Dupuytren's Contracture: Pathogenesis and Management Strategies

Dupuytren’s contracture is a flexion deformity of the hand caused by progressive fibroproliferation. Within weeks or months, palpable nodules and cords develop in the fascia, the fibrous layer of tissue beneath the skin of the palm and fingers. These nodules and cords cause flexion contractures in which the finger joint cannot be straightened either actively or passively.

Although finger contractures were first observed more than 400 years ago, widespread recognition of the underlying disease did not occur until the 1830s following the work of French surgeon Baron Guillaume Dupuytren.

Epidemiology

Due to the high prevalence (30%) of the disease in white Northern European and Norwegian men aged 60 years or older, Duputyren’s disease is often called "Viking" or "Norse" disease. However, there is no evidence that the disease originated in the Scandinavian population.

Prevalence increases with age, from 12% in adults 55 years or older to 29% in those 75 years or older. Initially, Dupuytren’s disease was thought to only occur in men; however, that has been disproven with a current estimated male to female ratio of approximately 6:1.

Genetics

A genetic component of Dupuytren’s disease shows that Northern European ancestry increases the likelihood of contracting the disease. Additionally, inheritance is believed to be autosomal dominant, with one being three times more likely to develop Dupuytren’s disease if a sibling has the disease.

While no single gene has been identified, dysfunction of numerous genes can cause a disruption in the ability to regulate collagen formation and breakdown. A genome-wide association study in 960 Dutch individuals with Dupuytren’s disease identified 11 single-nucleotide abnormalities from nine different genetic loci. Furthermore, six of the nine loci identified also contain genes for the regulation of fibroblast proliferation and differentiation. Interference with these genes could alter the function of fibroblasts and cause the formation of nodules or cords in the fascia of the hand.

Pathophysiology

The progression of Dupuytren’s contracture is the result of diseased fascial bands (or aponeurosis), which can be damaged by repetitive trauma commonly associated with manual work.

Repeated fascial trauma, along with other risk factors described below, promotes the release of free radicals , which stimulates the release of interleukin-1, an inflammatory cytokine responsible for transforming growth factor beta (TGF-beta). This promotes the proliferation of myofibroblasts and the production of type III collagen instead of the type I collagen found in healthy fascia.

With continued trauma, nodules form on and around the fascia; Over time, type III collagen attaches to the nodules and connects them, forming cords on top of and around the fascia. The nodules and cords constrict the fascia and can extend and restrict the extension of the distal fingers, causing the deformity known as Dupuytren’s contracture.

The most commonly involved joints are the metacarpophalangeal (MCP) joint or knuckle, followed by the proximal interphalangeal (PIP) joint and the distal interphalangeal (DIP) joint, which is rarely affected.

Risk factors and clinical presentation

Risk factors for Dupuytren’s disease include repetitive trauma to the hand, such as with manual labor, excessive alcohol intake, smoking, epilepsy, diabetes, age, and genetics, including male sex.

The clinical presentation can differ significantly depending on early or advanced disease. The third to fifth fingers (the thumb is finger 1 and the little finger is finger 5) are most affected, and in the early stage of the disease, patients may experience dimpling or thickening of the skin.

As firm, painless nodules develop along the inner fascia of the palm, the patient may notice a progressive flexion contracture (a bent joint that cannot be straightened), which is more common in advanced disease. Furthermore, the clinical presentation varies depending on the fascia and fingers affected.

With advanced disease, collagen adheres to the nodules and forms thick cords that constrict the fingers and deform the hand. Cords extending up the fingers may be visible and cause extensive hand contraction.

While most common in the palms of the hands, Dupuytren’s disease can affect other areas commonly exposed to trauma, such as the feet.

In advanced disease, patients may not be able to put their hand on a table. Advanced progression can also cause Garrod’s nodes (knuckle pads over the dorsal PIP joint). These patients may develop Ledderhose disease (plantar fibromatosis) or Peyronie’s disease (penile fibromatosis).

