Metalloproteinases and Dupuytren's

A better understanding of the biology of metalloproteinases may lead to new treatment options for Dupuytren's. Metalloproteinases (MMPS) are a group of enzymes in our bodies which break down certain proteins, including collagen. MMPS are blocked by tissue inhibitors of metalloproteinases (TIMPS). MMPS and TIMPS balance each other: imbalances have been implicated in conditions of excess collagen, as seen in Dupuytren's, or inadequate collagen leading to rotator cuff tears. The article "Metalloproteinases and their inhibitors—diagnostic and therapeutic opportunities in orthopedics" (full text: http://www.dupuytrenfoundation.org/DupPDFs/2009_Pasternak.pdf) is a clearly written and thorough review of the topic and its implications for Dupuytren's and other conditions. MMPs are involved in the biology of inflammation and wound healing, which overlaps the cell biology of Dupuytren's. The authors note "In view of the strong hereditary component and a predilection for men in Dupuytren’s disease, it is interesting to note that TIMP-1 is located on the X-chromosome." It may not be that a man's Y chromosome puts him at special risk, but that a woman's X chromosome offers her special protection. In addition to involvement with Dupuytren's, MMPs and TIMPs appear to play key roles in unrelated disorders including arthritis, degenerative disk disease, tendinitis, fracture healing and other conditions. Inroads made in understanding their role in Dupuytren's are likely to benefit people suffering from other conditions - an added incentive to work for a cure.

Stony Brook Dupuytren Symposium

What a year for Dupuytren's! Xiaflex is FDA approved, the 2010 International Symposium on Dupuytren's Disease http://www.DupuytrenSymposium.com is coming up May 22,23 in Miami, and now Stony Brook University Medical Center Department Of Orthopaedics has announced its Dupuytren’s Disease Symposium Saturday, April 17th, 2010 in Stony Brook, New York. The program flier is http://sbumc.informatics.sunysb.edu/sbumcfiles/Dupuytrens%20brochure.pdf. The program lists an international faculty and reviews Dupuytren's biology in addition to a spectrum of management options to straighten fingers bent by Dupuytren's. The Stony Brook Symposium will be a perfect complement to the Miami Symposium's goals of presenting new research and establishing a coalition to work toward a cure for Dupuytren's disease and related conditions.

Radiotherapy for Dupuytren's

Radiation treatment for Dupuytren's disease has been performed since the advent of therapeutic radiation treatment. The effectiveness of radiation is reported as a preventative measure for early disease to prevent progression, not as a treatment for contracture. Although not widely embraced in the United States, there is a large European experience with radiotherapy of Dupuytren's Disease. Literature access is restricted by the unfortunate fact that reports have been published in journals whose publishers continue to lag behind the trend to provide open internet access access to their publications. Medline abstracts are available and a Medline search this month of Radiotherapy for Dupuytren's is available here (full text: http://www.dupuytrenfoundation.org/DupPDFs/2010_Medline_XRT.pdf). These articles report a benefit of radiotherapy in early stage Dupuytren's in slowing the progress of contracture, a low complication rate, no reports of radiation induced cancer and no interference with later surgery for those who failed radiation and developed progressive contractures. These reports must be reviewed with the knowledge of anecdotal reports in surgical texts of significant complications from radiation for Dupuytren's. The truth lies somewhere in between. The difficulty with interpreting reports of any treatment of Dupuytren's is lack of information regarding additional risk factors: The biologic aggressiveness of Dupuytren's, progression and recurrence, is predictably and significantly affected by family history, presence of knuckle pads, Ledderhose, Peyronie's or frozen shoulder, age, age of onset, bilaterality and number of digits involved, nodularity of disease, skin involvement, certain medications, alcohol intake and other risk factors. The true effectiveness of any preventative treatment must take these types of factors into account to have real validity. This is why a standard approach to documentation and a global collaborative effort to generate and analyze large amounts of data is important to make progress in developing better treatment options for Dupuytren's and related conditions.

