Dupuytren's Disease: An Outcomes-Focused Update

Abstract

Dupuytren's disease (DD) remains a common fibroproliferative condition with significant sequelae and impact on patient's lives. The etiology of DD is poorly understood, and genetic predisposition is thought to be a strongly associated factor. Despite remarkable strides in improving our molecular understanding of DD, clinical treatment options have not yet overcome the frequently encountered challenge of recurrence. Recurrence rates continue to shape the prognosis of this fibrotic condition. In this outcomes-focused article, the various treatment modalities are reviewed. This further emphasizes the importance of patient education and providing them with the information to make informed decisions about their treatment.

Dupuytren's disease (DD) was named after the famous Parisian surgeon Guillaume Dupuytren who described in great detail this common fibroproliferative condition of the digito-palmar fascia. ^{1 2} DD leads to progressive tightening and shortening of this fascia along lines of mechanical tension, limiting digit extension. This localized fibrotic condition can lead to permanent Dupuytren's contractures which can ultimately result in loss of hand function. ³ The prevalence of DD increases with age with an estimated mean of 12, 21, and 29% at the ages of 55, 65, and 75, respectively. ⁴ Furthermore, DD is more prevalent among males with a family history of this fibrotic condition. ⁵ DD is strongly associated with northern European descent and appears to be significantly less prevalent among females, with a male-to-female ratio approaching 6:1 that normalizes and trends toward parity with increasing age. ^{6 7 8 9} Some studies estimate the contribution of genetic risk in DD to be 80% among Caucasian patients. ¹⁰ Population studies uncovered a correlation between allele frequencies of 26 known DD single-nucleotide polymorphisms and DD prevalence among various populations. ¹¹ These studies partially explain the significantly elevated prevalence of DD among individuals of North-Western European descent compared with individuals of African or East Asian descent.

The etiology of DD is poorly understood and is postulated to be associated with alcoholism, diabetes, epilepsy, antiepileptic medications, hypercholesterolemia, smoking, trauma, and manual work. However, it remains unclear if these conditions have a direct causative effect on the development of DD. ^{12 13 14} At a molecular level, oxygen radicals and aberrant upregulation of collagen synthesis are thought to be associated with the development of DD. ^{15 16 17} Myofibroblasts have been identified as the pathogenic cell type responsible for palmar fascia contractures experienced in DD. ^{18 19 20} It is widely observed that DD presents first as nodules and then progresses to fibrotic cords. ^{21 22}

Transforming growth factor (TGF)-β upregulation is central to the pathogenesis of DD. ²³ TGF-β is a pleiotropic cytokine that regulates a broad range of biological processes including extracellular matrix deposition and immune modulation. ^{24 25}

Currently available treatment options exhibit high recurrence rates post-intervention, in addition to potentially burdensome long rehabilitation periods. The recurrence rate of DD after needle fasciotomy, collagenase injection, or fasciectomy ranges between 21 and 84.9%. ²⁶

Relevant Anatomy and Common Classification Systems

DD affects the hand architecture in a fashion that leads to potential permanent flexion contractures across multiples joints ( Table 1 ). In addition to affecting the metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints of the fingers, DD can affect the thumb and first webspace. This is the third most common site of involvement after the ring and little fingers where the abductor digiti minimi can be frequently involved. ^{27 28 29} A plethora of classification systems have been described for DD. Luke's histopathological classification divided DD into three stages: proliferative, involutional, and residual, roughly corresponding to nodules, nodular cords, and non-nodular cords. ²²

Table 1. Relevant anatomy to Dupuytren's disease.

Diseased “Cords”	Constituent Normal “Bands”	Contracture
Pretendinous cord	Pretendinous band	MCP joint flexion
Central cord	Superficial digital fascia	PIP joint flexion
Spiral cord	Spiral band	PIP joint flexion
Lateral cord	Lateral digital fascia	PIP joint flexion
Retrovascular cord	Retrovascular band	PIP joint flexion
Natatory cord	Natatory ligament	Adduction

Abbreviations: MCP, metacarpophalangeal; PIP, proximal interphalangeal.

Another widely adopted grading system is the Tubiana staging ³⁰ ( Table 2 ). This clinical staging approach is based on the composite flexion contracture in the affected hand. The combined flexion contracture of the MCP and PIP joints of each ray is placed in groups of 45-degree increments.

Table 2. Tubiana staging for Dupuytren's disease.