Diagnostic criteria and methods

Dupuytren’s disease is usually diagnosed based on the patient’s presentation, the patient’s history, and any effects on activities of daily living. The Hueston table test is used to assess disease progression and may indicate the need for corrective measures. The test is considered positive for Dupuytren when the patient cannot place the hand flat on a table, indicating more than 30° of MCP contracture.

Staging and Classification

There are different types of classification and staging available for Dupuytren’s disease. Luck’s classification, based on the cellular process of disease progression, is divided into proliferative, involutional and residual stages . The proliferative stage indicates large myofibroblasts with immature fibroblasts; the involutional stage denotes a dense network formed by myofibroblasts and a higher proportion of type III collagen to type I collagen; and in the residual stage , an extensive matrix of dense collagenous tissue has formed with fibroblasts as the predominant cell type. Disease severity is assessed using the Tubiana staging system.

Treatment

Treatment options for Dupuytren’s disease are not curative but symptomatic , and primarily include surgical and non-surgical measures to correct the contracture. Management is patient-specific and uses a graded approach based on disease severity, risk of complications, concern for recurrence, and cost.

Percutaneous needle aponeurotomy or Clostridium histolyticum collagenase injections may be considered in mild to severe disease, with more invasive therapies such as percutaneous needle fasciotomy or limited fasciotomy reserved for advanced disease or rapid recurrence after initial treatment .

Collaborative treatment plans should always be the goal, with patients aware of the progressive nature of the disease.

Procedure-based modalities are used in the setting of symptomatic contractures, and surgery has been considered the standard of care in the treatment of Dupuytren’s contracture.

With the advancement in interventions and multiple treatment modalities to choose from, the severity of the disease should guide which procedure the patient receives. Additionally, the recurrence rate after procedures, risk of complications, and adverse events should be taken into account in the decision.

Non-surgical options

Clostridium histolyticum collagenase injections: Collagenase injections are approved by the FDA for the treatment of Dupuytren’s contracture in adults with a palpable cord. The drug contains two clostridial collagenases that hydrolyze collagen acting as an enzymatic fasciectomy . The treatment consists of injecting directly into the cords that cross the affected joint. The fingers are then manually manipulated to further cut the cord and release the contracture. The dosage varies depending on the joint, with the MCP joint being necessary 0.25 ml and the PIP joint 0.20 ml. 8

The phase III JOINT I and JOINT II clinical trials evaluated the safety and efficacy of collagenase C histolyticum injections in adult patients with Dupuytren’s contracture who had a fixed flexion contracture of >20°.

Reduction of the primary contracture endpoint to £5° of full extension was achieved in 497 of 879 (57%) joints, with 292 joints demonstrating a response within 7 days. Additionally, 369 (70%) contractures at the MCP joint and 129 (37%) at the PIP joint achieved clinical success. Of note, 625 (71%) joints did not require a second injection and 780 (89%) did not require a third.

The most common adverse effects include peripheral edema, contusion, hematomas, injection site pain, skin tenderness, lymphadenopathy, and pruritus. Treatment-emergent complications that occur in <1% of patients include complex regional pain syndrome, flexor tendon rupture, and anaphylaxis.

Triamcinolone acetonide injections : Triamcinolone acetonide injections have also been studied for use in Dupuytren’s contracture. First, the area is pretreated with a local anesthetic such as lidocaine. Triamcinolone is then injected directly into the nodules, which inhibits TGF-beta-1 and decreases fibroblast activity. Triamcinolone acetonide injections offer the benefit of limited recovery time compared to surgical measures.

Triamcinolone acetonide injections were studied as primary treatment in 63 patients (60% male; mean age 55 years) with Dupuytren’s nodules. After an average of 3.2 injections per nodule, 97% of patients experienced a reduction in nodule size of approximately 60% to 80%.

