manugraphy for Evaluation of the Outcome of Aponeurectomy in Patients with Dupuytren's Contracture

Garkisch and colleagues (2021) stated that DCs interfere with physiological gripping.  While limited aponeurectomy is an accepted treatment modality to restore finger mobility, methods to objectify functional outcome beyond determination of the ROM are scarce.  This study included patients with DC being scheduled for unilateral limited aponeurectomy.  Clinical data were gathered prospectively by chart review and interview.  The DASH-score and flexion contracture for fingers were registered before surgery, 3, and 6 months following surgery.  At the same time, dynamic manugraphy for simultaneous recording of the grip pattern and forces generated by the affected hand and anatomic areas (i.e., thumb, index finger, middle finger, ring finger, little finger and palm) were carried out.  All findings obtained during the follow-up period were compared to the situation at baseline.  Comparison between paired samples was performed using Wilcoxon rank test.  All p values were 2-sided and p < 0.05 was considered to be significant.  Out of 23 consecutively enrolled patients, 19 (15 men, 4 women) completed follow-up examinations.  Manugraphy confirmed the impairment of physiological gripping with concomitant pathological load distribution at base line.  Limited aponeurectomy significantly reduced flexion contractures; however, the DASH-score remained at an excellent level in 1 patient, indicated improvement in 11 and worsening in 7 patients; 6 patients had lower grip force at t6 compared to the pre-operative condition, although the pre-operative flexion contracture (greater than or equal to 110°) was considerably improved in all of them.  In 4 of those, the DASH-score improved while it turned worse in 2 of them.  The force of surgically treated fingers remained unchanged in t3 patients while it was improved and worsened in 50 % of the remaining patients, respectively.  Manugraphy revealed physiological gripping by enlargement of contact area and higher force transmission by the fingertips in 10 of 12 patients with constant or even improved DASH-score and in 3 of 7 patients with a worsened DASH-score.  The authors concluded that evaluating the reduction of flexion contracture and grip force alone was insufficient to comprehensively reflect the functional outcome of aponeurectomy for DC.  Visualizing physiological grip pattern provided an additional tool to objectify the success of surgical treatment.  These researchers stated that dynamic manugraphy is a promising tool to evaluate the outcome of limited aponeurectomy in patients with DC.

Hand Therapy After Collagenase Treatment

Aglen and colleagues (2019) stated that DC is a fibrotic hand condition in which 1 or more fingers develop progressive flexion deformities.  Quality of life (QOL) is diminished due to disabling limitations in performing everyday activities.  For DC patients treated with collagenase, referral for subsequent hand therapy is inconsistent.  It is unclear if subsequent hand therapy is beneficial compared to no therapy.  The purpose of this study is to examine if hand therapy improves DC patients' performance of and satisfaction with performing everyday activities 1 year after collagenase treatment.  These researchers will carry out a RCT with 2 treatment groups (hand therapy versus control) of DC patients who have received collagenase treatment.  DC patients with contracted MCP (hand therapy, n = 40; control, n = 40) and those with PIP involvement (hand therapy, n = 40; control, n = 40) comprise 2 subgroups, and these investigators will study if the treatment effect will be different between both groups (n = 160).  Patients with a previous injury or treatment for DC in the treatment finger are excluded.  Hand therapy includes edema and scar management, splinting, movement exercises, and practice of everyday activities.  The main outcome variable is patients' performance of and satisfaction with performing everyday activities, as assessed with the Canadian Occupational Performance Measure.  Secondary outcomes are DC-specific activity problems, as assessed with the Unité Rhumatologique des Affections de la Main scale, and active/passive flexion/extension of treated joints and grip force using standard measuring tools, and self-reported pain level.  Demographic and clinical variables, degree of scarring, cold hypersensitivity, number of occupational sick-leave days are collected.  Self-reported global impression of change will be used to assess patient satisfaction with change in hand function.  Assessments are performed pre-injection and 6 weeks, 4 months, and 1 year later.  Standard uni-variate and multi-variate statistical analyses will be used to evaluate group differences.  The authors concluded that this study aims to examine if hand therapy is beneficial for activity-related, biomechanical, and clinical outcomes in DC patients after collagenase treatment.  The results will provide an objective basis for determining whether hand therapy should be conducted after collagenase treatment.

