eMedicine Specialties > Dermatology > Benign Neoplasms

Dupuytren Contracture

Author: Felisa S Lewis, MD, Resident Physician, National Capital Consortium Dermatology Program, Walter Reed Army Medical Center
Coauthor(s): Theresa Dressler Conologue, DO, FAAD, Physician, Department of Dermatology, Geisinger Medical Center; Kristina Shaffer, MD, MPH, Consulting Staff, Department of Dermatology, Dermatology Consultants
Contributor Information and Disclosures

Updated: May 5, 2009

Introduction

Background

Dupuytren contracture is a palmar fibromatosis of uncertain etiology. Reports were first seen in 17th century European medical literature, well before the eponymous Baron Dupuytren, a prominent French surgeon, performed his first palmar fasciotomy in 1831. Dupuytren presented his findings at a lecture, the exact words of which were subsequently disseminated widely by his students, leading to the adoption of his name for the condition.

The syndrome is characterized by fibrosis of the palmar fascia leading to flexural contraction of the digits, which is often progressive. Both the proximal interphalangeal (PIP) joint and the metacarpophalangeal (MCP) joint may be affected. Although many cases appear to be idiopathic and without coexistent conditions, a variety of associated diseases have been reported.

Therapies include conservative medical and surgical modalities. Although the condition is not fatal, significant morbidity can occur if patients remain untreated.

For additional information, the eMedicine articles Dupuytren Contracture (orthopedic surgery focus), Dupuytren Contracture (rheumatology focus), and Dupuytren Contracture (physical medicine and rehabilitation focus) may be helpful.

Pathophysiology

The etiology and the mechanisms of formation have not been fully determined. The disease affects the palmar fascia, not the tendons, although the cordlike fascial thickening can be mistaken for a thickened tendon.

In the fascia, 3 stages have been described, as follows:

• Proliferative phase: Local fascial fibroplasia and development of a nodule, in which myofibroblasts proliferate, occur.
• Involutional phase: Myofibroblasts align themselves along the tension lines within the nodule.
• Residual phase: The nodular tissue disappears, leaving acellular tissue and thick bands of collagen. The ratio of type III collagen to type I collagen increases, which is the reverse of the normal pattern in the palmar fascia.

These cellular changes are similar to those that occur in localized microvascular ischemia and scar formation, leading some authors to believe that these factors may be the causes of the initial fibroblast and myofibroblast proliferation. Microvascular ischemia occurs as a result of the conversion of adenosine triphosphate to hypoxanthine, which is then oxidized by xanthine oxidase. This conversion releases free radicals, which induce fibroblast proliferation and the production of interleukin (IL)–1.

Various mediators released by platelets and macrophages have been implicated in the pathogenesis of Dupuytren contracture. These mediators include IL-1 and transforming growth factors (TGFs)–beta1 and –beta2. TGF-beta1 and –beta2 have 4 main effects, as follows:

• Differentiation of fibroblasts to myofibroblasts
• Increased production of components of the extracellular matrix, including collagen type III
• Splicing of fibronectin
• Activation of platelets to produce lysophosphatidic acid (LPA)

The linkage of alpha5-beta1 integrin to extracellular fibronectin, as well as the interaction of TGF-alpha and epidermal growth factor-receptor during the proliferative and involutional phases,¹ appear to have a role in enhancing tissue contractility in palmar fibromatosis. LPA and prostaglandin factor 2 are agonists that induce myofibroblast contraction. Levels of nerve growth factor, which induces fibroblast transformation to myofibroblasts, were also found to be increased in persons with Dupuytren tissue, especially during stages II-III.

Inflammation and skin tension may also cause fibromatosis. Histologically, the lesion shows characteristic bundles of fibroblasts separated by collagen fibers. Multinucleated giant cells may also be present. Lymphocytes, macrophages, and increased numbers of S100-positive Langerhans cells and CD45⁺ cells have been found in nodules and at dermoepidermal junctions. One report suggested a role of factor XIIIa⁺ cells in the affected tissue.

