Dupuytren Contracture Flashcards
Overview
Dupuytren disease is a fibrosing disorder that results in slowly progressive thickening and shorting of the palmar fascia and leads to debilitating digital contractures, particularly of the metacarpophalangeal (MCP) joints or the proximal interphalangeal (PIP) joints. This condition usually affects the fourth and fifth digits (the ring and small fingers)
Dupuytren contracture belongs to the group of fibromatoses that include plantar fibromatosis (Ledderhose disease), penile fibromatosis (Peyronie disease), and fibromatosis of the dorsal PIP joints (Garrod nodes or knuckle pads). [1] Although many cases appear to be idiopathic, various associated diseases have been reported.
Dupuytren contracture is most commonly observed in persons of Northern European descent and affects 4-6% of Caucasians worldwide. [2] Many individuals have bilateral disease (45%); in unilateral cases, the right side is more often affected. [3] The ring finger is most commonly involved, followed by the fifth digit and then the middle finger. The index finger and the thumb are typically spared. See Epidemiology and Presentation.
Although the cause of Dupuytren disease is unknown, a family history is often present. Males are three times as likely to develop disease and are more likely to have higher disease severity. [4, 5] Male predominance may be related to expression of androgen receptors in Dupuytren fascia. See Etiology and Epidemiology.
Other potential risk factors include manual labor with vibration exposure, prior hand trauma, alcoholism, smoking, diabetes mellitus, hyperlipidemia, Peyronie disease, and complex regional pain syndrome.
Rheumatoid arthritis seems to protect against the development of Dupuytren disease.
Therapies include conservative medical and surgical modalities. Although the condition is not fatal, significant morbidity can occur if patients are untreated
Stages of Dupuytren disease
Dupuytren disease occurs in the following three stages:
- Proliferative phase - During this phase, myofibroblasts proliferate and a nodule develops. In early disease, some patients may report tenderness and discomfort associated with the nodules. The associated pain is thought to be due to nerve fibers embedded in the fibrous tissue or compression of local nerves. [8] On physical examination, palmar skin blanching is seen with finger extension.
- Involutional phase - In this phase the disease, spreads along the fascia and into the fingers resulting in the development of a cord. Myofibroblasts are the predominant cell type during this phase and align themselves along tension lines within the nodule
- Residual phase – During the residual phase, the disease continues to spread into the fingers and the cord tightens creating a contracture. The nodular tissue disappears as do the myofibroblasts and acellular tissue with thick bands of collagen remain.
Dupuytren disease is not always progressive, however. A prospective study in 247 Dutch participants with primary Dupuytren disease with follow-up at intervals of 3 to 6 months found that in up to 75% of patients, the disease stabilizes or even regresses
Grades of severity
The grading system for Dupuytren disease severity is as follows:
Grade 1 - Thickened nodule and band in the palmar aponeurosis; may have associated skin abnormalities
Grade 2 - Development of pretendinous and digital cords with limitation of finger extension
Grade 3 - Presence of flexion contracture
Pathogenesis/Etiology
Although the underlying etiology for the development of Dupuytren disease is uncertain, the basic pathophysiology involves fibroblast proliferation, and collagen deposition leading to contractures of the palmar fascia. Investigators have proposed several hypotheses for the pathogenesis of Dupuytren disease.
Al-Qattan hypothesizes that an individual with a genetic predisposition to develop Dupuytren disease experiences a second inciting event (ie, smoking, diabetes, trauma, alcoholism), resulting in microvascular ischemia.
The localized ischemia causes two events to take place in the palmar fascia:
(1) the conversion of adenosine triphosphate to hypoxanthine and
(2) the conversion of xanthine dehydrogenase to xanthine oxidase.
Al-Qattan hypothesizes that an individual with a genetic predisposition to develop Dupuytren disease experiences a second inciting event (ie, smoking, diabetes, trauma, alcoholism), resulting in microvascular ischemia.
The localized ischemia causes two events to take place in the palmar fascia:
(1) the conversion of adenosine triphosphate to hypoxanthine and
(2) the conversion of xanthine dehydrogenase to xanthine oxidase.
Xanthine oxidase acts as a catalyst for the oxidation of hypoxanthine to xanthine and uric acid; this conversion results in the production of free radicals.
Free radicals result in fibroblast proliferation and the production of numerous cytokines. Interleukin 1 (IL-1) is the most abundant cytokine in Dupuytren disease and, via its receptor, upregulates the production of transforming growth factor beta (TGF-beta), fibroblast growth factor, epidermal-derived growth factor, and platelet-derived growth factor.
This milieu of cytokines and growth factors results in the proliferation of fibroblasts and their differentiation into myofibroblasts (the primary cell type in Dupuytren disease).