Middle-Phalanx Excision and Ligament Reconstruction

Eiriksdottir and Atroshi (2019) stated that recurrent severe DC of the small finger's PIP joint is a difficult problem.  Further surgery carries high risk of complications and poor outcome.  Patients are often offered finger amputation.  These researchers have devised a novel surgical procedure consisting of middle phalanx mono-block resection and ligament reconstruction to create a new functioning inter-phalangeal joint.  Two patients requesting small-finger amputation because of severe PIP joint contracture after multiple treatments for DC were offered and accepted this new procedure.  Through a dorsal incision the extensor tendon was incised longitudinally exposing the middle phalanx and inter-phalangeal joints.  The collateral ligaments of both inter-phalangeal joints were detached from the middle phalanx.  The middle phalanx was dissected from soft tissues (including the flexor digitorum superficialis tendon) and removed.  The distal phalanx was brought proximally and the ends of the collateral ligaments were sutured with non-absorbable sutures with the joint held in full extension and congruency.  The 2 patients were evaluated at 18 months and 15 months after surgery, respectively.  Both patients regained good finger posture with almost full extension and had normal sensation and no pain.  Active flexion in the new inter-phalangeal joint was 60 degrees and 35 degrees, respectively.  Both patients had full MCP joint flexion and extension, normal 2-point discrimination in the small finger and higher grip strength in the treated than the contralateral hand.  Radiographs showed a congruent new inter-phalangeal joint.  Both patients were very satisfied with the outcome.  The authors concluded that in patients with DC and severe PIP joint contracture after multiple treatments, this novel procedure consisting of middle-phalanx excision and ligament reconstruction creating a new functioning inter-phalangeal joint had good short-term outcomes and is a favorable alternative to finger amputation.  Moreover, these researchers stated that longer follow-up will show whether these results are durable.  Furthermore, longer follow-up can show whether the patients develop symptomatic osteoarthritis (OA) in the new inter-phalangeal joint.

Night Orthosis

In a multi-center, open, randomized controlled trial, Jerosch-Herold et al (2011) evaluated the effect of night splinting on self-reported function, finger extension and satisfaction in patients undergoing fasciectomy or dermofasciectomy for Dupuytren's contracture.  A total of 154 patients from 5 regional hospitals were randomized after surgery to receive hand therapy only (n = 77) or hand therapy with night-splinting (n = 77).  Primary outcome was self-reported function using the DASH questionnaire.  Secondary outcomes were finger range of motion and patient satisfaction.  Primary analysis was by intention-to-treat.  A total of 148 (96 %) patients completed follow-up at 12 months.  No statistically significant differences were observed on the DASH questionnaire (0 to 100 scale: adjusted mean diff. 0.66, 95 % CI: - 2.79 to 4.11, p = 0.703), total extension deficit of operated digits (degrees: adjusted mean diff 5.11, 95 % CI: -2.33 to 12.55, p = 0.172) or patient satisfaction (0 to 10 numerical rating scale: adjusted mean diff -0.35, 95 % CI: -1.04 to 0.34, p = 0.315) at 1 year post surgery.  Similarly, in a secondary per protocol analysis no statistically significant differences were observed between the groups in any of the outcomes.  The authors concluded that no differences were observed in self-reported upper limb disability or active range of motion between a group of patients who were all routinely splinted after surgery and a group of patients receiving hand therapy and only splinted if and when contractures occurred.  Given the added expense of therapists' time, thermoplastic materials and the potential inconvenience to patients having to wear a device, the routine addition of night-time splinting for all patients after fasciectomy or dermofasciectomy is not recommended except where extension deficits re-occur.

In a pilot study, Kemler and colleagues (2012) evaluated the effectiveness of post-operative splinting after limited fasciectomy for Dupuytren's disease.  A total of 54 patients with a PIP joint flexion contractures of at least 30° were randomized to receive either a 3-month splinting protocol together with hand therapy under the direct supervision of hand therapists, or the same hand therapy alone.  Extension deficit of the PIP joint (primary outcome measure), global perceived effect, pain intensity, comfort and complications were assessed at baseline and 1 year after surgery.  In an intention-to-treat analysis, the group assigned to splint-plus-hand therapy had a mean reduction of 21° in flexion contracture after 1 year, compared with 29° in the group receiving hand therapy alone (p = 0.1).  There was no difference between the groups regarding other parameters.  After operative release of a Dupuytren's contracture, a post-operative protocol using a splint and hand therapy was no better than hand therapy alone in minimizing post-operative flexion contractures.

In a single-center RCT, Collis et al (2013) examined the effectiveness of night extension orthoses on finger range of motion and hand function for 3 months following surgical release of Dupuytren contracture.  These researchers also determined how well finger extension was maintained in the total sample.  They randomized 56 patients to receive a night extension orthosis plus hand therapy (n = 26) or hand therapy alone (n = 30).  The primary outcome was total active extension of the operated fingers (degrees).  Secondary outcomes were total active flexion of the operated fingers (degrees), active distal palmar crease (cm), grip strength (kg), and self-reported hand function using the Disabilities of the Arm, Shoulder, and Hand questionnaire (0 to 100 scale).  There were no statistically significant differences between the no-orthosis and orthosis groups for total active extension or for any of the secondary outcomes.  Between the first post-operative measure and 3 months after surgery, 62 % of little fingers had maintained or improved total active extension.  The authors concluded that the use of a night extension orthosis in combination with standard hand therapy has no greater effect on maintaining finger extension than hand therapy alone in the 3 months following surgical release of Dupuytren contracture.  These findings indicated that the practice of providing every patient with a night extension orthosis following surgical release of Dupuytren contracture may not be justified except for cases in which extension loss occurs after surgery.  They stated that their results also challenged clinicians to research ways of maintaining finger extension in a greater number of patients.

