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Corresponding author: Nicholas P. Iannuzzi, MD, Department of Orthopaedics & Sports Medicine, University of Washington, 4245 Roosevelt Way NE Box 354740, Seattle, WA 98105.
Dupuytren disease is a fibroproliferative disorder that affects the palmar fascia of the hand and results in varying degrees of nodule and cord formation. Over time, patients may develop progressive contractures, impairing their ability to type, to perform with fine instruments, or to participate in social activities such as shaking hands. Treatment options for Dupuytren contractures include needle aponeurotomy (NA), injection of collagenase Clostridium histolyticum (CCH) with manipulation of the digits, and surgical fasciectomy. Over the past decade, the use of CCH has increased. Recent studies have provided additional data regarding the pathophysiology, indications, outcomes, and costs associated with the treatment for Dupuytren contractures, and this review highlights these advances.
Dupuytren disease was initially described in 1614 by Plater, who errantly ascribed the contractures to the flexor tendons. In the 18th century, a British surgeon, Henry Cline Sr, dissected a hand afflicted with the disease and noted that the abnormal tissue was superficial to the tendons.
Dupuytren subsequently published on the topic in the Lancet in 1834 and described a disease of the palmar aponeurosis distinct from an otherwise normal tendon structure.
He additionally reported the first description of an open palm technique, in which a palmar cord was severed through a transverse incision, allowing correction of the flexion deformity. The incision was left open, and orthosis fabrication was used to maintain correction.
Despite surgeons’ long familiarity with Dupuytren disease, the genetics of the condition remain incompletely understood. Dupuytren disease is heritable, following an autosomal dominant pattern with variable penetrance.
Genes associated with Dupuytren disease have been localized to an area of interest on chromosome 16q, and changes in this locus may lead to a pathologic downregulation of natural collagen breakdown and, thus, abnormal development of abundant collagen in the dermis.
The nodules and cords in Dupuytren disease are predominantly comprised of type III collagen, distinct from the normal type I collagen of the palmar fascia.
The cords themselves are relatively acellular, although increased cellularity is suggestive of more active and aggressive disease with a propensity for recurrence.
Dupuytren contractures develop in the presence of myofibroblasts: distinct cells which share contractile features of smooth muscle and collagen-producing fibroblasts.
Local signaling also plays a role in the development and progression of Dupuytren disease. Tumor growth factor beta directs myofibroblast migration and local factors, such as platelet-derived growth factor, epidermal growth factor, interleukin 1, tenascin, and periostin, affect cellular growth and activity.
Physicians’ understanding of the cellular biology and regulation of collagen in Dupuytren disease is rapidly increasing; however, an exhaustive discussion of these developments is beyond the scope of this review.
Clinical Presentation
A recent population survey demonstrated that up to 7% of the US population experiences clinical symptoms or carries the diagnosis of Dupuytren disease.
Patients are predominantly male and typically in their fifth decade or later. A family history of hand contractures is common, although not universal, and presentation may vary. Asymptomatic patients may present with Dupuytren nodules during a visit for unrelated issues, whereas patients with more advanced disease may present with severe contractures and functional limitations. Patients should be asked about the presence of concurrent fibromatoses, including fibrosis of the plantar fascia (Ledderhose disease) and fibrosis of the corpus cavernosum of the penis (Peyronie disease) and should be examined for dorsal hand fibrosis (Garrod pads).
Certain patients may present with a constellation of clinical factors constituting Dupuytren diathesis, initially described in 1963 by Hueston.
Patients presenting with Dupuytren diathesis were noted to experience more severe and rapidly progressive contractures and to have an increased risk of recurrence following intervention. More recently, the factors associated with the diathesis have been refined to include male sex, age of onset <50 years, bilateral disease, Garrod pads, and Northern European descent. With all factors present, a 3-fold increase in recurrence can be expected following treatment of contractures.
In clinical practice, the presence and severity of Dupuytren disease is typically communicated by delineating the joints and digits involved, the amount of contracture present at each joint, and the predominant cords that are present. Recent studies have evaluated the contributions of various cords to digital contractures. Pretendinous cords are estimated to contribute to greater than 80% of metacarpophalangeal (MCP) joint contracture and 44% of proximal interphalangeal (PIP) contracture (Fig. 1A, B), whereas retrovascular cords and the spiral cord may contribute to 23% and 20% of PIP contractures, respectively (Fig. 2).
