Are you confident of the diagnosis?

Dupuytren’s disease (DD) is a chronic and often progressive fibromatosis of the palmar fascia that can lead to debilitating flexural contracture of the digit about the metacarpophalangeal (MCP) or proximal interphalangleal (PIP) joints. The ring finger is the most likely to be involved, followed by the fifth and middle fingers. The thumb and index fingers are rarely affected. Bilateral hand involvement is seen in 45% of cases.

• What you should be alert for in the history

Patients are most often white men over 50 years of age who present with decreased range of motion and/or loss of dexterity in the affected digit. Although extension is limited, finger flexion is often preserved. The inability to reach into a pocket or don a pair of gloves may lead to the initial presentation. Once established, the condition is usually painless.

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History should include a time course for disease progression, which generally advances through three sequential stages:

  • A thickened nodule or band in the palmar aponeurosis

  • A pretendinous band limiting extension of the affected digit

  • Permanent flexure contraction

Characteristic findings on physical examination

Further physical examination findings include blanching of overlying skin upon active extension of the digit and textural abnormalities, such as furrowing and pitting, which are created by tethering of the dermis to underlying fascia via the Grapow fibers.

Precise goniometric measurement should be performed to aid in eventual disposition. MCP contracture should be measured with the PIP passively extended, while PIP contracture should be measured with the MCP held in flexion. A positive Hueston tabletop sign, indicating that the patient is unable to lay his or her palm flat on a table, can aid in the diagnosis as it is typically associated with approximately 30 degrees of flexure contraction.

Ledderhose’s disease is a progressive fibromatosis, similar to DD, that affects the plantar fascia. Ambulation becomes increasingly difficult with progressive firbromatosis and stiffening of the toes. Likewise, Peyronie’s disease is a progressive fibrosing condition that affects the tunica albuginea of the penis. It is felt that both of these conditions share genetic and pathophysiologic similarities with DD, and an improved understanding of either condition may further elucidate the true etiology of DD.

Diagnosis confirmation

The diagnosis of DD is usually obvious. In its earliest stage, DD may resemble a callus. It can be easily differentiated from trigger finger, camptodactyly (fixed flexion of interphalangeal joint), diabetic cheiroarthropathy, and tendinous injury causing flexion contracture, as these conditions all lack firm, painless nodules at onset. Inflammation and pain with passive range of motion may indicate concomitant tenosynovitis. Ganglion cysts of the flexor tendon sheath present as small, firm, tender nodules at the MCP flexion crease, whereas Dupuytren’s contracture is usually less well circumscribed and presents at the distal palmar crease.

The differential diagnosis expands when history or examination findings do not correlate with the aforementioned clinical stages, or lesions occur outside of the normal patient demographic in populations such as children or young adults. In such instances, giant cell tumor of the tendon sheath, soft tissue sarcoma, and enchondroma must be added to the differential diagnosis. The best initial step in evaluating atypical presentations is three-view radiography of the affected hand.

Expected results of diagnostic studies

Histologically, DD is marked by a proliferation of myofibroblasts. Disease course generally mirrors the connective tissue repair seen in active wound healing. A histologic staging system describing three progressive stages of disease was first proposed by Luck in 1959:

  • Proliferative stage: Randomly arranged collagen fibrils surrounded by proliferating fibroblast

  • Involution stage: Myofibroblasts are the predominant cell type and collagen fibrils organize along lines of tension.

  • Residual stage: Hypocellular fibrotic stage with uniformly oriented collagen bundles.

These progressive stages have since been confirmed with the use of Herovici stain, which differentiates type III and type I collagen. As DD progresses, the proportion of type III collagen decreases. Lam et al have proposed an alternative histologic staging system in which stage I disease is characterized by a type III to I collagen ratio of greater than 35%, stage II 20% to 35%, and stage III less than 20%.

There are no routine serologic or genetic tests recommended to make the diagnosis of DD. Ultrasound may facilitate the identification of landmarks for therapeutic injection, but imaging studies are not generally required for diagnosis when the presentation is classic. Other imaging should be reserved for atypical presentations, as above.