Samargandi and colleagues (2017) examined the role of night orthosis use after surgical correction of Dupuytren's contracture.  These investigators searched Medline, Embase, CINAHL, AMED, OTSeeker, and CENTRAL for articles published from inception of the databases to August 2015.  Assessment was undertaken by 2 independent reviewers.  Methodological quality of RCTs was assessed using the Cochrane risk of bias tool and the Newcastle-Ottawa instrument.  A total of 7 studies met the standard for inclusion in this review; 659 patients across these 7 studies were included in the analysis, with follow-up ranging from 3 to 72 months.  None of the included studies assessed recurrence.  The analysis revealed no significant improvement in range of motion (ROM) of hand joints for patients who received a static night orthosis after Dupuytren surgery compared with patients without an orthosis.  Similarly, no differences were found in patient-reported functional status across the 2 groups.  The authors concluded that the current literature does not appear to support the use of static night orthosis in addition to hand therapy after surgical correction of Dupuytren contracture.

Bowers et al (2021) stated that current prescribing information for the treatment of patients with DC with injectable CCH recommends use of a night extension orthosis for 4 months after treatment.  In a single-center study, these investigators examined if this treatment would improve the outcomes.  Adult patients with DC treated with CCH during the study period were eligible for inclusion.  Subjects were randomized to orthosis or no orthosis groups and were stratified based on the severity of contracture before randomization.  The orthosis group was fitted post-manipulation with a hand-based custom orthosis that held the treated finger in maximal comfortable extension, and subjects were instructed to wear the orthosis at night for 3 months.  They were assessed at 7 to 10 days, 30 days, and 90 days post-manipulation.  Orthosis compliance was measured with a survey.  The primary outcome measure was improvement in TAE, defined as the sum of active MCP, PIP, and DIP joint extension in the treated finger at 90 days after treatment.  Secondary outcomes included total active flexion (TAF), Michigan Hand Questionnaire scores, patient satisfaction, and clinical success.  A total of 26 patients completed the study, 12 in the orthosis group and 14 in the no orthosis group.  The majority of contractures (90 %) were primarily through the MCP joint.  Subjects in both groups showed significant improvements in TAE at 90-day follow-up (orthosis, p = 0.002; no orthosis, p = 0.001).  The difference in improvement in the median TAE between the 2 groups was not significant (p = 0.40).  There were no significant differences between groups for TAE, TAF, Michigan Hand Questionnaire scores, patient satisfaction, or clinical success at any of the time-points assessed (p > 0.05).  The authors concluded that in patients with DC with primarily MCP joint involvement, providing an orthosis after treatment with CCH may not offer a short-term benefit compared with CCH treatment alone in terms of TAE, TAF, or patient-reported outcome measures.  These researchers stated that future studies are needed to examine the role of night orthosis use in larger, more heterogenous populations at longer time-points; nevertheless, the findings of this study questioned the short-term benefit of night-time orthosis use following CCH treatment.  Level of Evidence = I.

Percutaneous Needle Aponeurotomy in Combination with Lipografting

Hovius and colleagues (2011) described a novel minimally invasive alternative for Dupuytren disease and its outcome.  The procedure consists of an extensive percutaneous aponeurotomy that completely disintegrates the cord and separates it from the dermis.  Subsequently, the resultant loosened structure is grafted with autologous lipo-aspirate.  After 1 week of post-operative extension splinting, patients are allowed normal hand use and are advised to use night splints for 3 to 6 months.  These investigators treated and reported on their experience with 91 patients (99 hands) operated on in Miami and Rotterdam; from 50 patients, the authors reported on goniometry (average follow-up of 44 weeks).  The contracture from the PIP joint improved significantly from 61 degrees to 27 degrees, and contracture from the MCP joint improved from 37 degrees to -5 degrees; 94 % of patients returned to normal use of the hand within 2 to 4 weeks and 95 % were very satisfied with the result.  No new scars were added, and a supple palmar fat pad was mostly restored.  Complications were digital nerve injury in 1 patient, post-operative wound infection in 1 patient, and complex regional pain syndrome in 4 patients.  The authors concluded that this new minimally invasive technique shortens recovery time, adds to the deficient subcutaneous fat, and leads to scarless supple skin.  By its ability to treat multiple rays, it addresses the abnormality in the entire hand.  The procedure is safe and effective, especially for primary cases.  Moreover, they stated that comparative prospective randomized studies are currently in process to fully determine the role of percutaneous aponeurotomy plus lipografting in the treatment of Dupuytren contracture.

Tuncel and colleagues (2017) described their experience with treating Dupuytren's disease using needle aponeurotomy and non-centrifuged autologous fat grafting.  The study included 17 patients (18 hands).  Patients were treated with needle aponeurotomy and non-centrifuged autologous fat graft under general anesthesia.  The fat grafts were injected into the surgical area so as to stay in contact with the operated site.  An extension splint was used for 1 week post-operatively and the patients received hand therapy for 3 weeks.  Before the treatment, the contracture in the PIP and MCP joints was a mean of 45.06 ± 13.44 degrees and 36.56 ± 13.09 degrees, respectively.  It was 1.61 ± 1.65 and -0.56 ± 3.78 degrees at 3 months, respectively.  The difference between these measurements was statistically significant.  The mean follow-up period was 12 months.  The results were satisfactory and no complications were observed during the follow-up period.  The authors concluded that based on the results of the study, percutaneous aponeurotomy with non-centrifuged autologous fat grafting was found to have significantly beneficial effects in the treatment of Dupuytren's disease.  These preliminary findings from a small (n = 17 subjects) study need to be validated by well-designed studies.