The accessory collateral ligament may also contribute an additional 14% to PIP joint contractures; the accessory collateral ligament can be sectioned at the time of limited fasciectomy (LF) if indicated.
The natural history of Dupuytren disease is one of gradual progression over time, although progression is by no means universal and the time course can vary substantially between patients. A population study from Iceland demonstrated that of the 20% of the population evaluated with evidence of Dupuytren disease, only one-third went on to require intervention at 18 years.
Patients presenting with contracted cords were more likely to progress and warrant more aggressive monitoring and discussion of intervention. No preventative treatment has been shown to disrupt the process of progression of contracture.
Among the proposed preventative treatment options, radiotherapy warrants discussion. Particularly in Europe, radiotherapy has been used to try to prevent the progression of contracture in early Dupuytren disease. In a recent systematic review, Kadhum et al
identified 5 retrospective cohort studies and 1 randomized controlled trial that assessed the efficacy of radiotherapy. Although the most common dose of radiation among the studies was 30 Gy, doses ranged from 21 Gy to 42 Gy, with varying fractionation schedules. Among the studies, approximately 3.1%–10% of patients underwent surgery due to progression of Dupuytren disease following radiation; however, none of the studies included an untreated control group, making these results difficult to interpret. In addition, acute complications were noted in 20%–40% of patients, with late radiation-related changes in <10% of patients. Kadhum et al
concluded that radiotherapy should be considered an unproven treatment for early Dupuytren disease.
Although there is no universal agreement on treatment threshold, the consensus from published studies is that contractures of greater than 30° at the MP and 15° at the PIP merit discussion of intervention.
The degree of contracture is often monitored with the tabletop test, in which patients assess their own ability to lay their hand flat on a table. When the patient is no longer able to lay the hand flat, the degree of contracture present may merit intervention. Ultimately, the decision to treat Dupuytren contractures should be tailored to the individual patient. Specific functional limitations and goals should be discussed in conjunction with the potential risks of treatment. In elderly, more medically compromised patients, office procedures such as NA or CCH may improve function while limiting the potential for anesthesia-related complications. In contrast, younger patients, in whom anesthesia may pose fewer risks, may benefit from more aggressive interventions associated with lower rates of disease recurrence. Given enough time, recurrence of Dupuytren contractures may occur, and the provider should consider how initial treatment may have an impact on subsequent interventions.
Treatment
The current treatment options for Dupuytren disease are, in some ways, similar to those used in the 1800s, with the exception of collagenase, which has had a marked impact on modern disease management. The most common methods currently used to treat Dupuytren contractures include NA, collagenase injection, and LF. These options may be used for cords throughout the hand, and the decision to use one treatment method in lieu of others should be based on a combination of factors, including the degree of contracture, the specific joints involved, the likelihood of recurrence, and the potential for complications, as well as the provider’s experience with the procedure and ability to perform it successfully.
Needle Aponeurotomy
Generally performed in an office setting, NA uses a needle to perforate the cord repeatedly while maintaining gentle tension on the cord (Fig. 3).
Following transection of the cord, the digit can be passively extended to achieve correction (Fig. 4A, B). Although variations in technique exist, avoidance of a digital block has been described to facilitate patient feedback if the digital nerve is encroached upon during the procedure.
Needle aponeurotomy has been used for cords involving both the MCP and PIP joints, although the risk of neurovascular injury is higher when addressing central and spiral cords for PIP correction.
reported the results of NA in over 1,000 digits, including 807 MP joints and 522 PIP joints with average contractures of 35° and 50°, respectively. Following NA, 98% of MP joints and 67% of PIP joints were corrected to an extension deficit of 5° or less.
also noted that 85% of patients experienced recurrence of their contracture at 5 years, representing a 3-fold greater recurrence rate compared to LF.
Complications of NA are common and include skin tear, damage to flexor tendons, and injury to neurovascular structures. Incidences of skin tear may range from 3% to 16%.
Efficacy and safety of collagenase Clostridium histolyticum in the treatment of proximal interphalangeal joints in Dupuytren contracture: combined analysis of 4 phase 3 clinical trials.
In the office, collagenase may be injected along a diseased cord, often under local anesthetic. Manual extension of the digit is performed at a second visit 24 hours to 7 days later in order to rupture the cord. The initial FDA protocol avoided use of an anesthetic at the manipulation visit. Subsequent literature has demonstrated improved correction with use of an anesthetic, and this has become the current standard of care.