The interaction of matrix metalloproteinases (MMPs), tissue inhibitor of metalloproteinases (TIMP), and A disintegration and metalloproteinase domain with thrombospondin motif (ADAMTS) is also responsible for Dupuytren changes. In particular, levels of MMP-1, MMP-2, MMP-3, MMP-7, MMP-14, TIMP-1, TIMP-2, and ADAMTS-14 are all increased in affected tissues, resulting in increased collagen biosynthesis, decreased collagenolysis, and contraction.^2,3

Continuing research into the pathogenesis of Dupuytren contracture has yielded information that may be valuable in understanding and developing new therapies for this disease, as follows:

• TGF-beta1 at 1-10 ng/mL induces myofibroblast proliferation, leading to contraction. However, according to one report, at 20-30 ng/mL, negative feedback inhibition of TGF-beta1 occurs, resulting in decreased myofibroblast activity.
• N -acetyl-L-cysteine (NAC), a substance that has antifibrotic properties in hepatic stellate cells and rat fibroblasts, has also been shown to down-regulate the Smad signaling pathway (downstream of TGF-beta1), leading to decreased expression of fibrogenesis-related proteins.⁴
• A recent study demonstrated a decrease in expressed myoglobin, an oxygen-transporting protein, and an increase in ROR2 (tyrosine kinase – like orphan receptor 2), a protein associated with other hand disorders.⁵

Frequency

United States

No prospective studies have been performed to determine the incidence of Dupuytren contracture, but a cross-sectional study looking at the prevalence in 5000 patients admitted to a New York City hospital for unrelated conditions showed a rate of 4.8%, with a male-to-female ratio of 3:1.

International

Studies have been performed worldwide, yet a range of frequencies has been reported. The highest frequency was reported in Scotland, where 200 patients were examined and 39% of men and 21% of women older than 60 years were affected with Dupuytren contracture. In Japan, 19.7% of men and 9% of women older than 60 years in nursing homes had the disease. In Spain, the disease was seen in 9.9% of individuals aged 45-54 years, while the rate increased to 25.5% in patients older than 75 years. In Iceland, rates of 7.2% in men aged 45-49 years and 39.5% in men aged 70-74 years have been reported.

Mortality/Morbidity

No mortality occurs from this disease. Morbidity occurs from progressive contraction of the affected digits, resulting in both cosmetic and functional disability. With severe flexion deformity, the nail of the affected digit may penetrate the palmar skin. Infection secondary to this trauma has been reported.

Race

Most patients appear to be of Northern European descent, especially Scotland and the Scandinavian countries. The disease is less likely to occur in African and Asian populations. Case reports and series have shown that persons of any race can be affected.⁶

Sex

All studies show a male preponderance earlier in life, with men presenting for treatment in the fifth decade and women presenting a decade later. Typical male-to-female ratios of 3-9:1 have been reported. By the ninth decade of life, no sexual difference in incidence is found. Men are more likely than women to undergo surgery for the disease.

Age

The average age of onset in men is in the sixth decade, with onset occurring later in women, in the seventh decade. Dupuytren contracture has been reported in children and infants⁷ but is considered rare.

Clinical

History

Patients describe feeling a knot or thickening on the palmar surface or, less frequently, on the digits, typically the proximal palmar aspect. Often, the thickening has been present for many years and may be slowly progressive.

The fourth digit (ring finger) is most frequently affected, followed by the fifth digit. The disease can be bilateral, but it is generally not symmetric in severity. Hand dominance is not a factor. Nodules typically are painless. Tenosynovitis can develop and lead to pain when the nodules are large. With progressive disease, flexion deformity can develop. Patients report an inability to straighten the fingers.

Dupuytren diathesis, first described in 1963 by Hueston, is seen in patients with an early age of onset (<40 y in men, <50 y in women), bilateral hand involvement, a strong family history, and ectopic lesions. These are considered risk factors for disease recurrence and extension. More recently, a proposal to modify these factors includes male sex as another risk factor.⁸

Related fibromatoses, including Peyronie disease (affecting the penis), Ledderhose disease (affecting the plantar surface), and Garrod knuckle pads (affecting the dorsal PIP joints), may occur. Wrist involvement has been described,⁹ but whether this is a variant of Dupuytren contracture or another similar process involving myofibroblast proliferation is uncertain.