Radial Extracorporeal Shock Wave Therapy

Knobloch et al (2011) noted that Dupuytren's disease is a progressive disease due to unknown causal agents or genetics.  An epidemiological analysis of 566 cases in North Germany estimated that around 1.9 million Germans are suffering from Dupuytren's disease.  Beside Dupuytren's disease, there are a number of further less common forms of progressive fibromatosis, such as knuckle pads, plantar fibromatosis or Peyronie's disease.  Surgery in plantar fasciectomy yields to a 60 % recurrence rate depending on the extent of the plantar fasciectomy.  Peyronie's disease of the penis affects middle-aged men between 40 and 60 years with penile pain, curvature during erection and potential erectile dysfunction.  In a randomized controlled trial (RCT) in Peyronie's disease 2,000 focused extracorporeal shock waves reduced pain significantly and improved erectile function and quality of life.  These researchers hypothesize that focused extracorporeal shock wave therapy (ESWT) is able to reduce Dupuytren's contracture.  Given the fact that recurrence rate in Dupuytren's disease is high und unpredictable, ESWT as a non-invasive tool might be applicable both, in primary and secondary prevention of the progression as well as for treatment.  As such, these investigators have planned a RCT studying the effect of high-energy focused ESWT on patients suffering Dupuytren's disease with patient-related outcome measures such as the Disabilities of the Arm, Shoulder and Hand (DASH) score and the Michigan Hand Outcome Questionnaire as primary outcome parameters.

Brunelli and colleagues (2020) noted that while the effectiveness of focused ESWT in the treatment of DC is supported by 1 positive trial, the effects of radial ESWT is unclear.  This case-report described a 79-year old man with a 4-year history of impairment of left-hand function and pain due to DC with weakness and flexion deformities of middle and ring fingers.  He has not been treated before for this impairment.  The diagnosis of DC was based on clinical features and US images; treatment was 4 weekly sessions of radial ESWT with 1,400 impulses 3 bar each, 12-Hz.  The limitations in activities of daily living (ADL) were analyzed via the DASH and Michigan Hand Outcome Questionnaire (MHQ) at baseline, after 4 sessions of radial ESWT and at 4-months follow-up.  Data analysis showed a significant reduction of hand deformities and an improvement of ADL performance.  The effects continued at the 4-months follow-up.  The authors concluded that this case report demonstrated the feasibility of radial ESWT.  Radial ESWT sessions may be performed by a physiotherapist in outpatient clinics with cost reduction compared with surgical treatment and focused ESWT.  Radial ESWT is a non-invasive, well-tolerated therapy, so it should be considered in the treatment of DC.  Moreover, these researchers stated that further studies, including RCTs, are needed to examine the effectiveness of radial ESWT in DC and its comparable effects to focused ESWT.

Taheri et al (2022) examined the effect of shock wave therapy on the improvement of symptoms and function of patients with DC.  This research was a pre-post intervention study, carried out in patients referred to the physical medicine clinics of Isfahan during 2019 to 2020.  Subjects experienced shock wave therapy for 6 sessions, each in a week, and improvement of symptoms and function were assessed and compared after the period of study and follow-up (before treatment, 6 weeks after treatment, and 14 weeks after treatment).  The pain VAS and disabilities of the arm shoulder and hand questionnaire were completed for all patients at the mentioned time, and the finger contraction angle was also measured by a goniometer over these intervals.  A total of 20 patients, 11 (55 %) men and 9 (45 %) women participated in the study.  The mean and standard deviation (SD) of their age was 66.6 ± 7.11 years.  The trend of pain severity of patients was continuously and significantly decreasing up to 14 weeks, which implied the effectiveness of the intervention (p < 0.05).  Moreover, subjects' functional status improved due to the continuation of the intervention, and its trend was decreasing up to 14 weeks (p < 0.05).  As for the contraction angle, there was a continuous and significant decreasing trend until week 14, and the intervention was also effective on the contraction angle (p < 0.05).  The authors concluded that shock wave therapy could be effective in improving the symptoms and function of patients with DC.  Moreover, these researchers stated that more comprehensive studies with larger sample sizes and long-term follow-up are needed to ascertain the effects of shock wave therapy for the treatment of DC.

The authors stated that the non-referral of patients for follow-up was one of the limitations of this study, which could be solved by sufficient explanation to patients and appropriate and regular follow-up.  Another limitation of this study was the lack of funding, which it tried to overcome by reducing costs as much as possible.  Furthermore, these investigators tried to reduce the design costs, as much as possible, in order to collect the least sample size and to achieve proper internal and external validity.

