Dupuytren Contracture

Etiology

Dupuytren disease is a genetic disorder that often is inherited in an autosomal dominant fashion, but is most frequently seen with a multifactorial etiology. It is associated with diabetes, seizure disorders, smoking, alcoholism, HIV, and vascular disease.[2] Of note, occupation and activities have not been shown to be risk factors. Ectopic manifestations beyond the hand can be seen in Ledderhose disease (plantar fascia), 10% to 30%; Peyronie disease (Dartos fascia of the penis), 2% to 8%; and Garrod disease (dorsal knuckle pads), 40% to 50%.

Epidemiology

This condition is most commonly seen in populations of Northern European/Scandinavian descent.[3]  In a Denmark based twin study by Larsen et. al. in 2015, the estimated the overall heritability as 80%.[4] It is relatively uncommon in Southern European and South American populations and is rare in Africans and Asians. Males are affected by a 2:1 ratio compared to women, with the disease also affecting men more severely. Younger age of onset is also associated with increased severity of disease progression. In Asian populations, the palm is more likely to be involved than the digits and thus it is often not noticed.

Pathophysiology

The pathophysiology of Dupuytren disease involves abnormal myofibroblastic growth in the hand, predominantly composed of type III collagen. Numerous cytokines are involved including interleukin-1, transforming growth factor beta-1, transforming growth factor beta-2, epidermal growth factor, platelet-derived growth factor, and connective tissue growth factor. Dupuytren contracture progresses through three phases: (1) proliferative, (2) involution, and (3) residual. The proliferative phase has a characteristically high concentration of immature myofibroblasts and fibroblasts arranged in a whorled pattern. In the involution phase, fibroblasts become aligned in the longitudinal axis of the hand following lines of tension. In the residual phase, relatively acellular collagen-rich chords remain causing contracture deformity. 

The disorder is not always progressive and in at least 50-70% of patients, it may stabilize or even regress.

Transformation of the normal fascial bands into pathological cords is what causes unique deformities of the hand. Central cords originate from the pretendinous bands and cause skin pitting and metacarpal phalangeal (MCP) joint contracture. Natatory cords are responsible for webspace contractures. Spiral cords are the most important in the disease process and can cause proximal interphalangeal (PIP) contracture. A spiral cord originates from four main structures: (1) pretendinous band, (2) spiral band, (3) Lateral digital sheath, and (4) Grayson ligament.  Surgeons should be aware that the spiral cord causes displacement of the neurovascular bundle centrally, superficially, and proximally in the digit.[5] Of note, the Cleland ligament and the transverse ligament of the palmar aponeurosis are not involved in Dupuytren disease.

Risk factors for increased severity and recurrence of disease after treatment include male gender, onset before age 50, bilateral disease, sibling/parent involvement, or the presence of Garrod pads, Ledderhose, or Peyronies diseases.

There are also genetic factors involved in Dupuytren disease.  In a genome-wide association study (GWAS) of Dupuytren disease by Dolmans et. al.[6] in 2011 identified nine susceptibility genetic loci. Six of these loci contained genes encoding proteins involved in Wnt signaling, including RSPO2, WNT4, and SRFP4. Research has further progressed and now there are 26 known loci described. Additionally, Wnt7b has been found to be expressed in Dupuytren nodules.[7] Much remains to be discovered in our understanding of the molecular signaling pathways involved in the progression of Dupuytren disease.  Future work focused on how changes in Wnt signaling influence stromal cell phenotypes may eventually help to identify new targets for the treatment of disease.

Histopathology

Histologic analysis reveals myofibroblasts and fibroblasts.[8] Myofibroblasts have contractile actin microfilaments which align with the long axis of the cell. Myofibroblasts interconnect themselves with fibronectin and extracellular fibrils. Type III collagen predominates in the extracellular matrix. Interestingly, about 10% of the cells in Dupuytren nodules are comprised of immune cells, the major of which are macrophages and lymphocytes. Nodules are found to be highly cellular with densely packed myofibroblasts, whereas cords have relatively few cells and are mainly composed of fibroblasts.[9] Macrophages and lymphocytes are responsible for the secretion of proinflammatory cytokines including interleukin-6 (IL-6), IL-8, and tumor necrosis factor (TNF). Dupuytren nodules have been discovered to contain dense T-cell infiltrates, suggesting it is a T cell-mediated autoimmune disorder. [10] This is also supported by a recent study showing an activated T-cell infiltrate next to blood vessels within Dupuytren nodules. Further testing in-vitro has shown cells expressing restricted T-cell receptors.[11]  These findings support the concept that a local immune reaction may be caused by microvascular changes in the hand that is triggered by an autoantigen. 

History and Physical

Dupuytren disease starts as a palpable nodule in the palm, usually at the distal palmar crease. The nodules enlarge into cords and early in the disease, patients may present with just palpable cords along the palm. As the cords thicken and shorten, they cause fixed flexion contractures of the fingers at the MCP and PIP joints. At this stage, patients typically present with loss of range of motion of the hand and palpable cords in the palm extending into the affected digits. Nodules, cords, and finger contractures are pathognomic of Dupuytren disease. Rarely patients report pain.

The 4th digit is most often affected, followed by the 5th digit. Even when the disorder is bilateral, the severity may not be symmetrical. In most cases, palpation of the nodules does not elicit pain unless the ulnar nerve is compressed. Further, the nodules may become tender in the presence of tenosynovitis.

