Dupuytren Foundation 2010 Report

It's been a busy year behind the scenes for the Dupuytren Foundation - see what we've been up to at http://conta.cc/hV1lEy

2010 Dupuytren's Symposium Screensaver. Mysterious, like Dupuytren's

Produced for the 2010 Miami Dupuytren Symposium with Electric Sheep and Wax Audio, this musical animation provides a background to contemplate new approaches to find a cure for Dupuytren's. http://www.youtube.com/watch?v=KOrWEYWl4fA

Miami Dupuytren Symposium spurs new research: Report from Dupuytren's Day at the Deutsche Gesellschaft für Handchirurgiethe (German Society for Surgery of the Hand - DGH)

Dr Wolfgang Wach reports from the DGH, Oct 7 Dupuytren Program: "I attended the Dupuytren’s day at the Nuremberg conference of German hand surgeons and the Miami Dupuytren Symposium was pretty well covered there. Bernhard Lukas gave a review of the Miami conference and the current issue of the German hand surgeons journal which was distributed at the conference also contained a 3 page summary by Bernhard Lukas and Albrecht Meinel of the Miami conference. Lawrence Hurst presented collagenase. Albrecht Meinel presented an extended version of his Miami anatomy and his splinting papers, Bernhard Lukas presented his surgery paper, Holger Erne and Bernhard Lukas gave papers on NA, Ilse Degreef presented a summary of her papers, Hans Hennies presented an update on his genomics study and mentioned that, as result of the Miami Dupuytren Symposium, the UK, the Netherlands, and the German genomics study started cooperating and are exchanging samples. Great! I also gave a little patient talk.".
The full conference program can be downloaded at http://www.dgh-kongress.de/dgh2010/Hauptprogramm_DGH2010.pdf. The DGH web site is http://www.dg-h.de. This new joint effort of researchers is a realization of a goal of the Dupuytren Foundation: to spur global collaboration to develop better treatment options for Dupuytren's; to find a cure. It is happening.

Swimming the English Channel to Support Dupuytren's Research

Surgeons and surgeons in training brave the English Channel to raise money to support hand surgery research: http://www.oxfordmail.co.uk/news/yourtown/oxford/8441861.Swimming_medics_show_surgical_spirit/ Cold! I mean ...How cool is that? Good work!

Video: I was a Teenage Myofibroblast (and I loved it!)

Before becoming the villain in Dupuytren's, the myofibroblast was really not a bad cell. What happened? What caused the change? Could it happen to you? Professor Sem Phan, Department of Pathology, University of Michigan explains almost everything in this presentation of "Mechanisms of Myofibroblast Differentiation":
http://www.youtube.com/user/DupuytrenFoundation#p/u/0/dsPwSUDrz1Y

Funding for these and other Miami Dupuytren Symposium videos at http://dupuytrensymposium.com/program.html, is provided by the Dupuytren Foundation. Support the Dupuytren Foundation with an online donation: http://CureDup.com.

The Secret Life of Myofibroblasts: Dr. Boris Hinz reveals all!

Boris Hinz PhD, University of Toronto, Ontario, CA presents "Fundamental aspects of myofibroblast contraction." and explains how the process is both simple and complex. How do these little cells do such big things? More importantly, what steps in the process go wrong to result in Dupuytren's and what can be done to safely and simply correct this? Watch the video and see: http://www.youtube.com/user/DupuytrenFoundation#p/u/0/fvmRS3OiWic

Funding for these and other Miami Dupuytren Symposium videos at http://dupuytrensymposium.com/program.html, is provided by the Dupuytren Foundation. Support the Dupuytren Foundation with an online donation: http://CureDup.com.

Dupuytren's vs. Burns! Video: Dr. Paul Zidel at the 2010 Miami Dupuytren Symposium

Dr. Paul Zidel, Chief, Hand Surgery, Maricopa Medical Center, Phoenix, Arizona, presents a thought provoking comparison of two different yet similar conditions in "Dupuytren's versus burn scar contracture"
http://www.youtube.com/user/DupuytrenFoundation#p/u/0/uR5OcoIKfOI
Hypertrophic scars, Ledderhose disease, burn scars, keloid scars, desmoid tumors, pulmonary fibrosis, arteriosclerosis and other abnormal fibrosing conditions share some of the same complex biology as Dupuytren's. Answers found for one condition may apply to others - there are many stones yet unturned in the path to find a cure for Dupuytren's. Support the effort at http://CureDup.com

Video: Professor Millesi at the Miami Dupuytren's Symposium

Professor Hanno Millesi of the Millesi Center in Vienna, chairman of the 1983 Dupuytren's Meeting in Vienna, presents "Changes of the visco-elastic properties of the palmar fascia as pathogenetic basis of Dupuytren's Disease": http://www.youtube.com/user/DupuytrenFoundation#p/u/0/vRc9XFBOVTk. The more one investigates, the deeper the mystery of Dupuytren's becomes. The legendary Dr. Millesi explores the chicken and egg aspect of the mechanics of Dupuytren's.
These and other videos are archived at http://dupuytrensymposium.com/program.html and are made possible through funding by the Dupuytren Foundation. Please support further research and education by giving to the Dupuytren Foundation at http://CureDup.com

Dr. Meinel presents a new concept of Dupuytren's at the Miami Dupuytren Symposium

Dr. Albrecht Meinel, former chief of surgery for over 20 years at Tauberbischofsheim Hospital, Germany, shares his insights from a lifetime interest in Dupuytren's contracture with the paradigm-shifting presentation "The palmar fibromatosis or the loss of flexibility of the palmar finger tissue. A new insight into the disease process of Dupuytren’s contracture based on clinical and anatomical findings." We need both luck and lateral thinking to develop better treatments for Dupuyten's, and Dr. Meinel's concept of extension blocking as the basic mechanical biology of Dupuytren's turns conventional thinking on its head: http://www.youtube.com/user/DupuytrenFoundation#p/u/0/kq4hr06tOtY 