Who is at Risk for Developing this Disease?

There is likely a genetic predisposition to the development of DD. The sibling recurrence-risk ratio is 2.9. An autosomal dominant pattern of inheritance with incomplete penetrance is the most widely accepted mode of transmission. However, no single genetic alteration has proven to be causative, and routine genetic analysis is not considered standard practice.

White males of northern European descent are at the greatest risk of developing of DD. The prevalence rate among Norwegians over 60 years of age is approximately 30%, whereas only sporadic cases have been reported in Hispanics, Indians, Native Americans, and Africans. To date, the largest epidemiologic study in the United States has estimated an overall prevalence rate of 3.4%.

A recent systematic review estimated the worldwide male to female ratio to be 5.9 to 1, which has been attributed to the sharp increase in prevalence seen in men greater than 45 years of age. However, by the 9th decade of life, it appears the incidence equalizes between men and women.

Several risk factors for the development of DD have been proposed, but few are consistently supported in the literature. A prospective study found alcohol and tobacco consumption to be independent risk factors for the development of DD. However, chronic liver disease apart from alcoholism does not appear to confer an increased risk. Diabetes mellitus is also a risk factor for the development of DD (odds ratio of 1.75), with the highest rates seen among insulin-dependent diabetics followed by those on the oral antihyperglycemic agents metformin and sulfonylureas. Conversely, 5% of all DD patients are diabetics.

Epilepsy, and perhaps more directly chronic anticonvulsant therapy, was at one time felt to be unequivocally linked to the development of DD, but more recent studies have called this association into question. When DD occurs in epileptics, it is more likely to be bilateral, symmetric, and associated with other fibrotic conditions such as knuckle pads and plantar fibromatosis. There is also conflicting data regarding an association with trauma, manual labor, HIV, and hypercholesterolemia. Rheumatoid arthritis is the only condition reported to have a lower prevalence of DD compared with the general population.

What is the Cause of the Disease?

• Etiology

DD is a fascial fibroproliferative disorder of uncertain etiology, although a genetic origin has been suggested. DD has been associated with single nucleotide polymorphisms in the gene encoding Zf9, a TGF-β1 transcription factor. Heteroplasmic mutations within the mitochondrial 16s ribosomal RNA region have also been implicated. Antibodies to types I – VI collagen, which are thought to play a role in the pathogenesis of DD by some, are more prevalent with certain HLA-DR alleles, suggesting a possible inherited immunologic susceptibility. More recently, a study of 2325 patients from the Netherlands, Germany, and the United Kingdom found that 6 of 9 loci associated with DD contained genes encoding proteins involved in the Wnt-signaling pathway. Again, no simple monogenic mendelian inheritance pattern has been delineated, and routine genetic testing is not recommended.

• Pathophysiology

Approximately 50 associated molecular abnormalities essential to the wound healing process have been reported in the literature, to include altered expression or activity of various cytokines (TGF-β, PDGF, etc), extracellular matrix proteins (β catenin, fibronectin, etc), and matrix metalloproteinases. The relative contribution of each alteration to disease pathogenesis remains unknown at this time.

Finally, oxidative stress and damage related to free radical generation have been proposed as an alternate mechanism for DD formation. Support for this hypothesis stems from increased tissue hypoxanthine levels seen in DD and the documented associations with diabetes, chronic alcohol consumption, and smoking.

Systemic Implications and Complications

Dupuytren’s contracture is seen in conjunction with other fibroproliferative conditions such as knuckle pads (44% to 54%), plantar fibromatosis (aka Ledderhose’s disease, 6% to 31%), and penile fibromatosis (aka Peyronie’s disease, 2% to 8%). Such ectopic fibrous proliferations are commonly seen with Dupuytren’s diathesis, which is characterized by severe, bilateral hand involvement in young white men with a strong family history of DD. This constellation of findings is reportedly associated with more severe and progressive disease as is radical side involvement

Fasting blood glucose levels are warranted if other elements in the history and physical are concerning for diabetes mellitus. Otherwise, no routine workup is indicated for DD.

