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Recent Advances in Understanding Dupuytren Disease
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Posted on: 11/20/2008
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New understanding of the biochemical basis of Dupuytren disease may help explain complications that often occur after surgery for this condition. In this report, surgeons from Georgetown University Hospital in Washington, D.C. bring us up-to-date on the recent research findings related to Dupuytrens.
Dupuytren's contracture is a fairly common disorder of the fingers. The condition usually shows up as a thick nodule (knob) or a short cord in the palm of the hand, just below the ring finger. More nodules form, and the tissues thicken and shorten until the finger cannot be fully straightened. Dupuytren's contracture usually affects only the ring and little finger. The contracture spreads to the joints of the finger, which can become permanently immobilized.
One or both hands can be affected. Although the exact cause is unknown, it occurs most often in middle-aged, white men. It is genetic in nature, meaning it runs in families. Dupuytren disease is seven times more common in men than women. It is more common in men of Scandinavian, Irish, or Eastern European ancestry. The disorder may occur suddenly. More often, it progresses slowly over a period of years. The disease usually doesn't cause symptoms until after the age of 40.
There are some other known risk factors for this disease. These include diabetes, alcohol abuse, and tobacco use. Trauma from injury or vibration during manual labor can also increase the chances of developing Dupuytrens. The natural course of the disease is unpredictable. Some people have a mild case that doesn't cause problems. Others progress to severe contracture preventing proper use of the hand.
Surgery to release the soft tissues (fasciectomy) and/or remove the contracted fascia (connective tissue) (fasciotomy) is the main treatment approach. The procedure is done through the skin and is called percutaneous needle fasciectomy/fasciotomy (PNF).
But because the problem is genetic, it's likely to recur despite treatment. In fact, up to 65 per cent of the time, the fingers start to stiffen up again soon after the operation. Sometimes the trauma of the surgery makes the problem worse instead of better.
The younger the patient is when the disease occurs, the more likely the problem will repeat itself over time. Results from surgery aren't always perfect. Complications such as stiffness, infections, and delayed healing with loss of hand function can occur. There can be permanent problems if the nerves or blood vessels are damaged during surgery.
New information about the molecular basis of Dupuytrens has caused scientists to take a second look at this condition. The goal is to improve treatment results and reduce the incidence and severity of complications. So what are the latest biomolecular discoveries associated with Dupuytrens?
Labratory examination of tissue has shown that fibroblast growth factor (FGF), interleukin-1 (IL-1), and epidermal growth factor(EGF) are increased in the affected tissue. At the same time, transforming growth factor-alpha (TGF-alpha) and platelet derived growth factor are found more often in these same tissues.
With increased collagen deposits in the tissue, it's likely that enzymes that get collagen tissue growing and collagen inhibitors that keep collagen from overgrowing are part of the picture. Genes for the regulation of collagen are not in balance in this condition. Gene products such as metalloproteinases (MMPs) seem to have a role in the abnormal formation, remodeling, and shortenng of the collagen matrix in the tendons.
Once scientists figure out which gene products are involved, they may be able to target the affected genes that are dysregulated. Treatment will be directed to stop the formation of excess collagen in Dupuytren disease. Investigations are underway now injecting collagenase into the affected tissue. Collagenases are enzymes that break the peptide bonds in collagen. The injected collagenase breaks down the cords that are causing the tendon contractures in Dupuytren disease.
There are a few studies done so far using collagenase injections for this condition. The short-term results (up to two years) have been very favorable with a low rate of complications or recurrence. The number of patients studied so far using this approach has been fairly limited. But the results are encouraging enough to continue trying this nonsurgical treatment. The major problems have been reactions to the injections such as pain, swelling, and brusing. But these responses were mild and went away after 10 to 14 days.
The authors conclude by saying that the current surgical approach to Dupuytrens is being reviewed and reevaluated. The results with percutaneous release or removal of the fascia are less than satisfactory with high rates of disease recurrrence. Newer, less invasive gene-specific targeted therapy may be the gold standard of the future. Studies to understand the underlying biochemical and molecular processes behind Dupuytrens will help pave the way for more effective treatment with long lasting results (if not cure).
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References:
Ryan J. Caufield, and Scott G. Edwards, MD. Dupuytren Disease: An Update on Recent Literature. In Cuurent Orthopaedic Practice. September/October 2008. Vol. 19. No. 5. Pp. 499-502.
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