Dupuytren's and other fibroses

Dupuytren's is a fibrotic disease, a fibrosis - one of many. Fibrosis, as a word, sounds exotic, but it is really just the medical name for scar. Although injuries come in many forms and can involve any structure, our bodies have a limited repertoire for reacting to injuries. The universal poultice our body's healing process puts into areas of injury is collagen. A scar is mostly collagen. When a broken bone heals, the body first glues the break together with collagen; calcium crystals form in this glue, eventually turning it into bone. Collagen is stuff we are made of: anything solid or mechanically important in our bodies, even bone, is mostly made of collagen. Collagen needed for us to live; collagen is good, but in the right place and in the right amount. Fibroses show that even for collagen, there can be too much of a good thing. If collagen is like the bricks making up the house in which our cells live, fibrosis is like adding extra bricks inside the house: too many bricks and the house stops being livable. Fibrosis may affect a specific location, as in Dupuytren's, or may diffusely involve an entire organ, as in pulmonary fibrosis. Why do fibroses occur? This is the question we need to investigate on the quest to find a cure for Dupuytren's. Drugs play a part in certain fibroses. In "Drug-Induced Localized Systemic Scleroses" (full text: http://www.dupuytrenfoundation.org/DupPDFs/1981_Graham_1601.pdf), the role of drugs and fibroses, including Dupuytren's, is explored.

Reimbursement for Needle Aponeurotomy and for Xiaflex

Needle aponeurotomy (NA) is referred to as percutaneous fasciotomy in the AMA Common Procedural Terminology (CPT) listing. CPT codes are the standard language used by health care providers and the insurance industry regarding reimbursement. Several years ago, Blue Cross of Massachusetts quietly removed the code for NA (26040) from their list of reimbursed procedures, as if it didn't exist. It's baffling - the procedure code has been part of the AMA coding system for the duration of the system, and is an established Medicare reimbursed code.

Given the progressively slippery changes of the unregulated business practices of the private health insurance industry over the last 30 years, this may be part of a larger strategy of benefit denial - quietly removing codes for services which, because they are uncommonly used, won't generate a large public outcry. The code removal may have been triggered by the fact that 26040 was almost never filed as a claim before NA came to the US in 2003. In the same way that policyholders risk being dropped when they file a claim, the code may have been dropped because it began generating a cost. Whatever the reason, this is part of a larger trend, as reflected by a 2009 survey of the members of the American Society for Surgery of the Hand regarding insurance denials (full text: http://www.dupuytrenfoundation.org/DupPDFs/2009_Insurer_Payments_Survey_Summary_100609.pdf)

NA is far less expensive than open surgery: it would seem profitable for the insurance industry to push patients to have it rather than deny coverage for it, but the opposite is happening. Why? A simple, logical explanation is that there are many people who will not consider open surgery for Dupuytren's, but would consider NA. If the insurance analysis is that the number of open surgery claims is stable but the number of NA claims is rising, this would be interpreted as increased utilization rather than cost savings - an incentive to not pay for NA rather than to support it. From the insurance industry perspective, the best possible outcome is for you to pay for your premiums and then for you to also pay for all of your medical expenses. Time will tell if the same strategy of denial will also affect reimbursement for Collagenase/Xiaflex.

Dupuytren's: it's not just the fascia.

Dupuytren's contracture is a local manifestation of a systemic process, and although the palmar fascia is the usual focus, what happens in the hand is a regional process, affecting the skin and the fatty layer under the skin as well as the fascia: it appears to be something which brews between the skin and the fascia, not just in the fascia. This concept and its consequences were eloquently reviewed by the late, great John Hueston in "The role of the skin in Dupuytren's disease" (full text: http://www.dupuytrenfoundation.org/DupPDFs/1985_Hueston_1125.pdf). His observations regarding the anatomy ("A nodule is never found on the dorsal aspect of a palmar aponeurosis..."), the biology ("...obsession with the collagenous structure of the palmar tissues is at present being replaced by the more logical study of the cellular origins..."), and the logic of dermofasciectomy and full thickness skin graft for aggressive or recurrent Dupuytren's are even more relevant today than when the article was published 25 years ago.