However, within 1 to 3 years, 50% of patients experienced disease recurrence with nodule growth requiring additional treatments with triamcinolone acetonide.

Furthermore, triamcinolone acetonide injections as an adjuvant treatment after needle aponeurotomy (described below) showed a lower total active extension deficit at 6 months lasting up to 24 months compared to needle aponeurotomy without triamcinolone acetonide injections. triamcinolone. However, at 24 months the differences between the groups ceased.

Surgical options

Surgical intervention, which is usually indicated in patients with 30° MCP contracture or any PIP contracture (usually >15°), involves removal of the fascia either as fasciotomy (division of the cord to release the contracture, without removal of the cord) or fasciectomy (removal of diseased fascia, including the cord and nodule) with excision of the diseased fascia (limited) or a skin graft (dermofasciectomy).

MCP joints are more likely to respond to surgery than PIP joints. Percutaneous needle aponeurotomy fasciotomy has a higher reoperation rate than limited fasciectomy or dermofasciectomy; however, there are fewer complications overall. Patients may undergo more than one procedure, which may or may not have been the primary procedure.

Fasciotomy – Percutaneous needle fasciotomy (also known as percutaneous aponeurotomy or needle fasciotomy) is a minimally invasive procedure performed on multiple contractures during the same session in which a hypodermic needle is repeatedly inserted into the cord in multiple positions.

The corresponding finger is manually manipulated until maximum passive extension occurs. Because it can be performed in an office setting under local anesthesia, patients with small palpable cords at the MCP and PIP joints are good candidates.

Results from a retrospective study of 52 patients (56 joints) showed a 77% improvement in MCP and PIP joint extension, but the majority of contractures (65%) recurred within 3 to 4 years.

Another study comparing needle fasciotomy with limited fasciectomy reported much lower recurrence rates with the latter, 84.9% versus 20.9%. Complications with needle fasciotomy are minimal, but can include nerve damage, skin lacerations, and flexor tendon injuries.

During an open fasciotomy, the cords are cut with a scalpel using direct vision, which protects the neurovascular structures because they are less likely to be damaged. After the procedure, recovery usually occurs within several weeks with minimal complications.

Results from a retrospective study of 1077 patients (865 men and 212 women) who received open fasciotomy showed that 93% of affected joints achieved complete release; 13.5% needed a second operation an average of 46 months after the initial procedure.

Fasciectomy : A limited fasciectomy is the most commonly performed operation for Dupuytren’s contracture. Due to the invasive nature of the procedure, general or regional anesthesia is often required.

Patients are advised to flex and extend their fingers as soon as the anesthesia wears off. It is effective for patients with moderate to severe disease and has shown a success rate of 94% with MCP joints and 46% with PIP joints.

Recurrence rates of 23% to 38% have been reported. Additionally, patients who underwent limited fasciectomy reported significantly higher satisfaction scores than patients who received collagenase injection and lower recurrence rates than with needle fasciotomy.

The most aggressive procedure is a dermatofasciectomy . Typically, dermato-fascietomy is reserved for those with advanced disease or who have failed other procedures. Younger patients are also candidates.

In a study of 143 procedures (103 patients, 83% men, mean age 69.2 years), dermatofasciectomy had a 5.8-year follow-up recurrence rate of 11.6%. Prolonged rehabilitation and additional postoperative complications are associated with both procedures.

Role of the Pharmacist

Although Dupuytren’s disease is usually diagnosed and treated by the patient’s primary care provider, pharmacists play a role in both pre-treatment and post-treatment care. Pharmacies serve as health education centers for their communities, and pharmacists can answer any questions and refer patients when cords or nodules are present.

The pharmacist may also recommend risk mitigation techniques, such as blood sugar control or smoking cessation. Finally, pharmacists may recommend post-treatment care, including wound management, scar prevention methods, and comfort techniques, including protective gloves or over-the-counter pain management.