Treatment Options

Surgical approach

  • Open fasciotomy

  • Percutaneous needle aponeurotomy (fasciotomy)

  • Fasciectomy

  • Dermofasciectomy

  • Amputation

Non-surgical approach

  • Observation

  • Clostridium histolyticum collagenase injection

  • Intralesional corticosteroids

  • Radiotherapy

  • Intralesional interferon-gamma

  • Ilomastat

  • 5-Fluorouracil

Optimal Therapeutic Approach for this Disease

After the diagnosis of DD has been established and prognostic factors such as Dupuytren’s diathesis have been considered, a severity assessment must be performed to direct the treatment approach.

Patients with mild disease may benefit from non-invasive interventions. Anecdotally, early nodules may respond well to modifications that reduce trauma or strain on the effected palm such as padding or wide grips. Nighttime splinting and soft tissue manipulation may improve symptoms, but data is limited.

Surgical intervention is the current mainstay of treatment in more severe or progressive cases. Referral to a hand surgeon is appropriate. There is no universally accepted indication for surgical intervention, but a positive tabletop test, 30 to 40 degree flexion contracture at the MCP, any degree of contracture at the PIP, and functionally limiting or symptomatic disease have been proposed. A 2010 systematic review found no evidence to support one surgical technique over the others, but did find an increased recurrence rate following needle fasciotomy. A randomized control trial of 111 patients comparing percutaneous needle fasciotomy to limited fasciectomy found a higher rate of recurrence in the needle fasciotomy group after 5 years, and these recurrences occurred sooner than those post-fasciectomy. A 2015 Cochrane review found insufficient evidence to suggest superiority of any single surgical intervention.

A full discussion of all surgical techniques and their indications is beyond the scope of this chapter, and referral to a hand surgeon is recommended once the decision has been made to pursue surgical correction.

Generally speaking, indications for non-surgical intervention are similar to those for surgical treatment (ie, functional impairment or disease progression). C histolyticum collagenase was approved by the FDA as an injectable treatment for DD in 2010. In a phase III study of 308 patients with at least 20 degrees of MCP or PIP contracture who received up to three 0.58mg injections of C histolyticum collagenase at monthly intervals, contracture was reduced to less than 5 degrees in 64% [Collagenase Option for Reduction of Dupuytren’s (CORD) I]. The treatment was more efficacious when flexion was less than 50 degrees at the MCP or less than 40 degrees at the PIP.

There was no evidence of recurrence in collagenase-treated individuals at 90-day follow-up in CORD I. However, 3-year follow-up data of 1,080 C histolyticum collagenase treated patients did show recurrence in 35% of treated joints (MCP 27%; PIP 56%), which is comparable to recurrence rates with standard surgical approaches. While treatment-related local reactions such as edema, pain and bruising occur in a majority of patients with collagenase injection, serious adverse events are rare and include tendon rupture and complex regional pain syndrome. Concurrent injection of 2 affected joints on the same hand may be associated with increased local side effects to include skin laceration, but the overall risk of serious adverse effects does not seem to be increased. Unfortunately, there are no prospective studies comparing collagenase injection to traditional surgical approaches at this time.

The evidence for other non-surgical interventions is not as robust. Intralesional triamcinolone injections of 40mg/mL have led to subjective improvement in nodules and symptoms for some patients, but overall the efficacy is limited and side effects such as atrophy are common. Radiotherapy with orthovoltage has been shown to halt the long-term progression of DD if applied early, when the flexion deformity is less than 5 degrees. Intralesional 5-fluorouracil, the broad spectrum matrix metalloproteinase inhibitor Ilomastat, and intralesional interferon injections remain primarily experimental at this time and their use should be restricted.

Patient Management

Most surgeons advocate for post-surgery physical therapy and splinting, although the evidence in support of splinting has recently been questioned. A 2015 Cochrane review concluded that splinting may not improve post-operative outcomes, with the caveat that evidence reviewed was deemed low-quality.