Alcohol and Dupuytren's

Is there a relationship between drinking alcoholic beverages and the chance of having Dupuytren's? This has been debated for years. The answer? Yes, according to the report "Dupuytren's contracture and alcohol" (full text: http://www.dupuytrenfoundation.org/DupPDFs/1986_Bradlow_1148.pdf). The authors reviewed 143 patients with and without Dupuytren's, checked their self described drinking patterns as well as the blood tests which are abnormal in heavy drinkers, and concluded that, at least in men, regular heavy alcohol consumption, measured either by history or blood tests, was associated with a higher risk of Dupuytren's contracture. Why? There are many possible biological reasons, including the chemical effects of alcohol (or its byproducts) and the effect of alcoholic liver disease on the metabolism. On the bright side, light or moderate alcohol consumption - meaning not enough to show liver damage - is apparently not a risk factor for the development of Dupuytren's disease. Whew.

Dupuytren Symposium Program Listing

The 2010 International Symposium on Dupuytren's Disease http://dupuytrensymposium.com is one step closer. The faculty http://dupuytrensymposium.com/presenters.html and program syllabus  http://dupuytrensymposium.com/program.html are now available for review. This continues the collaboration to find a cure.

Is Dupuytren's an immune problem?

Is Dupuytren's an autoimmune or an allergic condition? In some fibrotic diseases, such as endomyocardial fibrosis, tissues show activity of eosinphils. Eosinophils are normally found in small numbers in the bloodstream. They are part of the immune system and are abnormally involved in some medical conditions such as asthma. Eosinophils are filled with little bags of chemicals, called granules, and in a prepared slide under the microscope, the granules stand out as beautiful little red jewels. Their pretty appearance is deceiving: some granules are filled with toxic compounds which are released to kill invading organisms. These toxins can also kill normal cells and cause scarring and fibrosis. Researchers analyzed tissue specimens for a possible link between eosinophils and fibrosis in several conditions, including Dupuytren's, and reported their findings in "Tissue Eosinophilia and Eosinophil Degranulation in Syndromes Associated with Fibrosis" (full text: http://www.dupuytrenfoundation.org/DupPDFs/1992_Noguchi_1104.pdf). They found strong evidence for eosinophil involvement in retroperitoneal fibrosis, sclerosing mediastinitis, and sclerosing cholangitis, but none in Dupuytren's. One less lead to investigate in the quest to find a cure for Dupuytren's.

Similar genes found in Dupuytren's and Peyronie's

Dupuytren's and Peyronie's disease are believed to be related, to share a common genetic starting point. This has been an assumption, not hard fact: the genetic starting points of these conditions are not yet known, much less known to be the same. Doctors have been wrong on these issues in the past: in the 1800's, it was an accepted "fact" that Dupuytren's and gout were related. They are not: the only relationship is demographic overlap. We now have better tools to find genetic similarities of Dupuytren's Disease (DD) and Peyronie's Disease (PD). All normal body processes are regulated and balanced by genetically controlled feedback loops: genes are upregulated (turned on) or downregulated (turned off) to maintain balance. DD and PD are the end effects of a broken feedback loop: an on switch is stuck in the on position, an off switch is stuck off, or both. One way to study up and down regulation is to use reverse transcriptase. Here's how it works. Genes are different molecules strung together into huge DNA molecules. When a gene is upregulated (turned on), it makes RNA molecules, which are like small, mirror images of itself. RNA carries orders from the boss DNA to control the rest of the cell. Reverse transcriptase is a laboratory technique which reverses this process, making DNA mirror images of RNA taken from living cells to find what genes the RNA came from - what genes are upregulated. In this study "Comparison of gene expression profiles between Peyronie’s disease and Dupuytren’s contracture" (full text: http://www.dupuytrenfoundation.org/DupPDFs/2004_Qian_1570.pdf), this technique was used to identify upregulated and downregulated genes in Peyronie's, Dupuytren's and normal tissues. The result? Yes, DD and PD appear to be genetically related. The list of identified genes and their actions is reviewed in the article. More pieces of the puzzle, more steps closer to a cure.