The effect of a therapy protocol for increasing correction of severely contracted proximal interphalangeal joints caused by Dupuytren disease and treated with collagenase injection.
Collagenase treatment of Dupuytren's contracture using a modified injection method: a prospective cohort study of skin tears in 164 hands, including short-term outcome.
FDA approval was initially limited to 0.58 mg in a single digit, with additional injections separated by 4 weeks. Subsequently, a second injection was approved such that 2 vials of 0.58 mg can be given at once to treat 2 digits simultaneously.
Each vial of CCH contains more than the FDA-approved dose of 0.58 mg. A recent study demonstrated that practitioners may administer the full content of the vial, as much as 0.8 mg per vial or a total of 1.6 mg for multiple digits, in a single visit without a significant increase in severe complications.
Collagenase treatment of Dupuytren's contracture using a modified injection method: a prospective cohort study of skin tears in 164 hands, including short-term outcome.
Recent studies have also demonstrated the safety and efficacy of CCH when used to treat retrovascular cords, cords involving the thumb and first webspace, and recurrent disease.
Dupuytren contracture recurrence following treatment with collagenase Clostridium histolyticum (CORDLESS [Collagenase Option for Reduction of Dupuytren Long-Term Evaluation of Safety Study]):5-year data.
Rates of initial correction following collagenase are similar to those following NA. Results from a combination of studies including 1,568 MCP joints and 1,081 PIP joints demonstrated improvement of contracture to 5° or less in 1,069 (68%) and 392 (36%) joints, respectively.
Dupuytren contracture recurrence following treatment with collagenase Clostridium histolyticum (CORDLESS [Collagenase Option for Reduction of Dupuytren Long-Term Evaluation of Safety Study]):5-year data.
Five years after treatment with CCH, recurrence of the contracture of 20° or greater was noted in 47% of joints that were initially corrected to 5° or less, including 39% of MCP joints and 66% of PIP joints.
evaluated the effectiveness of CCH in recurrent Dupuytren contractures. Their study included 31 MCP joints and 20 PIP joints with recurrent flexion contractures of 40° and 46°, respectively. Correction to 5° or less was accomplished in 65% of MCP joints and 45% of PIP joints after patients received up to 3 injections of CCH.
Complications following collagenase are common, affecting over 80% of patients.
Contusion and edema can be seen in greater than 75% of patients (Fig. 5). Lymphadenopathy is reported in up to 37% of patients and skin tear in 25%–41%.
Collagenase treatment of Dupuytren's contracture using a modified injection method: a prospective cohort study of skin tears in 164 hands, including short-term outcome.
Efficacy and safety of collagenase Clostridium histolyticum in the treatment of proximal interphalangeal joints in Dupuytren contracture: combined analysis of 4 phase 3 clinical trials.
Although the rates of these complications are quite high, the rate of serious complication, such as tendon or pulley rupture and neurovascular injury, is substantially less than 1%.
Studies of patient-reported outcome measures (PROMs) suggest that greater than 85% of patients are satisfied following collagenase treatment for Dupuytren disease.
Collagenase Clostridium histolyticum in patients with Dupuytren's contracture: results from POINT X, an open-label study of clinical and patient-reported outcomes.
Limited fasciectomy is generally performed in the operating room and involves removal of diseased tissue over a discrete area or digit in order to correct a contracture. Radical fasciectomy refers to an extensive dissection of the hand with resection of the entirety of the palmar aponeurosis, whereas dermatofasciectomy refers to the resection of aponeurotic tissue and overlying skin over a discrete area for correction of contracture. Following dermatofasciectomy, tissue can be replaced with a skin graft from elsewhere to act as a “firebreak” or be left open to heal secondarily. Use of a “firebreak” has not been shown to decrease recurrence, and higher rates of complications have been reported with both radical fasciectomy and dermatofasciectomy compared to LF.
performed a prospective study and compared results after LF in 125 joints and NA in 167 joints. The authors noted correction of flexion contractures to 5° or less in 94% of MCP joints and 47% of PIP joints treated with LF compared to 55% of MCP joints and 26% of PIP joints treated with NA. When compared with CCH, LF has also demonstrated favorable early results, particularly at the PIP joint, with 6-week results demonstrating average contractures of 15° after LF compared with 25° after CCH.
Collagenase Clostridium histolyticum versus limited fasciectomy for Dupuytren's contracture: outcomes from a multicenter propensity score matched study.