Recurrence rates following surgical correction vary widely based on disease severity, the involved joint, and surgical technique (0% to 71%). Definitions of recurrence are not well defined, so there is little agreement in the literature with regard to recurrence rates for various surgical techniques. Any estimate of recurrence or complication rates should be deferred to the consulting hand surgeon. Generally speaking, surgical correction of the PIP joint requires more aggressive techniques with higher likelihood of recurrence when compared with MCP correction.

The long-term recurrence risk with collagenase injection appears similar to traditional surgical interventions, however less long-term data is available following collagenase injection. As mentioned above, the risk of serious adverse events with collagenase therapy is low, but 97% of patients experience at least one minor side effect during injection or the subsequent manipulation required to release the fibrous cord.

Unusual Clinical Scenarios to Consider in Patient Management

Keep in mind that most patients with DD never require surgery and can be managed expectantly.

Individuals with Dupuytren’s diathesis (symmetric, bilateral disease of early onset in young white men with evidence of ectopic fibroplasia on examination) may experience more severe and rapidly progressive disease. For these individuals a more aggressive approach should be considered early in the disease course in an attempt to prevent debilitation.

What is the Evidence?

Hart, MC, Hooper, G. “Clinical associations of Dupuytren’s disease”. Postgrad Med J. vol. 81. 2005. pp. 425-8. (This review weighs the evidence in support of or against the many proposed clinical associations with Dupuytren's disease. Associations reviewed include alcohol use, epilepsy, trauma, diabetes mellitus, rheumatoid arthritis, gout, and human immunodeficiency virus infection. The article also reviews clinical features of disease and pathogenesis.)

Wheeless, CR. “Wheeless' textbook of orthopedics: Dupuytren's contracture. Duke Orthopaedics”. (A free online text book maintained by the Department of Orthopaedics at Duke University, this resource provides easily accessible clinical summaries of most orthopaedic conditions. The chapter on Dupuytren's contracture provides a concise summary on clinical findings.)

Griffin, LY. “Essentials of musculoskeletal care”. 2005. (Essentials of Musculoskeletal Care is a reference book that provides detailed summaries of most orthopaedic conditions and offers differential diagnoses by location and other clinical characteristics. Contains tables comparing entities within the differential diagnosis of DD and discusses the initial workup of each condition listed.)

Trojian, TH, Chu, SM. “Dupuytren’s disease: diagnosis and treatment”. Am Fam Physician. vol. 76. 2007. pp. 86-9. (This article is a primary care review of DD. It contains pictorial representations of the progressive stages of DD and reviews strength of evidence for the various associated primary care conditions.

Fitzgerald, AM, Kirkpatrick, JJ, Naylor, IL. “Dupuytren’s disease: the way forward?”. J Hand Surg Br. vol. 24. 1999. pp. 395-9. (This article considers the evidence in favor of DD as a modification of wound healing, rather than the previously accepted position that DD represents a neoplastic process. It discusses molecular biology and histologic evidence in support of a wound-healing theory.)

Bisson, MA, McGrouther, DA, Nudera, V, Grobbelaar, AO. “The different characteristics of Dupuytren’s disease fibroblasts derived from either nodule or cord: expression of alpha-smooth muscle actin and the response to stimulation by TGF-beta1”. J Hand Surg Br. vol. 28. 2003. pp. 351-6. (This article details basic science research in support of a wound-healing hypothesis for DD. The authors demonstrated TGF-beta1 inducible myofibroblast populations within tissue from Dupuytren's nodes and cords ex vivo, and they comment on the potential clinical significance of these findings.)

Luck, JV. ” Dupuytren's contracture; a new concept of the pathogenesis correlated with surgical management”. J Bone Joint Surg Am. vol. 41. 1959. pp. 635-64. (Included for historical reference, this is the initial description of a three-phase histologic progression in Dupuytren's contracture.)