Xiaflex Pricing

Auxilium has moved closer to product availability of Xiaflex collagenase injection for the treatment of Dupuytren's contracture by announcing the wholesale drug price: $3250.00 for a single treatment dose. For those who think that this seems high, consider this in perspective. There are many categories of pharmaceutical products. Most commonly available pharmaceuticals are classified as "small molecule" drugs: organic compounds "small" enough to be able to be absorbed directly into cells. Some small molecule drugs, such as morphine, penicillin, aspirin and cortisone have been used for years; others are new, like the cancer drug Gleevec. In contrast, "biologics" are complex large molecule organic compounds. Biologics are much more difficult (expensive) to purify than small molecule drugs. They are often produced using costly recombinant DNA technology. Biologics include Enbrel for rheumatoid arthritis, Botox for spasticity, and now Xiaflex for Dupuytren's contracture. Each of these biologics reduces the need for surgery for a specific condition. They are expensive, but cheaper than surgery. Who is going to pay for Xiaflex? The same sources that pay for surgery: private insurance, Medicare, or, if neither is available, the patient. The paperwork will be different, but the process will be quite similar. Auxilium has a patient information site http://dealingwithdd.com and physicians can call 1-877-663-0412 to get more information. Xiaflex cost should be compared not just to open surgery, which is widely available but more expensive, but also to needle aponeurotomy, which is less expensive than Xiaflex but available at fewer centers. Confusing? Somewhat, but it's great to have several options for treatment while we continue work to develop a true cure.

Dupuytren's Demographic Data

While researchers look through the microscope at the cellular biology of Dupuytren's, surgeons look for clues using the fish eye lens of demographic observations. Who is at risk? What family, lifestyle, medication and medical condition issues affect the incidence and magnitude of Dupuytren's? There is a long history of these questions and observations. A typical report from over 50 years ago reviews issues which are still worth considering: "Dupuytren's Contracture" (full text: http://www.dupuytrenfoundation.org/DupPDFs/1948_Gordon_1409.pdf) outlines the contribution of family history, occupation, location of involvement, gender and age to Dupuytren's, as well as descriptions of sympathetic dystrophy mimicking Dupuytren's ("acute form"), complications of surgery and difficulties with therapy after surgery. Time has passed, but so much is the same, reminding us that none of these issues will change until we find a cure.

RNA, Growth Factors and Dupuytren's

Sorting out the genetic basis of Dupuytren's is not simply a matter of finding out which genes are involved. The goal is to understand the biochemistry of exactly what these specific genes do to either start or fail to stop the process of Dupuytren's. Cell biology is always a domino like set of events with many steps. The DNA molecules in a cell's genes act as a template to make messenger RNA (mRNA), which travels from the cell's nucleus to its protein manufacturing factories (ribosomes), where the mRNA then acts as a template to string amino acids together to make proteins. Our bodies use some proteins, like collagen, as structural building material; other proteins, called cytokines, are used as currency of communication between cells, directing cells what to do. In this study, "Abnormal growth factor and cytokine expression in Dupuytren's contracture" (full text: http://www.dupuytrenfoundation.org/DupPDFs/1993_Baird_1442.pdf), researchers analyzed the cytokines produced by mRNA in Dupuytren's tissue, and found abnormal activity of interleukin-1a, interleukin-1ß, transforming growth factor ß and basic fibroblast growth factor. This approach, linking genes with proteins, brings us a step closer to solving the puzzle of a cure.