Physical findings:

• Blanching of the skin when the finger is extended
• Proximal to the nodules, the cords are painless
• Pits and grooves may be present
• The knuckle pads over the PIP joints may be tender
• If the plantar fascia is involved, this indicates more severe disease (Ledderhose disease)
• The tabletop test (Hueston) is performed by having the patient attempt to place the palm flat on the exam table. If there is any flexion contracture deformity, the patient will be unable to straighten the fingers, resulting in a positive test. [12]

Evaluation

X-rays of the hand are not needed but may be obtained to examine for bony abnormalities like arthritis that may contribute to the loss of range of motion.

Additionally, laboratory workup to rule out diabetes is recommended. Ultrasound may demonstrate thickened palmar fascia and nodules.

Treatment / Management

Indications for treatment are based on the effects of the disease on the patient's quality of life. Many patients with a positive tabletop test, MCP contracture of 30 degrees, or PIP contracture of 15 to 20 degrees will elect to have treatment.

Treatment options consist of conservative management, needle aponeurotomy, collagenase injection, and/or surgical resection and fasciectomy.[13] (B3)

Conservative Management

Observation is appropriate for individuals with painless stable disease and no impairment in function. Follow-up every 6 months may be done to assess the progression of the disorder.

Physical and occupational therapy including ultrasonic waves and heat can help during the early stage of the disease. Some patients may also benefit from a brace/splint to stretch the digits. The range of motion of the fingers is necessary to prevent adhesions.

Corticosteroid injections may be beneficial for some patients, especially those with painful nodules. Unfortunately, the steroid injections do not work in all patients, and recurrence of up to 50% have been reported. More important, corticosteroid injections can lead to fat atrophy, pigmentation change and there is the potential to cause rupture of the tendons.

Other treatments that have been tried include the use of tamoxifen, anti-tumor necrosis factor agents, 5 fluorouracil, imiquimod, and botulinum toxin. There is no evidence that any of these treatments are superior or work for everyone.

Radiation therapy may work during the early phase of the disease only but is also associated with a significant number of complications. 

Needle Aponeurectomy

Needle aponeurotomy is typically reserved for mild contractures. The procedure is minimally invasive and is often performed in an office setting. A needle is used to break up the cord. The digit is then manipulated, and the patient wears a night extension splint.  Metacarpal-phalangeal joint contractures have the greatest improvement. The benefit of this procedure is that it is minimally invasive and has the potential for immediate results. Disadvantages include iatrogenic injury to nerves and tendons and 58% recurrence rates[14].

Collagenase Injection

Collagenase injections provide a minimally invasive treatment derived from Clostridium Histolyticum. The injected enzyme is a metalloprotease that lyses collagen (sparing Type IV collagen which is needed in the basement membrane of blood vessels and nerves). Treatment typically consists of 0.25 mL for MCP and 0.20 mL for PIP contractures delivered subcutaneously directly into the cord with a needle. The affected digit is manipulated under local anesthesia at 24 to 48 hours after injection. Night extension splinting is maintained for 6 months. Collagenase injections have been shown to result in a 75% contracture reduction with a 35% recurrence rate. Complications of injections include edema, skin tearing, tendon rupture, complex regional pain syndrome, and pulley rupture.

Surgery

Surgical fasciectomy can be either partial or total. Partial palmar fasciectomy entails the limited resection of diseased tissue within a ray.  Dissection generally is performed from proximal to distal as this usually allows for the identification of neurovascular structures before encountering the spiral cord. Incisions are customized to each patient in a Brunner zigzag pattern. A V-Y incision and Z-plasty can also be used to lengthen contracted skin. Care must be taken to preserve the neurovascular bundles. The recurrence rate at 1 to 2 years is 30%, 15% at 3 to 5 years, and less than 10% after ten years.

Total palmar fasciectomy can also be performed but is infrequently used as it requires resection of all of the palmar and digital fascia, including nondiseased tissue. It is indicated in chronic digital cords, infiltrating disease, or recurrence after a partial surgical procedure.

Complications of fasciectomy include skin necrosis, hematoma (most common complication), flare reaction, neurovascular injury, digital ischemia, swelling, and infection. [15](B3)

Irrespective of the treatment, recurrence is common with all treatment modalities, approaching 20-50% at 5 years.

Differential Diagnosis

Dupuytren disease should be distinguished from other diseases of the hand including stenosing flexor tenosynovitis, flexor tendonitis, ganglion cysts, ulnar neuropathy, and soft tissue tumors. Unlike Dupuytren disease, stenosing tenosynovitis presents as a triggering finger that is painful with flexion followed by the inability to actively extend the finger.  The examiner may also be able to palpate a nodule at the A1 pulley situated near the MCP joint. In this setting, one must decipher a nodularity to the flexor tendon, a cyst that is moveable and arising from the metacarpal-phalangeal joint vs a soft tissue tumor. 

Prognosis

Dupuytren contracture has variable morbidity depending on the severity of the disease. Contractures of the PIP and MCP joint can interfere with daily living activities, ability to work, and lifestyles. In some patients, the nodules may be painful. In others, there may also be associated with Peyronie disease or involvement of the knuckle pads- these associations usually tend to be associated with severe disease. 

Complications

Complications of surgical treatment include wound edge necrosis, hematoma, nerve injury, digital ischemia, infection, swelling, recurrence, and postoperative flare. Digital ischemia can be due to direct damage to the vascular supply of the digit or because of stretch injury to vessels in digits with a history of prolonged flexion contracture. As noted, the spiral cord causes central and palmar displacement of the neurovascular bundles, increasing their susceptibility to injury.

Dupuytren flare reaction is pain with diffuse swelling, hyperesthesia, redness, and stiffness. Treatment of this complication consists of steroids, cervical sympathetic block, therapy, and A1 pulley release. There is no increased risk of complex regional pain syndrome (CRPS) if carpal tunnel release is performed with fasciectomy.[16]