Lam, WL, Rawlins, JM, Karoo, RO, Naylor, I, Sharpe, DT. ” Re-visiting Luck's classification: a histological analysis of Dupuytren's disease”. J Hand Surg Eur. vol. 35. 2010. pp. 312-7. (The authors stained histologic specimens from patients with DD with a Herovici stain to demonstrate the decreasing proportion of collagen III as the condition progresses. This article also introduces a new histologic staging system based on the ratio of type III to type I collagen.)

Hindocha, S, John, S, Stanley, JK, Watson, SJ, Bayat, A. ” The heritability of Dupuytren's disease: familial aggregation and its clinical significance”. J Hand Surg Am. vol. 31. 2006. pp. 204-10. (The researchers conclude that familial clustering in DD is most likely due to genetic influence rather than shared environmental influences. The sibling recurrence-risk ratio for DD was calculated by interviewing and surveying family members of 92 index cases.)

Burge, P. ” Genetics of Dupuytren's disease”. Hand Clin. vol. 15. 1999. pp. 63-71. (This review discusses the wide variation in prevalence rates of DD among different populations. The author concludes that most pedigrees are consistent with an autosomal dominant mode of transmission, but also acknowledges that spontaneous cases are common and several complicating factors prohibit a true understanding of the genetics of DD.)

Yost, J, Winters, T, Fett, HC. ” Dupuytren's contracture. A statistical study”. J Hand Surg Am. vol. 90. 1955. pp. 568-72. (This is the largest epidemiologic study of DD in the United States. The paper outlines a cross sectional study of 5062 hospital inpatients in New York and calculates the overall prevalence to be 3.4%. The inherent weakness in the study design is a lack of generalizability.)

Hindocha, S, McGrouther, DA, Bayat, A. “Epidemiological evaluation of Dupuytren's disease; Incidence and prevalence rates in relation to etiology”. HAND. vol. 4. 2009. pp. 256-69. (The authors systematically review the 49 epidemiology articles in the literature pertaining to DD. They provide a table summarizing all 49 studies to include study design, geographical location, means of data collection, patient demographics, and risk factors of the population. The authors then select several studies that demonstrate how these factors may explain the wide variation in published prevalence rates.)

Godtfredsen, NS, Lucht, H, Prescott, E, Sorensen, TI, Gronbaek, M. ” A prospective study linked both alcohol and tobacco to Dupuytren's disease”. J Clin Epidemiol. vol. 57. 2004. pp. 858-63. (A prospective study using a 7254-patient cohort in Denmark that found alcohol and tobacco to be independent risk factors for the development of DD. Confounding factors such as age, sex, education level, and diabetes were controlled for. This is the strongest evidence in the literature to associate a comorbidity with the presence of DD.)

Attali, P, Ink, O, Pelletier, G, Vernier, C, Jean, F. “Dupuytren's contracture, alcohol consumption, and chronic liver disease”. Arch Intern Med. vol. 147. 1987. pp. 1065-7. (This is a prospective study undertaken to assess the prevalence of Dupuytren's disease in patients with alcoholic and non-alcoholic liver disease as well as alcoholics without evidence of liver disease. The study concluded that alcoholism, not liver disease, correlates with the formation of Dupuytren's disease.)

Geoghegan, JM, Forbes, J, Clark, DI, Smith, C, Hubbard, R. “Dupuytren's disease risk factors”. J Hand Surg Br. vol. 29. 2004. pp. 423-6. (This large case-control study was designed to assess the relative contributions of diabetes and epilepsy as risk factors for the formation of DD. The authors concluded that diabetes, not epilepsy, was a significant risk factor for DD. The inherent weakness of this study, as with any case-control study, is its inability to prove causality or calculate prevalence.)