Stage	Description
Stage 0	No contracture or lesion
Stage N	Palmar nodule without the presence of contracture
Stage 1	Total flexion deformity of 0 to 45 degrees
Stage 2	Total flexion deformity of 45 to 90 degrees
Stage 3	Total flexion deformity of 90 to 135 degrees
Stage 4	Total flexion deformity greater than 135 degrees

Dupuytren's Diathesis

Dupuytren's diathesis refers to the presence of certain patient or disease characteristics that may indicate a more aggressive form of DD. The term Dupuytren's diathesis was originally coined by Hueston. ³¹ Originally, this included: bilateral palmar disease, family history of DD, and ectopic disease. Typically, some conditions are associated with DD and the term “ectopic” encompasses the following: Ledderhose disease (plantar fibromatosis), ³² Garrod pads ³³ (knuckle pads over the dorsum of the PIP joints), and Peyronie disease (fibrotic disease-causing curvature of the penis). ³⁴ The current widely adopted definition of Dupuytren's diathesis also includes male gender in addition to bilateral disease presentation, family history, and an age of onset less than 50 years. ^{35 36}

It is important to note that DD also has multiple non-genetic associations reported in the literature. Recent studies indicate an association between DD and advanced age, male gender, family history of DD, adhesive capsulitis (frozen shoulder), and diabetes mellitus. ^{1 37} Additionally, a positive dose–response relationship was highlighted between DD and heavy alcohol consumption, smoking, and manual work exposure showed a positive dose–response relationship. ³⁸

Noninvasive Management Approaches

Significant strides were made in ameliorating the deleterious impact DD could have on patients' quality of life (QoL). However, controversy remains regarding outcomes, recurrence, and cost-effectiveness. Massaging the affected hand ³⁹ and splinting ⁴⁰ for early DD were reported, but most studies on these two approaches are not large enough for generalizable conclusions to be drawn. In addition, given the progressive nature of DD, it remains unlikely that such conservative measures would alone prevent or reverse flexion contractures. The general indications for intervention in DD are summarized in Table 3 . ⁴¹

Table 3. Indications for intervention in Dupuytren's disease.

Treatment indication	Comment
Any PIP joint contracture	More challenging rehabilitation (consider early intervention)
MCP joint contracture greater than 30 degrees	Good prognosis even with more severe contractures
Altered neurovascular function	Compression neuropathy
Positive Hueston's (tabletop) test	Positive if the patient is unable to place fingers flat on the table
Significant webspace contractures	Especially first webspace

Abbreviations: MCP, metacarpophalangeal; PIP, proximal interphalangeal.

Collagenase Injection

Since the Food and Drug Administration approval of collagenase clostridium histolyticum in 2010 for DD treatment, it has continued to gain popularity. ⁴² This minimally invasive approach presents a viable treatment option targeting the excessive collagen produced in DD. Two key randomized clinical trials heralded the wide adoption of this management approach: CORD I and CORD II. ^{43 44} These two landmark trials concluded that collagenase injection can be highly effective and well-tolerated by DD patients and can significantly reduce contractures and improve the range of motion in joints affected by advanced DD.

This treatment approach involves directly injecting 0.58 mg of collagenase into a tethering Dupuytren's cord in multiple aliquots. The injected enzyme was then given 24 hours to react with the diseased cord, weakening the injected areas to facilitate cord rupture by external manual passive extension. The outcomes of collagenase injection at the MCP joint are comparable to limited fasciectomy, but yielded inferior results in correcting PIP joint flexion contractures. ⁴⁵

Patients who had collagenase injections had a lower overall incidence of serious adverse events, which was comparable to limited fasciectomy patients. ⁴⁶ Some of the adverse events associated with collagenase injections included tendon injury, skin injury, and hematoma development. ⁴⁶ A recent retrospective study evaluating 199 fingers postcollagenase injection highlighted a high recurrence rate as a key drawback of this technique. This study concluded that patients' satisfaction and willingness to undergo collagenase injection treatment may be negatively correlated with perceived recurrence. ⁴⁷ In the CORDLESS study evaluating the long-term results of collagenase injections, Peimer et al concluded that 5 years after successful collagenase injection, the recurrence rates of MCP and PIP joints contractures were 47%, statistically similar to that of surgical treatment. ⁴⁸

A key advantage of collagenase injections, however, is the broad consensus of the safety of injecting multiple affected digits concurrently. Multiple simultaneous collagenase injections for Dupuytren's contracture had a similar safety profile and treatment efficacy when compared with single injections. ⁴⁹

Needle Aponeurotomy or Percutaneous Needle Fasciotomy

This approach involves utilizing a small-gauge hypodermic needle under local anesthesia to perform a controlled fasciotomy to release tethered cords. Needle aponeurotomy is suitable for the obviously palpable cord lying immediately deep to skin in a cooperative patient. ^{50 51} Overall, the correction of MCP joint flexion contractures appears superior in contrast to the PIP joint irrespective of the treatment modality. ^{52 53} Studies indicate needle aponeurotomy provided a successful correction to 5 degrees or less contracture immediately postprocedure in 98% (791) of MCP joints and 67% (350) of PIP joints. Despite the heterogeneity in outcome reporting with respect to disease recurrence following needle aponeurotomy, the recurrence rate has been reported between 48 and 65% in studies with a mean follow-up of 3 to 5 years. ⁵² A distinctive advantage of needle aponeurotomy is the increased cost-effectiveness of this approach when compared with open fasciectomy as these procedures may be performed in an outpatient clinic under local anesthesia. ⁵⁴ Key disadvantages of needle aponeurotomy include a steep learning curve and difficulty in correcting PIP flexion contractures, potentially related to their shortened collateral ligaments. ⁵⁵ However, needle aponeurotomy has a lower complication rate and quicker recovery when compared with open fasciectomy and therefore may be offered to patients as a first-line treatment. ⁵⁵