Dupuytren's Diathesis

What is Dupuytren's Diathesis? Diathesis is a medical term meaning tendency toward a condition. One way of describing a person with Dupuytren's diathesis is that they have more of whatever Dupuytren's is. Diathesis usually means more aggressive Dupuytren's: earlier age of onset; more fingers involved; more often bilateral; faster progression; more recurrence problems. The hallmark is developing more than one member of the Dupuytren family: Dupuytren's; knuckle pads; Ledderhose; Peyronie's; frozen shoulder. More conditions means more aggressive biology. People with Dupuytren's diathesis are more likely to have ancestors with Dupuytren's and are more likely to pass Dupuytren's on to their children than people with only Dupuytren's. In this article, "Dupuytren's Diathesis: A Case Report" (full text: http://www.dupuytrenfoundation.org/DupPDFs/1964_Lettin.pdf), the difficulties experienced by a patient with Dupuytren's diathesis are described, as well as complcations from both surgery and radiation treatment. Diathesis is a persistent reminder that Dupuytren's is a systemic disorder which has many forms, and that we need to continue work to find a biological cure.

Needle Aponeurotomy and Xiaflex compared

Xiaflex (Collagenase) has finally been approved by the FDA for the treatment of Dupuytren's contracture. When work began on the development of collagenase to treat Dupuytren's contracture, the bar was pretty low: anything better than fasciectomy in terms of either safety or efficacy would be a great advance. No other treatment options were available in the United States. However, during the time that research was being performed on collagenase, needle aponeurotomy was introduced into the US and has gained some popularity. This changes the equation for collagenase - it's no longer the only alternative to fasciectomy. How will this play out? Read this comparison of needle aponeurotomy and Xiaflex (full text: http://handcenter.org/newfile20.htm) and decide for yourself.

Growing bent fingers straight

Two things are needed for people dealing with Dupuytren's: a way to reverse or restore fingers back to their natural state and a way to prevent progression/recurrence. For the former, progress is being made; the latter remains the elusive goal of a cure. Dupuytren's is a shrinking process. The ideal treatment would be to reverse this: a growing process. Technically, this can be done by slowly stretching the tissues with a mechanical device: tissue growth can be initiated and guided by specific mechanical forces. The Digit Widget is the device most most frequently used to stretch and straighten proximal interphalangeal joint contractures due to Dupuytren's. The technical manual for this, "Reversing PIP Joint Contractures: Applicability of the Digit Widget External Fixation System" (full text: http://www.dupuytrenfoundation.org/DupPDFs/2002_Agee.pdf) shows how the complicated and precise anatomy of the proximal interphalangeal joint makes this a formidable undertaking. As tricky as this is, it still pales in comparison to the hurdles of molecular biology which must be achieved to find a cure.

Cellular biomechanics are the key to Dupuytren's.

Dupuytren's is truly a biomechanical process, and the ultimate process has to do with the way that fibroblasts and myofibroblasts attach to each other and physically attach to strands of collagen and other components of the tissue matrix which surrounds them. An investigation into the complex junction of living cells, strings of proteins and mechanical/chemical interactions is reported in the article "Physical State of the Extracellular Matrix Regulates the Structure and Molecular Composition of Cell-Matrix Adhesions" (full text: http://www.dupuytrenfoundation.org/DupPDFs/2000_Katz.pdf). The topic was touched on in a previous blog http://dupuytrenfoundation.blogspot.com/2009/11/stretching-may-provoke-dupuytrens.html and represents the type of research which needs to be promoted to find biologic treatment options for Dupuytren's and related conditions.

Fasciectomy: Unsafe at any Speed?

Fasciectomy, invented by Goyrand just a few years after Dupuytren's initial demonstration of open fasciotomy, has been the main treatment option for Dupuytren's for nearly 200 years. There have been many refinements, but the central theme of removing fascia is unchanged. With so much time and experience, one might assume that all of the wrinkles had been ironed out. Not so. Fasciectomy has inherent, unavoidable dangers even in experienced hands because of both technical difficulty and biologic reaction. In this recent report, "Surgical Complications Associated With Fasciectomy for Dupuytren's Disease: A 20-Year Review of the English Literature" (full text: http://www.dupuytrenfoundation.org/DupPDFs/2010_Denkler.pdf), the numbers are notable. On the average, one out of six fasciectomy patients experience a major complication; more if the procedure is for recurrent disease; even more if one asks the patients rather than the surgeons. This risk is hard to justify for the treatment of a benign condition. We need better treatment options to straighten out bent fingers, but also to prevent contractures from progressing or recurring.