Critchley, EM, Vakil, SD, Hayward, HW, Owen, VM. ” Dupuytren's disease in epilepsy: result of prolonged administration of anticonvulsants”. J Neurol Neurosurg Psychiatry. vol. 39. 1976. pp. 498-503. (This cross sectional study of 361 patients with chronic epilepsy on anticonvulsant therapy found a prevalence rate of 57% for DD. There was no difference in the prevalence of DD by subtype of epilepsy, thus leading the authors to conclude that chronic anticonvulsant therapy is the most likely explanation for the increased rates of DD in the epileptic population.)

Arafa, M, Steingold, RF, Noble, J. “The incidence of Dupuytren's disease in patients with rheumatoid arthritis”. J Hand Surg. vol. 9. 1984. pp. 165-6. (The first and only study to identify a comorbid condition that may be protective against the formation of DD. Patients with rheumatoid arthritis were found to have a lower incidence of DD compared with an age- and gender-matched control group.)

Bayat, A, Watson, JS, Stanley, JK, Ferguson, MV, Ollier, WE. “Genetic susceptibility to Dupuytren disease: association of zf9 transcription factor gene”. Plast Reconstr Surg. vol. 111. 2003. pp. 134-41. (This is a case control study assessing differences in single nucleotide polymporphisms in the zf9 gene between patients with DD and controls. The zf9 gene encodes a transcription factor that increases TGF-beta 1 expression in tissue. Zf9 was the first gene to be implicated in the pathogenesis of DD.)

Bayat, A, Walter, J, Lambe, H, Watson, JS, Stanley, JK. “Identification of a novel mitochondrial mutation in Dupuytren's disease using multiplex DHPLC”. Plast Reconstr Surg. vol. 115. 2005. pp. 134-41. (The authors discovered a previously unknown mutation located within the mitochondrial 16s rRNA region in 90% of Dupuytren's patients with a maternal inheritance pattern. This mutation was absent in all controls. While the significance of this finding remains unknown, it may one day provide further insight regarding the pathogenesis of DD as defective mitochondria disrupt apoptosis and generate oxidative stress.)

Pereira, RS, Black, CM, Turner, SM, Spencer, JD. ” Antibodies to collagen types I-VI in Dupuytren's contracture”. J Hand Surg Br. vol. 11. 1986. pp. 58-60. (Serum from patients with DD was more likely to contain autoantibodies against human collagen than serum from a control group in this small study. Specifically, there was a statistically significant increase in antibody to denatured type II collagen in patients with DD. Patients with this particular antibody were also more likely to have the HLA-DR4 allele, suggesting a possible inherited immunologic susceptibility.)

Brown, JJ, Ollier, W, Thomson, W, Bayat, A. “Positive association of HLA-DRB1*15 with Dupuytren's disease in Caucasians”. Tissue Antigens. vol. 72. 2008. pp. 166-70. (This cross sectional study found increased rates of HLA-DRB1*15 in patients with Dupuytren's disease (37.3%) compared with controls (20.9%). The mechanism by which this particular phenotype of HLA-DRB1 may contribute to the pathogenesis of Dupuytren's disease remains unknown at this time.)

Shih, B, Bayat, A. “Scientific understanding and clinical management of Dupuytren disease”. Nat Rev Rheumatol. vol. 6. 2010. pp. 715-25. (This is a comprehensive and up-to-date review of the molecular aberrations purposed to play a role in the pathogenesis of DD. This review also contains an evidence-based algorithm for the approach to patients with DD.)

Murrell, GA, Francis, MJ, Bromley, L. “Free radicals and Dupuytren's contracture”. Br Med J (Clin Res Ed). vol. 295. 1987. pp. 1373-5. (A small study that found six-fold higher levels of hypoxanthine in the palmar fascia of patients with DD when compared with control subjects. The authors hypothesize that the free radicals generated through the metabolism of this intermediate by xanthine oxidase lead to local ischemia and DD.)

Townley, WA, Baker, R, Sheppard, N, Grobbelaar, AO. “Dupuytren's contracture unfolded”. Br Med J. vol. 332. 2006. pp. 397-400. (A concise review of DD with an emphasis on clinical aspects and management. The authors define Dupuytren's diathesis and discuss the presentation of this constellation.)