Increased levels of nerve growth factor are present, which induce fibroblast transformation to myofibroblasts, especially during stages II-III. The splicing of fibronectin affects collagen binding. Platelet activation produces lysophosphatidic acid (LPA). LPA is a signaling molecule for cell proliferation and myofibroblast contraction.
After binding to its receptor on myofibroblasts, LPA leads to a decrease in cyclic adenosine monophosphate and an increase in intracellular calcium levels. These events mediate smooth muscle contraction of the myofibrils within the myofibroblast. Normal palmar fascia is primarily composed of type I collagen; Dupuytren disease is associated with an increase in type III collagen.
Genetic factors
Furthermore, DNA microarray analysis has demonstrated that the gene MafB is up-regulated in Dupuytren cord tissue. MafB is involved in tissue development and cellular differentiation.
Further support for a genetic link was provided by Al-Qattan, who described a maternally transmitted inheritance within the mitochondrial genome in 90% of patients. The defective mitochondria generate high levels of free radicals and defective apoptosis and are therefore directly related to disease pathogenesis
Others believe that Dupuytren contracture has a multifactorial inheritance, similar to diabetes or hypertension.
Additional risk factors
Whether certain conditions represent independent risk factors for the development of Dupuytren contracture is unclear. A large, retrospective study by Loos and colleagues on 2919 hands on which surgery had been performed revealed no statistically significant evidence that the occurrence of Dupuytren contracture could be correlated with the presence of diabetes, with alcoholism, or with smoking.
Another report, however, found different results, noting an association between Dupuytren contracture and several conditions (eg, alcoholism, diabetes, epilepsy, pulmonary disease), as well as a link with smoking. [32] Nonetheless, even if such associations exist, no clear causal relationship has been established in the literature.
HLA-DRB1*15 and HLA-DR3 have been identified in numerous patients, suggesting an immunologic influence. Each confers about a 2-3 times relative risk for the development of Dupuytren disease. [33, 34] Most likely, an inciting disease or event in a genetically predisposed individual causes a cascade of events that may include processes that promote the formation of growth factors and free radicals that ultimately leads to abnormal fibroproliferation and the appearance of the characteristic Garrod nodule. Even when homeostasis is ultimately achieved and fibroblastic growth lessens, the pathologic nodule and cord remain.
Dupuytren Contracture
Epidemiology
Frequency
Dupuytren disease is common in the United States with a prevalence of 4%, reflecting immigration from Northern Europe. In Northern Europe the prevalence ranges from 4-39%. In Norwegian populations, 30% of males over the age of 60 years are affected. The incidence of Dupuytren disease for the British population in 2004 was calculated at 34.4 per 100,000 for men aged 40-84 years. [10] Australia has a reported prevalence of 28%; Spain’s reported prevalence is 19% prevalence in in men older than 60 years. [3] Sporadic cases are reported in Africa and Asia. [10]
Mortality/Morbidity
The effects of morbidity in Dupuytren contracture are generally limited to lifestyle changes. MCP and PIP joint contractures may interfere with activities of daily living and the nodules can be painful. Occasionally, Dupuytren contracture is associated with plantar fascial thickening (Ledderhose disease), involvement of the penis (Peyronie disease), or involvement of the knuckle pads (Garrod nodes). These associations tend to reflect more aggressive disease. [52] No mortality occurs from Dupuytren contracture.
Race
Racial variation in Dupuytren disease is as follows:
Dupuytren disease is most often found in Caucasians of Northern European descent.
The disease prevalence in Asians is 3% and usually involves the palm rather than the digits. Therefore, it is less likely to be clinically significant, and the incidence may be underreported.
Dupuytren disease has been reported in East Africa, Zimbabwe, and Tanzania. [7]
Dupuytren disease is uncommon among Indians (< 1%), Native Americans, and patients of Hispanic descent. [7]
Sex and age
Approximately 80% of affected individuals are male; this is consistent throughout all countries and races. The disease onset in males tends to occur in the fifth to sixth decade. Men tend to present a decade earlier than females. The disease course tends to be more rapid and severe in males and increases in incidence with advancing age. [44]
Dupuytren disease is rare in children younger than 10 years. Only eight histologically proven cases have been reported
History
Obtain a thorough medical history when evaluating a patient thought to have Dupuytren contracture.
Presenting symptoms typically include the following:
- Decreased range of motion
- Loss of dexterity
- Getting the hand “caught” when trying to place it in a pocket
Conditions possibly related to Dupuytren contracture include the following:
- Diabetes mellitus
- Alcohol abuse
- HIV infection
- Epilepsy
- Trauma
- Manual labor with vibratory exposure
- Cigarette smoking
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 is generally not symmetric in severity.
Physical Examination
Perform a thorough physical examination focusing on the involved extremity. A careful physical examination often confirms the diagnosis without the need for further tests.