Sorafenib for the Treatment of Dupuytren Disease

Schoenfeld et al (2022) noted that palmar and plantar fibromatosis are benign proliferative processes that present as a diffuse thickening or nodules of the hands and/or feet, and may lead to flexion contractures, pain, and functional impairment known as DC and Ledderhose disease, respectively.  Current treatments are non-curative and associated with significant morbidity.  In a case-series study, these investigators reported on the outcomes of 5 patients with advanced disease (non-surgical candidates) treated with sorafenib, which exhibited an expected safety profile.  All 5 patients reported objective responses as evaluated by a decrease in tumor size and/or tumor cellularity from baseline; and all 5 participants reported subjective pain relief and/or functional improvement.  Mechanistically, immunohistochemistry revealed patchy positivity for PDGFRβ, a known target of sorafenib.  The authors concluded that the outcomes of these 5 patients suggested the safety and effectiveness of a relatively well-tolerated oral agent in the treatment of DC and Ledderhose disease and suggested the need for future controlled studies.

Tension and Compression Orthoses

In a randomized study, Brauns and colleagues (2017) determined how much improvement 2 types of orthotic device (tension and compression) as only treatment intervention can provide on a Dupuytren's contracture.  Is a compression orthosis better than a tension orthosis?  A total of 30 patients with measurable flexion contractures of the fingers were identified.  Both primary and recurrence cases were included.  Patients were randomized in 2 groups of 15 patients: one group had a standard tension orthosis (Levame), and the other group a newly designed silicon compression orthotic device.  Patients were instructed to wear the orthotic devices 20 hours a day during 3-month study period.  Data were collected at 1st visit and after 3 months of orthotic treatment.  Primary outcomes were active extension deficit of each joint and total active extension (TAE) of the digit; secondary outcome was patient satisfaction.  Visual analog scale (VAS) score of function and esthetics (0 to 10 points) were recorded at the start and after 3 months.  Flexion contracture was reduced at least 5 degrees in all patients.  After 3 months, TAE was significantly reduced in both groups (both p < 0.001).  The mean change in TAE was 32.36° in the tension group and 46.47° in the compression group.  Although reduction of TAE deficit was bigger in the compression group, this difference was not statistically significant (p = 0.39); VAS scale of esthetics and functionality was significantly increased in both treatment groups.  The functional VAS scale after 3 months was 11 % higher in the compression group than in the tension group (p = 0.03).  A major complication of a tension orthotic is skin ulcers.  The authors concluded that tension and compression orthotic devices can be used as a non-operative treatment of Dupuytren's disease in both early proliferative untreated hands and aggressive post-surgery recurrence.  Moreover, they stated that although there is no statistically significant difference, compression orthoses appeared to be more effective and are better-tolerated; nevertheless, adjustment of orthotic design and research on long-term results are needed.

Ultrasound Guidance for Injection of Xiaflex

In a prospective, cohort study, Aguilella and colleagues (2022) compared the effectiveness of ultrasound (US)-guided injection of CCH in patients with DC, with the standard injection.  These researchers hypothesized that US-guided Injection of CCH is more effective than the standard injection.  These investigators treated consecutively 47 fingers with the standard injection and 43 with the US-guided injection.  Patients in both groups had the same inclusion criteria.  The degrees of contracture of the MCP and PIP joints were measured before treatment and after 3 months.  They compared the effectiveness of each type of injection with respect to obtaining a complete finger extension and to the percentage of improvement in each finger and in each joint.  With US-guided injection, complete finger extension was obtained in 54 % of cases and an 81 % mean percentage of correction of the finger contracture; with standard injection 49 % and 77 %, respectively.  In the MCP joint, the mean percentage of correction was 92.5 % in the US-guided Injection group and 84 % in the standard injection group.  In the PIP joint, it was 75.1 % in the US-guided injection group and 65.3 % in the standard injection group.  The authors concluded that these findings showed no statistical significance; these researchers stated that hand surgeons must balance the possible benefits of the US-guided injection with the complexity and resources needed to perform the technique.