The role and impact of needle aponeurotomy and lipofilling has been recently investigated. Data suggest that, needle aponeurotomy and lipofilling provided less durable corrections compared with limited fasciectomy at 5-year follow-up in patients with primary DD, although the 35% higher rate may be lower than has previously been reported for traditional percutaneous needle fasciotomy. ⁵⁶

Open Fasciectomy

Open fasciectomy remains an option for Dupuytren's contracture and limited fasciectomy is one of the most common management options available to DD patients. ^{57 58} It involves the excision of the affected fascia through an open surgical incision. The known surgical risks include: injuries to the neurovascular bundle, skin necrosis, edema, and complex regional pain syndrome (CRPS), with joint stiffness and reduced digital flexion being among the most common complications. ⁵⁹

The open palm technique was originally described by McCash in 1964. The procedure involves performing transverse incisions within the skin creases, followed by open fasciotomy and extension splinting of the fingers during secondary healing of sizable palmar wounds. ⁶⁰ More recent techniques, including less invasive modifications to the McCash technique, have been developed to avoid the morbidity of the large wounds. ^{61 62} In fact, several methods of surgical wound closure have been proposed: the use of a Bruner incision or performing serial Z-plasties along the longitudinal incision lines are well-accepted methods to prevent linear scar contractures. ⁶¹ The recurrence rate comparing these two techniques is not statistically significantly different. ⁶³ Chen et al reported in a systematic review of the literature an overall complication rate of 14 to 67% with open partial fasciectomy, with the most common complications consisting of nerve injury, infection, and CRPS. ⁶⁴ Recent data indicates that fasciectomy may be safely and cost-effectively performed under local anesthesia without a hand tourniquet in a community hospital setting. ⁶⁵

Outcomes Data on Dupuytren's Disease

One of the key challenges in quantifying the outcomes of DD management is the lack of widely adopted and standardized indices to objectively compare the results of various treatment modalities. This heterogeneity in outcomes reporting renders the clinical results between studies noncomparable.

Data from a randomized clinical trial involving 115 affected hands from 111 patients suggest that the 5-year recurrence rate in the percutaneous needle aponeurotomy group was significantly greater (84.9%) than in the limited fasciectomy group (20.9%) ( p  < 0.001). ⁶⁶ Recurrence rates in this trial were defined as an increase in extension deficit greater or equal to 30 degrees compared with the results at 6 weeks.

Patients who received collagenase injection reported larger and quicker functional improvements as demonstrated by greater Michigan Hand Outcomes Questionnaire scores. ⁶⁷ Additionally, the collagenase injection group was more satisfied with their finger mobility and hand function. When comparing the degree of residual contracture between collagenase injection and limited fasciectomy, no statistically significant difference was found between these two methods at the MCP joint level. For the affected PIP joint, however, the outcome was worse in the collagenase injection group. ⁴⁵

Economic data indicate that limited fasciectomy is a cost-effective intervention for recurrent high-severity MCP joint contractures. However, needle aponeurotomy was found to be the only cost-effective intervention in recurrent low-severity MCP joint contractures and PIP joint contractures of all severity. Interestingly, collagenase injections were not determined to be a cost-effective intervention for recurrent Dupuytren's contracture in a study with a simulated cohort of 10,000 individuals. ⁶⁸ This may be attributed to the direct added cost of the collagenase injections and higher recurrence rates leading to a willingness-to-pay threshold of $100,000 per quality-adjusted life-year gained.

A key metric in evaluating outcomes in DD management is the risk of reoperation and recurrence. Recent level II evidence for 5-year recurrence (defined as a 30-degree increase in passive extension deficit) indicates that the combined recurrence of PIP and MCP joint contracture is 84.9, 32, and 21% for needle aponeurotomy, collagenase injection, and open fasciectomy, respectively. ⁶⁹

Conclusion

DD is a fibroproliferative condition of the palmar fascia that often leads to permanent debilitating hand contractures with a substantial deleterious impact on patients' QoL. ²⁶ Despite the expanding number of treatment options available to ameliorate the outcome of DD, it is important for patients to understand that the treatment options available are not curative and recurrence or new disease is common. Therefore, the hand surgeon plays an important role in educating patients, helping them set realistic expectations, and guiding them through informed discussions of the available treatment options.