Frozen Shoulder, Dupuytren's Cousin

Dupuytren's contracture and frozen shoulder share similar biology and many people with one condition will eventually develop the other. Frozen shoulder differs from Dupuytren's in that it is typically a painful condition with rapid onset, is more common in women and usually runs a limited course. It is similar in terms of its cellular biochemistry and in that it may result in permanent stiffness. Some of the differences may be due to the anatomic differences: the shoulder capsule physically moves more than the palmar fascia; there are sensory nerves in the shoulder capsule but not the palmar fascia. The topic of frozen shoulder is reviewed further in this clearly written review (full text: http://www.dupuytrenfoundation.org/DupPDFs/2005_Dias.pdf)

Flare reaction after fasciectomy for Dupuytren's

Flare reaction refers to a disproportionate degree of swelling, pain and stiffness developing after surgery for Dupuytren's contracture. Although commonly known, there is relatively little published on this. Flare shares some features with reflex sympathetic dystrophy, another poorly understood condition which is seen more often after Dupuytren's surgery than other hand procedures. Flare reaction appears to be triggered by some combination of skin incisions and mechanical tension on the skin: it does not occur after needle aponeurotomy when a minimum number of portals are used. Flare reaction greatly prolongs recovery and may result in permanent stiffness of the hand. This article documents a case of flare reaction after fasciectomy for Dupuytren's and reviews the difficult issues it presents: (full text: http://www.dupuytrenfoundation.org/DupPDFs/2008_Fournier_1045.pdf)

Dupuytren's and Associated Conditions

Dupuytren's is associated with three conditions, Ledderhose, Peyronie's and frozen shoulder. These all share a similar biology at a cellular level. Dupuytren's is also associated with other conditions, such as diabetes, alcoholism, epilepsy, advanced HIV for reasons which are less clear. Is Dupuytren's a risk factor for some of these other health issues or is it the other way around? This article reviews conditions associated with Dupuytren's and some thoughts on these associations: (full text: http://www.dupuytrenfoundation.org/DupPDFs/2005_Hart_1609.pdf). Although not discussed in this review, smoking tobacco also increases the risk of developing Dupuytren's disease, as discussed and referenced in this review (full text: http://www.dupuytrenfoundation.org/DupPDFs/2004_Conrad.pdf).

Genes, enzymes and Dupuytren's: the alphabet name game.

A proteinase is an enzyme which breaks down proteins. Metalloproteinases (MPs) are proteinases with a molecular structure and function involves a metal atom, usually zinc. Matrix Metalloproteinases (MMPs) are MPs which act outside of cells, in the tissue matrix. Human collagenases are MMPs which break down different types of collagen. Membrane-type MMPs (MT-MMPs) are MMPs which are attached to cell membranes and protrude into the extracellular matrix. ADAMTS (A Disintegrin And Metalloproteinase with Thrombospondin Motifs) are another subgroup of MMPs. ADAMTs cut off or shed portions of proteins which protrude out of the cell wall, and are classified as sheddases (I am not making this up). TIMPs (Tissue inhibitors of Metalloproteinases) block the action of MMPs. This lecture handout outlines investigation of which genes relating to MMPs and ADAMTs are activated in osteoarthritis and Dupuytren's disease (full text: http://www.dupuytrenfoundation.org/DupPDFs/2007_Clark.pdf). In active Dupuytren's disease, five genes were involved: MMP13, which codes for collagenase 3 (breaks down type II collagen (in cartilage), and to a lesser extent types I and III collagen (in Dupuytren's cords); MMP14 codes for MMP-14, a MT-MMP collagenase which activates collagenase 3 and is activated by poor circulation; ADAMTS5, which codes for aggrecanase, an ADAMTS which breaks down cartilage; ADAMTS14, which is linked to procollagen processing; ADAMTS16, which codes for an enzyme whose function is unknown. More information on this is available here: (full text: http://www.dupuytrenfoundation.org/DupPDFs/2008_Murphy.pdf). Dupuytren's is somehow related to the way that all of these genes interact. Here's a simple question based on all of this: if Dupuytren's is related to not enough collagenase function, and zinc is needed for collagenase to function, and EDTA is an additive put in soda pop because it removes metals such as zinc, could drinking too much of your favorite carbonated beverage raise your risk for Dupuytren's?

