Dupuytren Contracture

Etiology

Dupuytren disease is a genetic disorder often 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 are not 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]  A Denmark-based twin study by Larsen et al in 2015 estimated the overall heritability to be 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; 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 include 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 3 phases: proliferative, involution, and 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 causes unique hand deformities. 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 part of the disease process and can cause proximal interphalangeal (PIP) contracture. A spiral cord originates from 4 main structures: pretendinous band, spiral band, lateral digital sheath, and 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 is that 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 9 susceptibility genetic loci. Six loci contained genes encoding proteins involved in Wnt signaling, including RSPO2, WNT4, and SRFP4. Research has progressed, and now, 26 known loci have been described. Additionally, Wnt7b is 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 identify new targets for treating disease.

Histopathology

Histologic analysis reveals myofibroblasts and fibroblasts.[8] Myofibroblasts have contractile actin microfilaments that align with the cell's long axis. 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, most of which are macrophages and lymphocytes. Nodules are 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. Dupuytren nodules have been discovered to contain dense T-cell infiltrates, suggesting it is a T-cell-mediated autoimmune disorder.[10] A recent study also supports this by showing an activated T-cell infiltration 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 are 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 patients may present with palpable cords along the palm early in the disease. 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 do 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 of Dupuytren contracture include:

• 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 a 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 cannot straighten the fingers, resulting in a positive test.[12]

Evaluation

X-rays of the hand are unnecessary 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 elect to have treatment. Treatment options consist of conservative management, needle aponeurotomy, collagenase injection, 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 disorder's progression. 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 importantly, corticosteroid injections can lead to fat atrophy and pigmentation change, and there is the potential to cause rupture of the tendons. Other treatments that have been tried include tamoxifen, anti-tumor necrosis factor agents, 5 fluorouracil, imiquimod, and botulinum toxin. There is no evidence that 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 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 resulted 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 is generally performed from proximal to distal, as this usually allows for identifying 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 10 years. Total palmar fasciectomy can also be performed but is infrequently used as it requires resection of all 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] Irrespective of the treatment, recurrence is common with all treatment modalities, approaching 20-50% at 5 years.(B3)

Differential Diagnosis

Dupuytren disease should be distinguished from other hand diseases, 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 extend the finger actively.  The examiner may also palpate a nodule at the A1 pulley near the MCP joint. In this setting, one must decipher a nodularity to the flexor tendon, a moveable cyst arising from the metacarpal-phalangeal joint, versus a soft tissue tumor. 

Prognosis

Dupuytren contracture has variable morbidity depending on the severity of the disease. PIP and MCP joint contractures can interfere with daily living activities, workability, and lifestyles. In some patients, the nodules may be painful. In others, they 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 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 if carpal tunnel release is performed with fasciectomy.[16]