Physical

Physical findings depend on the stage at which the disease is observed. Although the fourth and fifth digits are most commonly involved, any digit can be affected.

• In the earliest stage, localized thickening of the palmar skin and underlying subcutaneous tissue with loss of skin mobility occurs. A depression, puckering, or pitting of the skin may be present in the affected area.
• With the nodular stage, nodules initially are palpable; later, nodules are visible. Nodules are firm, fixed, and usually well localized. When the disease affects the palm, the nodules are usually located adjacent to the palmar crease, typically in line with the ring (fourth) and/or little (fifth) fingers. Digital nodules are located near the PIP joint or at the MCP joint. Of those involving the little finger, a quarter have abductor digiti minimi involvement.¹⁰
• In the cord stage, the cord is a linear thickening and can resemble the tendon. Progressive contraction of the cord leads to a flexion deformity of the digit. Flexion deformity usually occurs at the MCP joint. Disease located in the digits produces flexion at the PIP joint. MCP joint contracture should be measured while passive extension is applied to the PIP joint. PIP joint contracture is measured while the MCP joint is held in flexion. These maneuvers eliminate artificial contractures. When 30° of flexion deformity is present at the MCP joint, the patient is unable to place the palm flat against a hard surface.

Knuckle pads may be present on the dorsal aspect of the PIP joints, and this indicates more aggressive disease. Additionally, swan-neck deformities and boutonnière deformities have been reported with this disease.

Causes

The cause of Dupuytren contracture remains unknown. Genetic factors are thought to play a role in Dupuytren disease; however, currently no link has been established.¹¹ Still, one study derived a sibling recurrence-risk ratio of 2.9 (range, 2.6-3.3; 95% confidence interval for population prevalence), with a lower age of onset and more severe disease in patients with a positive family history.¹² Furthermore, DNA microarray analysis has demonstrated that the gene MafB, involved in tissue development and cellular differentiation, is up-regulated in Dupuytren cord tissue.¹³

A separate analysis of an autosomal dominant pattern of inheritance, with incomplete penetrance, in 5 generations of a Swedish family, mapped the affected gene (not yet identified) to 16q.¹⁴ Another study of 20 patients with apparent maternal inheritance identified a polymorphism in the mitochondrial 16s rRNA region present in 90% of their DNA.¹⁵ Others believe that Dupuytren contracture has a multifactorial inheritance, similar to diabetes or hypertension.

Many conditions or factors have been associated with Dupuytren contracture. The following have shown the strongest associations:

• Local trauma or injury: Many hand surgeons believe that trauma to the hand or the distal part of the forearm, such as falling on an outstretched hand, may precipitate the onset.
• Alcoholic liver disease: Individuals with alcoholism and liver disease have an increased prevalence of Dupuytren contracture (approximately 20%) compared with control populations. Patients with liver disease from other causes do not appear to be at increased risk. The reason for this is unknown, and some studies¹⁶ have disputed the association.
• Diabetes: Of patients with Dupuytren contracture, 5% have diabetes. At greatest risk are persons with type 1 diabetes mellitus, followed by those who take metformin and sulfonylureas. One theory suggests that as many as two thirds of patients with long-standing type 1 diabetes (>20 y) have some degree of Dupuytren contracture. Persons with type 2 diabetes with Dupuytren disease have a 4-fold increased risk of developing microalbuminuria compared with type 2 diabetes patients without Dupuytren disease.
• Smoking: A 3-fold increased risk for Dupuytren contracture is seen in individuals who smoke, even when studies control for alcohol use, perhaps due to microvascular impairment.
• Autoantibodies to connective tissue: Significant associations have been found with HLA-DRB1*15,¹⁷ HLA-DR3 and autoantibodies to collagen types I-IV.
• Androgen receptors: Two studies have shown increased sensitivity to androgens in the palmar fascia.^18,19 This may account for the male predominance of the disease.
• Manual work: In general, only persons who work in occupations exposed to vibration appear to be at increased risk.
• Epilepsy and use of epileptic medications: Although implicated in previous studies, little conclusive evidence has been reported to link epilepsy and antiepileptic medications to the development of Dupuytren contracture. Phenobarbitone, in particular, results in increased LPA levels.

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