(Table 1). Although LF is effective, the decision to proceed with fasciectomy should be weighed against the recovery time, the risk of complications, and the potential need for subsequent treatments in the event of recurrence. The risk of damage to neurovascular structures with repeat fasciectomy is estimated to be 10 times that of initial treatment, and Dupuytren himself proclaimed that “surgery is always a last resort.”
Regardless, open surgical treatment remains the gold standard for severe contracture, especially for severe PIP contracture and for patients who are interested in the most durable long-term correction.
Cost comparisons focusing on short-term results have compared the costs of CCH treatment with those of LF. These studies demonstrated a higher cost associated with LF, despite the high medication costs associated with CCH.
performed a cost analysis incorporating quality of life-years gained, and demonstrated that NA was cost-effective when the success rate neared 100% or was performed in an outpatient setting. The authors noted that collagenase was cost-effective when the cost of the medication is less than $945, whereas open LF was not cost-effective.
recently published an analysis that calls into question these conclusions. In their study, the authors incorporated costs associated with the treatment of recurrent disease within 5 years after initial treatment. Leafblad et al
demonstrated that collagenase had the highest rate of reintervention at 2 years and, thus, the highest cumulative costs over 5 years, whereas NA demonstrated the lowest overall cost and LF remained less expensive than CCH.
Comparison Studies
Compared to the larger body of literature surrounding Dupuytren disease, there are a relatively small number of high-quality comparison studies, and many of these studies have been published in recent years (Table 2). These randomized trials have demonstrated decreased rates of recurrent contracture following LF compared to NA. In addition to the van Rijssen et al
compared percutaneous NA and lipofilling to LF. At the 5-year follow-up, the authors found that patients treated with percutaneous NA and lipofilling (74%) had significantly higher rates of recurrence than patients treated with LF (39%; P = .002). Following LF, fat grafting has not been found to improve outcomes. Sambuy et al
compared LF with and without fat grafting and found that fat grafting was associated with lower outcomes scores and higher complication rates at 1 year, without improvement in the total passive extension deficit. An additional study by Kemler et al
Injectable collagenase versus percutaneous needle fasciotomy for Dupuytren contracture in proximal interphalangeal joints: a randomized controlled trial.
Comparison of treatment outcome after collagenase and needle fasciotomy for Dupuytren contracture: a randomized, single-blinded, clinical trial with a 1-year follow-up.
One-year results of needle fasciotomy and collagenase injection in treatment of Dupuytren's contracture: a two-centre prospective randomized clinical trial.
2-year follow-up Primary: Reduction in contracture by ≥50%
Clinical improvement maintained in 8% (2/24) of CCH patients and 32% (6/19) of PNA patients (P < .05). More, transient, complications in CCH group (93% vs 24%)
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.
Prospective, randomized trial, >30° TPED in a single ray
CCH (36 patients) vs PNA (34 patients)
3-year follow-up Primary: Recurrence, defined as an increase in TPED of ≥20° compared to results at day 30 after treatment
Recurrence at MCP joint in 26% (8/31) of CCH patients and 29% (9/31) of PNA patients, recurrence at PIP joint in 53% (8/15) of CCH patients and 60% (9/15) of PNA patients
PNA (167 joints) v. LF (125 joints)Postoperative extension orthosis fabrication and hand therapy (28 patients) vs hand therapy without orthosis fabrication (26 patients)
TPED at 1 year after surgery
TPED 21° in orthosis plus therapy group, 29° in therapy alone group. Not significantly different
Collagenase manipulation after CCH injection at day 1 vs day 7
Prospective randomized trial, TPED ≥20° MCP joint or PIP joint
Manipulation 1 day after injection (22 patients) vs 7 days after injection (24 patients)
TPED 30 days after manipulation, pain and skin tear at manipulation
No difference in TPED for MCP joint or PIP joint manipulated on day 1 or day 7. No difference in pain or frequency of skin tear
DIP, distal interphalangeal; MCP, metacarpophalangeal; PALF, percutaneous aponeurotomy and lipofilling; PNA, percutaneous needle aponeurotomy; TPED, total passive extension deficit; URAM, Unité Rhumatologique des Affections de la Main; VAS, visual analog scale.