Uterine Fibroids

Jayes and colleagues (2016) tested the hypothesis that a highly purified collagenase clostridium histolyticum will digest interstitial collagen in uterine fibroids and reduce their stiffness and evaluated the feasibility that clostridium histolyticum collagenase can be developed into an alternative treatment for fibroids. A secondary objective was to describe the collagen content of the fibroid tissue.  Fibroid tissue cubes (1-cm3; n = 154) were cut from 17 uterine fibroids that were obtained from 7 consented subjects undergoing scheduled hysterectomies.  Tissue cubes were injected with diluent, placebo, or highly purified collagenase clostridium histolyticum (0.05, 0.1, or 0.2 mg per cube) and incubated at 37°C for 24, 48, 72, or 96 hours.  At each time-point, 6 non-injected control cubes were also evaluated.  Tissue cubes were photographed before and after incubation.  Myometrial samples (n = 21) were also evaluated.  Stiffness was quantified through rheometry by measuring complex shear moduli of the tissues.  Percent fibrosis was determined by computerized analysis of Masson-Trichrome stained slides.  Digestion of collagen fibrils was confirmed by transmission electron microscopy.  Fibrosis in untreated fibroids ranged from 37 % to 77 % reflecting the collagen-rich nature of these tumors.  After treatment with collagenase for 96 hours, fibrosis ranged from 5.3 % to 2.4 %.  Transmission electron microscopy confirmed complete digestion of collagen fibrils.  Tissue stiffness was reduced with all 3 doses of collagenase treatment and at all 4 time-points.  Longer incubation times with collagenase caused greater reduction in stiffness and treated cubes lost their cuboidal shape and had gelatinous/liquefied centers.  At 96 hours stiffness in tissues treated with the lowest dose was reduced to 966 ± 106 Pascal compared to diluent-treated control at the same time (5,323 ± 903 Pascal; p < 0.0001; by analysis of variance with Tukey-Kramer).  The authors concluded that uterine fibroids have a high content of collagen that can be effectively digested by highly purified collagenase clostridium histolyticum resulting in reduced tissue stiffness.  Loss of stiffness may decrease bulk symptoms in-vivo and possibly lead to shrinkage of fibroids through changed mechano-transduction leading ultimately to reduced fibroid symptoms of pain and bleeding.  The authors stated that clinical trials are needed to evaluate safety and effectiveness of clostridium histolyticum collagenase including the rate of regrowth of fibroids.  They noted that the data of this study provided a strong rationale for using this purified collagenase in clinical trials as a local treatment for women with fibroids.


The above policy is based on the following references:

  1. Abe Y. Comparison of treatment outcomes after collagenase injection and percutaneous needle fasciotomy for Dupuytren's contracture: Objective and subjective comparisons with a 3-year follow-up. Plast Reconstr Surg. 2020;145(6):1464-1474.
  2. Aggarwal R, Blazar PE. Dupuytren's contracture. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed July 2018.
  3. Aggarwal R, Blazar PE. Dupuytren's contracture. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed June 2019.
  4. Aglen T, Matre KH, Lind C, et al. Hand therapy or not following collagenase treatment for Dupuytren's contracture? Protocol for a randomised controlled trial. BMC Musculoskelet Disord. 2019;20(1):387.
  5. Aguilella L, Perez-Giner R, Higueras-Guerrero V, et al. Can collagenase effectiveness in Dupuytren's contracture be improved by using ultrasound-guided injection? A comparative study. J Plast Surg Hand Surg. 2022;56(1):23-29.
  6. Atroshi I, Strandberg E, Lauritzson A, et al. Costs for collagenase injections compared with fasciectomy in the treatment of Dupuytren's contracture: A retrospective cohort study. BMJ Open. 2014;4(1):e004166.
  7. Auxilium Pharmaceuticals, Inc. Xiaflex (collagenase clostridium histolyticum). Prescribing Information. Malvern, PA; Auxilium; February, 2010. 
  8. Auxilium Pharmaceuticals, Inc. Xiaflex (collagenase clostridium histolyticum) for injection, for intralesional use. Prescribing Information. PL-0108-001.g. Malvern, PA; Auxilium; revised July 2015. 
  9. Azzopardi E, Boyce DE. Clostridium histolyticum collagenase in the treatment of Dupuytren's contracture. Br J Hosp Med (Lond). 2012;73(8):432-436.
  10. Badalamente MA, Hurst LC, Hentz VR. Collagen as a clinical target: Nonoperative treatment of Dupuytren's disease. J Hand Surg Am. 2002;27(5):788-798.
  11. Badalamente MA, Hurst LC. Enzyme injection as nonsurgical treatment of Dupuytren's disease. J Hand Surg Am. 2000;25(4):629-636.
  12. Ball C, Izadi D, Verjee LS, et al. Systematic review of non-surgical treatments for early dupuytren's disease. BMC Musculoskelet Disord. 2016;17(1):345.
  13. Betz N, Ott OJ, Adamietz B, et al. Radiotherapy in early-stage Dupuytren's contracture. Long-term results after 13 years. Strahlenther Onkol. 2010;186(2):82-90.
  14. Bowers NL, Merrell GA, Foster T, Kaplan FTD. Does use of a night extension orthosis improve outcomes? J Hand Surg Glob Online. 2021;3(5):272-277.
  15. Brauns A, Van Nuffel M, De Smet L, Degreef I. A clinical trial of tension and compression orthoses for Dupuytren contractures. J Hand Ther. 2017;30(3):253-261.
  16. Brazzelli M, Cruickshank M, Tassie E, et al. Collagenase clostridium histolyticum for the treatment of Dupuytren's contracture: Systematic review and economic evaluation. Health Technol Assess. 2015;19(90):1-202.
  17. Brunelli S, Bonanni C, raballesi M, Foti C. Radial extracorporeal shock wave therapy: A novel approach for the treatment of Dupuytren's contractures: A case report. Medicine (Baltimore). 2020;99(24):e20587.
  18. Chen NC, Shauver MJ, Chung KC. Cost-effectiveness of open partial fasciectomy, needle aponeurotomy, and collagenase injection for dupuytren contracture. J Hand Surg Am. 2011;36(11):1826-1834.
  19. Cheng HS, Hung LK, Tse WL, Ho PC. Needle aponeurotomy for Dupuytren's contracture. J Orthop Surg (Hong Kong). 2008;16(1):88-90.
  20. Ciernik IF, Goldschmidt P, Wosle M, Winter J. Feasibility of aponeurectomy in combination with perioperative 192 Ir high dose rate brachytherapy for Dupuytren's disease. Strahlenther Onkol. 2021;197(10):903-908.
  21. Collis J, Collocott S, Hing W, Kelly E. The effect of night extension orthoses following surgical release of Dupuytren contracture: A single-center, randomized, controlled trial. J Hand Surg Am. 2013;38(7):1285-1294.
  22. Corradino B, Di Lorenzo S, Moschella F. Treatment of stages III-IV of the Dupuytrens Disease using a personal approach: Percutaneous needle fasciotomy (PNF) and minimal invasive selective aponeurectomy. Acta Chir Plast. 2013;55(1):19-22.
  23. Dress CM, Tassis EK. A case of Dupuytren's disease managed with viable cryopreserved placental membrane adjunct to open palmar fasciectomy. J Surg Case Rep. 2018;2018(3):rjy055.
  24. Eiriksdottir A, Atroshi I. A new finger-preserving procedure as an alternative to amputation in recurrent severe Dupuytren contracture of the small finger. BMC Musculoskelet Disord. 2019;20(1):323.
  25. Endo Pharmaceuticals, Inc. Xiaflex (collagenase clostridium histolyticum) for injection, for intralesional use. Prescribing Information. Malvern, PA: Endo Pharmaceuticals, revised August 2022.
  26. Fitzpatrick AV, Moltaji S, Ramji M, Martin S. Systematic review comparing cost analyses of fasciectomy, needle aponeurotomy, and collagenase injection for treatment of Dupuytren's contracture: Une analyse de coûts systématique comparant la fasciectomie, l'aponévrotomie percutanée à l'aiguille et l'injection de collagénase pou traiter la maladie de Dupuytren. Plast Surg (Oakv). 2021;29(4):257-264.
  27. Foucher G, Medina J, Navarro R. Percutaneous needle aponeurotomy: Complications and results. J Hand Surg Br. 2003;28(5):427-431.
  28. Garkisch A, Mittlmeier T, Kalpen A, et al. Dynamic manugraphy as a promising tool to assess the outcome of limited aponeurectomy in patients with Dupuytren's contracture. Front Med (Lausanne). 2021;7:604891.
  29. Hirase T, Suresh R, Cotton MO. Percutaneous needle fasciotomy versus collagenase injection for Dupuytren's contracture: A systematic review of comparative studies. J Hand Microsurg. 2021;13(3):150-156.
  30. Hovius SE, Kan HJ, Smit X, et al. Extensive percutaneous aponeurotomy and lipografting: A new treatment for Dupuytren disease. Plast Reconstr Surg. 2011;128(1):221-228.
  31. Hurst LC, Badalamente MA, Hentz VR, et al. Injectable collagenase clostridium histolyticum for Dupuytren's contracture. N Engl J Med. 2009;361(10):968-979.