LSD as a treatment for Dupuytren's?

There is one published report of Dupuytren's being cured, fingers suddenly straightened, under the influence of the psychedelic drug LSD (full text: http://www.dupuytrenfoundation.org/DupPDFs/1966_Solursh_1417.pdf). Is this true? Probably not. LSD is a serotonin antagonist, and other serotonin antagonist drugs, such as methysergide, have been shown to cause retroperitoneal and cardiac valve fibrosis. Based on this information, LSD might be exactly the wrong drug to take for other fibrotic conditions such as Dupuytren's. The search continues.

FDA approves Collagenase for Dupuytren's

Collagenase (Xiaflex) has been approved by the FDA for treatment of Dupuytren's contracture, after years of intensive laboratory and clinical trials. Collagenase enzymatic  fasciotomy is more similar to needle fasciotomy than to either open fasciotomy or fasciectomy in terms of rapid recovery and low complication rate. Compared to needle release, collagenase enzymatic fasciotomy should eventually be more widely available (because it is easier for surgeons to learn), takes less time to perform, but provokes more inflammation and will be more expensive. Auxilium's press release (full text: http://www.dupuytrenfoundation.org/DupPDFs/2010_Auxilium1.pdf) and physician prescribing information (full text: http://www.dupuytrenfoundation.org/DupPDFs/2010_Auxilium2.pdf) are now available. We live in exciting times for Dupuytren's because for nearly 200 years, there has been essentially one treatment option, surgery, but within the last few years, this has expanded to also include needle release, dynamic fixation and now enzymatic fasciotomy. This has led to greater awareness of Dupuytren's. It is now time to transform this awareness into support for efforts to develop an actual cure.

Dupuytren's Genes

The hunt is on for the genetic basis of Dupuytren's. A interesting analysis of the chromosome patterns found in Dupuytren's tissue found a variety of genetic abnormalities and the unexpected finding that these variations were not found in the skin but were seen in areas of palmar fascia not usually involved with Dupuytren's. (full text: http://www.dupuytrenfoundation.org/DupPDFs/1988_Wurster-Hill_1091.pdf). Twenty years after this report, the hunt is still on with more sophisticated equipment, identification of involved genes closer but still elusive: http://dupuytrenfoundation.blogspot.com/2009/11/gene-expression-in-dupuytrens.html. Still, so many questions: is it determined by one or several genes? If, as widely believed, the trait is a dominant gene, why is Dupuytren's more common in people with blue eyes, the result of a recessive gene? Does the genetic effect only involve the palmar fascia or all fascia? Dupuytren's skips generations and often appears with no family history: is it a common spontaneous mutation, and if so, is it more common in those born to older parents? Some day, these questions will be answered. With persistence, some day, there will be a cure.

Luck and Dupuytren's

Needle aponeurotomy for Dupuytren's is not that new. It's a new twist on the very first operation described for Dupuytren's, percutaneous fasciotomy, which was performed by Cooper years before Dupuytren's famous presentation. Adams wrote extensively about his results with percutaneous fasciotomy for Dupuytren's in the late 1800s. Before Lermusiaux began using a needle for percutaneous fasciotomy and calling it needle aponeurotomy, the last doctor to have much experience with the technique was Vernon Luck, who used his own "Luck Fasciotome", a tiny knife made in his machine shop, to perform percutaneous fasciotomy. Luck reported his concept of the biology of Dupuytren's along with his experience with his technique, and it's an interesting read. (full text: http://www.dupuytrenfoundation.org/DupPDFs/1959_Luck_1074.pdf)