Randomized trials comparing the effectiveness of collagenase to percutaneous needle aponeurotomy have demonstrated mixed results. One study performed by Skov et al
Injectable collagenase versus percutaneous needle fasciotomy for Dupuytren contracture in proximal interphalangeal joints: a randomized controlled trial.
found a higher rate of complications (93% vs 24%, respectively) and a lower rate of maintained clinical improvement (8% vs 32%, respectively) at 2 years in the PIP joints of patients treated with CCH and percutaneous needle aponeurotomy. Further studies evaluating both MCP and PIP joints or MCP joints alone demonstrated no significant differences in the improvement of contractures or the rates of recurrence between 1 and 3 years after treatment.
Comparison of treatment outcome after collagenase and needle fasciotomy for Dupuytren contracture: a randomized, single-blinded, clinical trial with a 1-year follow-up.
One-year results of needle fasciotomy and collagenase injection in treatment of Dupuytren's contracture: a two-centre prospective randomized clinical trial.
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.
The use of a local anesthetic before collagenase administration and the timing of manipulation after collagenase administration have also been the subject of recent controlled trials. Nordenskjöld et al
demonstrated decreased pain associated with the injection of a local anesthetic and the subsequent injection of collagenase when compared with the injection of collagenase alone. Mickelson et al
demonstrated no difference in the total passive extension deficit, pain, or the frequency of skin tears in patients who were manipulated 1 or 7 days after administration of collagenase.
Limitations of the Current Literature
Despite recent, higher-quality studies, a direct comparison of results between treatment options remains difficult. Werker et al
has noted varying definitions of success in studies currently published. Clearance of disease, improved mobility at 5 years, full flexion and extension, and the percentage of improvement in extension have been reported in the literature.
The use of PROMs also remains uncommon in studies evaluating Dupuytren disease, and often these PROMs do not adequately assess outcomes for Dupuytren disease.
The most commonly used PROMs in Dupuytren disease studies are the Disabilities of the Arm, Shoulder, and Hand and Quick-Disabilities of the Arm, Shoulder, and Hand scores; however, these scores have been noted to be limited by ceiling effects and may have poor overall validity with respect to Dupuytren disease.
In order to address these limitations, the Unité Rhumatologique des Affections de la Main scale was developed, which asks a series of 9 questions (Table 3) and scores each answer based on difficulty from 0 (no difficulty) to 5. Although this score has been validated among a series of patients treated for Dupuytren disease, the scoring system has seen limited use in the literature, and questions remain regarding its wider applicability.
Despite surgeons’ long familiarity with Dupuytren disease, many questions surrounding the condition remain unanswered. Further study is required to fully understand the genetic and environmental risk factors associated with Dupuytren disease. In addition, more rigorous studies using commonly accepted definitions of success are needed to better compare treatment results. Moving forward, the adoption of validated and generalizable PROMs may improve surgeons’ understanding of the impact Dupuytren disease has upon patients. In recent years, the treatment of Dupuytren disease has been markedly altered by the advent of CCH, and patients and providers have gravitated toward this office-based approach. In select patients and in the hands of experienced providers, NA remains an effective treatment for Dupuytren contractures, although there remains a population for whom surgical treatment will remain the gold standard.
Efficacy and safety of collagenase Clostridium histolyticum in the treatment of proximal interphalangeal joints in Dupuytren contracture: combined analysis of 4 phase 3 clinical trials.
The effect of a therapy protocol for increasing correction of severely contracted proximal interphalangeal joints caused by Dupuytren disease and treated with collagenase injection.
Collagenase treatment of Dupuytren's contracture using a modified injection method: a prospective cohort study of skin tears in 164 hands, including short-term outcome.
Dupuytren contracture recurrence following treatment with collagenase Clostridium histolyticum (CORDLESS [Collagenase Option for Reduction of Dupuytren Long-Term Evaluation of Safety Study]):5-year data.
Collagenase Clostridium histolyticum in patients with Dupuytren's contracture: results from POINT X, an open-label study of clinical and patient-reported outcomes.
Collagenase Clostridium histolyticum versus limited fasciectomy for Dupuytren's contracture: outcomes from a multicenter propensity score matched study.
Injectable collagenase versus percutaneous needle fasciotomy for Dupuytren contracture in proximal interphalangeal joints: a randomized controlled trial.
Comparison of treatment outcome after collagenase and needle fasciotomy for Dupuytren contracture: a randomized, single-blinded, clinical trial with a 1-year follow-up.
One-year results of needle fasciotomy and collagenase injection in treatment of Dupuytren's contracture: a two-centre prospective randomized clinical trial.
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.
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