Au-Yong, IT, Wildin, CJ, Dias, JJ, Page, RE. “A review of common practice in Dupuytren surgery”. Tech Hand Up Extrem Surg. vol. 9. 2005. pp. 178-87. (This article contains a compilation of questionnaire responses from 141 hand surgeons regarding their surgical management of patients with Dupuytren's disease. There was considerable variation in practice among the participating surgeons that was not explained by the experience level of the surgeons or their training background. The authors discuss the questionnaire responses in the context of the current body of literature.)

Brandt, KE. “An evidence-based approach to Dupuytren's contracture”. Plast Reconstr Surg. vol. 126. 2010. pp. 2210-4. (This article reviews the operative and non-operative treatment of DD. Evidence is weighed using the American Society of Plastic Surgeons Evidence Rating Scales. The author concludes that there is no convincing evidence to suggest superiority of one surgical approach over others.)

Becker, GW, Davis, TRC. “The outcome of surgical treatments for primary Dupuytren's disease – a systematic review”. J Hand Surg Eur Vol. vol. 35. 2010. pp. 623-5. (A systematic review that evaluates the recurrence and complication rates for individual surgical procedures used in the correction of Dupuytren's contracture. The authors noted wide disparity in definitions used among the studies. They did not find one surgical technique to be superior to others, but did note a higher recurrence rate with needle fasciotomy as compared to other techniques.)

Hurst, LC, Badalamente, MA, Hentz, VR, Hotchkiss, RN, Kaplan, TD. “Injectable collagenase clostridium histolyticum for Dupuytren's contracture”. N Engl J Med. vol. 361. 2009. pp. 968-79. (A prospective, randomized, double-blind, placebo-controlled, multicenter trial assessing the efficacy of injectable collagenase in patients with DD of the MCP and PIP joints. This was the phase III study that led the FDA to approve collagenase C histolyticum for the treatment of Dupuytren's contracture.)

Watt, AJ, Curtin, CM, Hentz, VR. ” Collagenase injection as nonsurgical treatment of Dupuytren's disease: 8-year follow-up”. J Hand Surg Am. vol. 35. 2010. pp. 534e1-9e1. (This is an 8-year follow-up study from a phase II trial of collagenase C histolyticum, which initially saw reduction of contracture to less than 5 degrees in 72 of 80 patients treated. Of the eight patients (6 MCP, 2 PIP) included in this follow-up study, six had experienced recurrence. Of the four who recurred in the MCP group, all were less severe than their initial presentation and overall patient satisfaction was high.)

Ketchum, LD, Donahue, TK. “The injection of nodules of Dupuytren's disease with triamcinolone acetonide”. J Hand Surg Am. vol. 25. 2000. pp. 1157-62. (Sixty-three patients with Dupuytren's contracture were treated with an average of 3.2 injections of intralesional triamcinolone leading to some degree of improvement in 97% of patients in this small, uncontrolled study. The outcomes were subjective, and half experienced reactivation of nodules 1 to 3 years following the last injection.)

Rayan, GM. ” Nonoperative treatment of Dupuytren's disease”. J Hand Surg Am. vol. 33. 2008. pp. 1208-10. (The author reviews the evidence for and against non-operative treatment modalities in the management of DD. Despite a lack of high-level clinical studies supporting many of the non-operative treatments, they are still in use today.)

Betz, N, Ott, OJ, Adamietz, B, Sauer, R, Fietkau, R, Keilholz, L. “Radiotherapy in early-stage Dupuytren's contracture. Long-term results after 13 years”. Strahlenther Onkol. vol. 186. 2010. pp. 82-90. (A controlled, prospective study in which 135 patients who received local radiotherapy for the treatment of DD were followed for a mean of 13 years. The authors found radiotherapy to be effective in preventing disease progression and improving symptomology. These benefits were greatest for early stage disease.)