Important points to assess include the following:
1. Firm nodules that may be tender to palpation: The nodules are closely adherent to the skin; movement of the nodule with finger motion suggests an association with the tendon and not Dupuytren contracture.
- Painless cords proximal to the nodules
- Skin blanching upon active finger extension
- Atrophic grooves or pits in the skin: These represent adherence to the underlying fascia.
- Tender knuckle pads over the dorsal aspect of the PIPs (Garrod nodes): These occur in 44-54% of patients and suggest more aggressive disease.
- Plantar fascia involvement, known as Ledderhose disease (6-31%): This can indicate more severe disease.
- Presence of MCP and PIP joint contractures: Objectively measure and record the degree of flexion contracture and assess for compensatory DIP joint hyperextension or contracture.
- Hueston table top test: If the patient is unable to lay the palm flat on a tabletop, the findings are considered positive.
Work-up
No routine diagnostic laboratory studies apply to this disorder. However, diabetes mellitus has been associated with Dupuytren contracture. A fasting blood glucose level should be obtained if diabetes mellitus is suggested by the patient’s clinical history and physical examination findings.
No routine radiographs are necessary, but ultrasonography can demonstrate thickening of the palmar fascia, as well as the presence of a nodule. In addition, ultrasonography of a thickened cord may be useful prior to intralesional injections so that the underlying tendon can be identified and avoided during the injection.
Initial Approach/Treatment
Observation
This is appropriate for patients with unchanging, painless Dupuytren disease with minimal contracture and no functional impairment. [57] Patients with mild Dupuytren disease can be monitored on an infrequent basis via a brief follow-up visit every 6-12 months. In addition to accurate measurement of the progression of the contractures, the follow-up also provides an opportunity to elicit a history of any functional deficits. Further, these visits allow assessment and discussion of the need for surgical referral.
Physical and occupational therapy
Stretching with the application of heat and ultrasonographic waves may be helpful in the early stages of Dupuytren contracture. The physical therapist also may recommend that the patient wear a custom splint or brace to stretch the fingers further. Range of motion (ROM) exercises should be performed several times a day. If the patient undergoes surgical correction of the contracture, physical therapy often is involved following the procedure. The postsurgical program consists of wound care, massage, passive stretching, active ROM exercises, and splinting.
Through a course of occupational therapy, the patient may learn adaptive techniques and begin to use assistive devices that enhance functional abilities. For example, adaptive equipment can help a patient to open jars, despite contractures.
Corticosteroid injection
Intralesional triamcinolone acetonide (Kenalog-40) injections of 40 mg/mL have yielded subjective improvement in the size of Dupuytren nodules in some patients. Ketchum argues that early treatment of a nodule with an intralesional steroid injection, before the development of joint contracture (particularly PIP joint involvement), can interrupt the inflammatory process and thus the progression of disease. [59]
However, corticosteroids are associated with a high risk of complications, including fat atrophy and skin discoloration. [57] In addition, intralesional injection of corticosteroids can result in tendon rupture.
Later treatment
- Percutaneous needle fasciotomy/closed fasciotomy
Percutaneous needle fasciotomy (PNF) is a minimally invasive treatment that is usually performed as an office procedure under local anesthesia. It involves multiple puncture sites and sectioning of the Dupuytren cord using the bevel of a needle.
Needle fasciotomy may be an effective initial intervention in the treatment of Dupuytren contracture either alone or as a first step to subsequent procedures such as repeated fasciotomy, fasciectomy, or CCH injection.
- Fasciectomy
i. Regional (or selective) fasciectomy
This involves excising only the fascia that is grossly affected (eg. in the palm, pretendinous cords and involved natatory ligaments; in the fingers, only those structures that are visibly affected). Although the disease process clearly extends into clinically normal palmar fascia, this approach has proven successful in correcting MCP joint contractures and some PIP contractures and carries an acceptably low morbidity rate.
Areas not treated may develop disease. This method is commonly used to treat primary and recurrent disease. Skin incisions may be transverse, longitudinal, or diagonal/zigzag (eg, Z-plasty, Y-V-plasty, Bruner-type zigzag incision). Local advancement flaps, including an ulnar-based skin flap [86] and palmar inter-metacarpal flap [87] have been described.
In a study of selective fasciectomy, Hueston concluded that this procedure does not prevent recurrence of Dupuytren disease but does allow correction of deformity with more rapid recovery of hand function.
ii. Extensive or radical fasciectomy
This involves excision of the entire palmar fascia, including tissue that appears grossly healthy (in an effort to prevent recurrence). Although this procedure is not commonly performed today, it results in a relatively low recurrence rate of about 11%. [89] It does have an increased risk of morbidity postoperatively, including hematoma in 14% of cases and nerve irritation or damage in 6%. Patients are also prone to prolonged postoperative edema and stiffness. One study concluded that total aponeurectomy was most appropriate for stage 2 disease.