  32. Jayes FL, Liu B, Moutos FT, et al. Loss of stiffness in collagen-rich uterine fibroids after digestion with purified collagenase clostridium histolyticum. Am J Obstet Gynecol. 2016;215(5):596.e1-596.e8.
  33. Jerosch-Herold C, Shepstone L, Chojnowski AJ, et al. Night-time splinting after fasciectomy or dermo-fasciectomy for Dupuytren's contracture: A pragmatic, multi-centre, randomised controlled trial. BMC Musculoskelet Disord. 2011;12:136.
  34. Jordan GH. The use of intralesional clostridial collagenase injection therapy for Peyronie's disease: A prospective, single-center, non-placebo-controlled study. J Sex Med. 2008;5(1):180-187.
  35. Kadhum M, Smock E, Khan A, Fleming A. Radiotherapy in Dupuytren's disease: A systematic review of the evidence. J Hand Surg Eur Vol. 2017;42(7):689-692.
  36. Karabeg R, Jakirlic M, Arslanagic S, et al. Results of surgery treatment of Dupuytren's contracture in 115 patients. Med Arh. 2012;66(5):329-331.
  37. 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.
  38. Kemler MA, Houpt P, van der Horst CM. A pilot study assessing the effectiveness of postoperative splinting after limited fasciectomy for Dupuytren's disease. J Hand Surg Eur Vol. 2012;37(8):733-737.
  39. Knobloch K, Kuehn M, Vogt PM. Focused extracorporeal shockwave therapy in Dupuytren's disease -- a hypothesis. Med Hypotheses. 2011;76(5):635-637.
  40. Leafblad ND, Wagner E, Wanderman NR, et al. Outcomes and direct costs of needle aponeurotomy, collagenase injection, and fasciectomy in the treatment of Dupuytren contracture. J Hand Surg Am. 2019;44(11):919-927.
  41. Lellouche H. Dupuytren's contracture: Surgery is no longer necessary. Presse Med. 2008;37(12):1779-1781.
  42. Manet MP, Roulot E, Teyssedou JP, et al. Dupuytren's contracture: Needle aponeurotomy is an alternative to surgery. Rev Med Interne. 2011;32(4):241-248.
  43. Mella JR, Guo L, Hung V. Dupuytren's contracture: An evidence based review. Ann Plast Surg. 2018;81(6S Suppl 1):S97-S101.
  44. Nanchahal J, Ball C, Davidson D, et al. Anti-tumour necrosis factor therapy for Dupuytren's disease: A randomised dose response proof of concept phase 2a clinical trial. EBioMedicine. 2018;33:282-288.
  45. National Institute for Clinical Excellence (NICE). Needle fasciotomy for Dupuytren’s contracture. Interventional Procedure Guidance 43. London, UK: NICE; February 2004.
  46. National Institute for Health and Clinical Excellence (NICE). Radiation therapy for early Dupuytren's disease. Interventional Procedure Guidance (IPG) 573. London, UK: NICE; December 21, 2016. 
  47. National Institute for Health and Clinical Excellence (NICE). Radiation therapy for early Dupuytren’s disease. Interventional Procedure Guidance 368. London, UK: NICE; November 2010.
  48. Nehra A, Alterowitz R, Culkin DJ, et al. Peyronie’s Disease: AUA Guideline. J Urol. 2015;194(3):745-753. 
  49. Oxfordshire NHS Trust. Surgery for Dupuytren’s contracture. Interim Treatment Threshold Statement. Priorities Forum Policy Statement. Oxford, UK: NHS; October 15, 2009.
  50. Peimer CA, Blazar P, Coleman S, et al.  Dupuytren contracture recurrence following treatment with collagenase clostridium histolyticum (CORDLESS study): 3-year data. J Hand Surg Am. 2013;38(1):12-22.
  51. Samargandi OA, Alyouha S, Larouche P, et al. Night orthosis after surgical correction of Dupuytren contractures: A systematic review. J Hand Surg Am. 2017;42(10):839.e1-839.e10.
  52. Sanjuan Cervero R, Franco Ferrando N, Poquet Jornet J. Use of resources and costs associated with the treatment of Dupuytren's contracture at an orthopedics and traumatology surgery department in Denia (Spain): Collagenase clostridium hystolyticum versus subtotal fasciectomy. BMC Musculoskelet Disord. 2013;14:293.
  53. Scheibler AG, Marks M, Hensler S, et al. Factors predicting the 1-year outcome of collagenase treatment for Dupuytren's disease. Arch Orthop Trauma Surg. 2019;139(4):583-588.
  54. Scherman P, Jenmalm P, Dahlin LB. Three-year recurrence of Dupuytren's contracture after needle fasciotomy and collagenase injection: A two-centre randomized controlled trial. J Hand Surg Eur Vol. 2018;43(8):836-840.
  55. Schoenfeld JD, Agaram NP, Lefkowitz RA, et al. Sorafenib in Dupuytren and Ledderhose disease. Oncologist. 2022;27(3):e294-e296.
  56. Seegenschmiedt MH, Olschewski T, Guntrum F. Radiotherapy optimization in early-stage Dupuytren's contracture: First results of a randomized clinical study. Int J Radiat Oncol Biol Phys. 2001;49(3):785-798.
  57. Smeraglia F, Del Buono A, Maffulli N. Collagenase clostridium histolyticum in Dupuytren's contracture: A systematic review. Br Med Bull. 2016;118(1):149-158.
  58. Swartz WM, Lalonde DH. MOC-PS(SM) CME article: Dupuytren's disease. Plast Reconstr Surg. 2008;121(4 Suppl):1-10.
  59. Taheri P, Salek N, Mousavi M, Maghroori R. The effect of shock wave therapy on improving the symptoms and function of patients with Dupuytren's contracture. Adv Biomed Res. 2022;11:3.
  60. Therkelsen LH, Skov ST, Laursen M, Lange J. Percutaneous needle fasciotomy in Dupuytren contracture: A register-based, observational cohort study on complications in 3,331 treated fingers in 2,257 patients. Acta Orthop. 2020;91(3):326-330.
  61. Trojian TH, Chu SM. Dupuytren's disease: Diagnosis and treatment. Am Fam Physician. 2007;76(1):86-89.
  62. Tuncel U, Kurt A, Gumus M, et al. Preliminary results with non-centrifuged autologous fat graft and percutaneous aponeurotomy for treating Dupuytren's disease. Hand Surg Rehabil. 2017;36(5):350-354.
  63. U.S. Food and Drug Administration. FDA approves Xiaflex for debilitating hand condition. FDA News. Silver Spring, MD; FDA; February 2, 2010.
  64. Villegas MR, Baeza A, Usategui A, et al. Collagenase nanocapsules: An approach to fibrosis treatment. Acta Biomater. 2018;74:430-438.
  65. Wong CR, Huynh MNQ, Fageeh R, McRae MC. Outcomes of management of recurrent Dupuytren contracture: A systematic review and meta-analysis. Hand (N Y). 2021 Feb 22 [Online ahead of print].