Larson, D, Jerosch-Herold, C. “Clinical effectiveness of post-operative splinting after surgical release of Dupuytren's contracture: a systematic review”. BMC Musculoskelet Disord. vol. 9. 2008. pp. 104(Post-surgical splinting after correction of Dupuytren's contracture is widely advocated. However, as this review identifies, there is little level 1 evidence to support the most commonly used post-surgical splinting techniques as they relate specifically to Dupuytren's contracture.)

Larocerie-Salgado, J, Davidson, J. ” Nonoperative treatment of PIPJ flexion contractures associated with Dupuytren’s disease”. J Hand Surg Eur Vol. vol. 37. 2012. pp. 722-7. (Single-center case series of 13 patients demonstrating improvement in active proximal interphalangeal joint extension over the course of 12 months using nighttime static extension splinting and soft tissue mobilization techniques. Authors conclude that such interventions appear to delay or possibly even prevent need for invasive intervention).

Rodrigues, JN, Becker, GW, Ball, C, Zhang, W, Giele, H, Hobby, J, Pratt, AL, Davis, T. ” Surgery for Dupuytren’s contracture of the fingers”. Cochrane Database Syst Rev. vol. 12. 2015 Dec 9. pp. CD010143(Systematic review of 14 arcles describing 13 studies on surgical intervention for Dupuytren’s contracture. The author’s concluded that there is insufficient evidence to show superiority for needle fasciotomy vs fasciectomy, or interposition firebreak skin grafting vs z-plasty closure of fasiectomy. They also concluded that low-quality evidence suggests postoperative splinting may not improve outcomes and may actually impair outcomes by reducing active flexion.)

Coleman, S, Gilpin, d, Kaplan, TD, Houston, A, Kaufman, G. “Efficacy and safety of concurrent collagenase clostridium histolyticum injections for multiple dupuytren contractures”. J Hand Surg Am. vol. 39. 2014. pp. 57-64. (Multicenter open-label phase IIIb study of 60 patients receiving two 0.58mg collagenase injections in the same hand during one visit. Author’s acknowledge an increased incidence of local adverse effects (pruritus, lymphadenopathy, blood blister, skin laceration) versus single joint injection, however conclude that two joints can by co-injected effectively and safely.)

Peimer, CA, Blazar, P, Coleman, S, Kaplan, TD, Smith, T. “Dupuytren contracture recurrence following treatment with collagenase clostridium histolyticum (CORDLESS Study): 3-year data”. J Hand Surg. vol. 38A. 2013. pp. 12-22. (Three year follow-up data from 5-year non-treatment follow-up study of patients previously receiving collagenase clostridium histolyticum injections for dupuytren’s contracture of the hand. Of 1,080 collagenase treated joints, 35% experienced recurrence at 3 years, with recurrence more likely at the PIP than MCP joint. Authors report an absence of long-term safety concerns).

Van Rijssen, AL, ter Linden, H, Werker, PM. ” Fiver-year results of a randomized clinical trial on treatment in Dupuytren’s disease: percutaneous needle fasciotomy versus limited fascietomy”. Plast Reconstr Surg. vol. 129. 2012. pp. 469-77. (Prospective, randomized controlled trial with 5 year follow-up data showed increased recurrence rates for needle fasciotomy versus limited fasciectomy, with recurrence also occurring sooner post-treatment in the needle fasciotomy group. Older age at time of treatment decreased recurrence rates, thus the authors concluded that needle fasciotomy is preferred in elderly patients and for those willing to accept a possible early recurrence.)

Dolmans, GH, Werker, PM, Hennies, HC, Furniss, D, Festen, EA. “Wnt signaling and dupuytren’s disease”. N Engl J Med. vol. 365. 2011. pp. 307-17. (Analysis from 2325 patients with Dupuytren’s disease across three countries compared with 11562 controls revealed an association between Dupuytren’s and 11 SNPs from 9 different gene loci. Six of these nine loci coded proteins known to be involved in the Wnt-signaling pathway. The authors discuss the Wnt signaling pathway and purpose that aberrations in this pathway may result in Dupuytren’s contracture.)