Dr. Paul Werker presents at the 2010 Dupuytren Symposium

Paul Werker MD PhD, Professor and Head of the Department of Plastic Surgery, Groningen University Medical Center Groningen, NL presents: Management of soft tissue contractures: a surgical perspective. See the video at http://www.youtube.com/user/DupuytrenFoundation#p/u/0/fHoOhGlsgDU. This and other video presentations from the 2010 International Symposium on Dupuytren's Disease, are being added to http://dupuytrensymposium.com/program.html. This symposium was made possible through funding from the Dupuytren Foundation. Join the effort to find a cure by making a donation to support research, education and global collaboration through the Dupuytren Foundation: http://CureDup.com.

The search for a cure

http://www.youtube.com/user/DupuytrenFoundation#p/u/0/a5iYXAdZCYc

Video: Dr. Rayan at the 2010 Miami Dupuytren Symposium

Dr. Ghazi Rayan, reviews Dupuytren's disease: anatomy, pathology, presentation at the 2010 Miami Dupuytren's Symposium: http://www.youtube.com/user/DupuytrenFoundation#p/u/0/HE6nBpteAAo. Dr Rayan is Program Director, Hand/Orthopaedic Surgery, INTEGRIS Baptist Medical Center, Oklahoma City, OK, and is a world expert on the problem of Dupuytren's disease. Dr. Rayan has authored a number of papers on this condition in addition to co-authoring the 2003 book "Dupuytren's Disease - a concept of surgical treatment", published by Springer Verlag. Additional videos from this symposium are available free through http://dupuytrensymposium.com/program.html, sponsored by the Dupuytren Foundation. Support more work like this by donating to the Dupuytren Foundation: http://CureDup.com.

Video: Dr. Osterman at the 2010 Miami Dupuytren Symposium

The latest installment of video presentations archived from the Miami Dupuytren Symposium features Dr. Lee Osterman, Professor of Hand/Orthopedic Surgery at the Thomas Jefferson University in Philadelphia, PA. Dr. Osterman's entertaining presentation highlights the complex background of efforts to understand and treat Dupuytren's Disease. See "Cline’s contracture: Dupuytren was a thief. A history of surgery for Dupuytren’s contracture." at http://www.youtube.com/user/DupuytrenFoundation#p/u/0/iOd0iZNbM_w. If you missed or had audio difficulties with previously posted symposium videos, check http://dupuytrensymposium.com/program.html for updated versions and new releases.

Video: Dr. Wolfgang Wach at the 2010 Dupuytren Symposium

Dr. Wolfgang Wach, founder of the Dupuytren Society (http://www.dupuytren-online.info/), discusses the development, value and future of the Dupuytren Society in this video from the 2010 International Symposium on Dupuytren's Disease. The Dupuytren Society is the largest, most visited patient oriented Dupuytren's resource on the internet. http://www.youtube.com/watch?v=F_8did7Pr78

Video Presentations of the 2010 Miami Dupuytren Symposium on YouTube

The Miami Dupuytren Symposium was very exciting. Presentations were recorded on video, and are finally making their way through post processing to be available on line. Free. For you - courtesy of the Dupuytren Foundation. These will be released weekly. Each presentation is at least 15 minutes, and most will take some time to digest, so get comfortable, and get to know the people who are working around the world to find a cure for Dupuytren's and related conditions.

The first video is the introductory and welcoming remarks by Dr. Charles Eaton.
http://www.youtube.com/user/DupuytrenFoundation#p/u/0/E4qAoklf4sE

Enjoy!

Scientific breakthroughs at the Miami Dupuytren Symposium

It's been a few months since the 2010 International Symposium on Dupuytren's Disease in Miami, FL. This was a huge undertaking - the the first meeting of this scope and magnitude in 20 years, and some incredible new developments were showcased. There was so much material presented it's taking a while to sort through things, but work is underway to publish a textbook based on the proceedings (Springer-Verlag) as well as publish on line videos of the presentations. We will be going through these presentations over the next few months on this site, but in the mean time, the entire book of presentation abstracts and speaker biographies is available at http://www.dupuytrenfoundation.org/DupPDFs/2010_DupuytrenSymposium.pdf

Enjoy!

Miami International Dupuytren Symposium Breaks New Ground

Medical researchers and physicians from 15 countries converge May 22 and 23 at the Intercontinental Hotel in Miami for an intensive two day summit on Dupuytren's Disease: www.DupuytrenSymposium.com. Dupuytren's disease is a progressive condition which gradually curls the fingers permanently into the palm. It is estimated that 3 to 9 million Americans have bent fingers from Dupuytren's. Currently, there is no cure. The goals of this symposium are for experts to share new information and to organize for the first time an international coalition of doctors and scientists who will work together to develop better options for treating this crippling genetic disease. This is a major step toward finding a cure.

Dupuytren's Disease is a "silent" condition because it affects seniors, progresses slowly, and can escape notice by others until it is fairly advanced. It is common enough that many public figures have been afflicted, including Ronald Reagan, Margaret Thatcher, playwright Samuel Beckett, pianist Misha Dichter, actors Bill Nighy and David McCallum, as well as James Barrie, author of "Peter Pan", who is believed to have based Captain Hook's hand on his own. Progress in treating Dupuytren's has potential impact on the treatment of other life altering conditions such as pulmonary fibrosis, scleroderma, renal fibrosis and cirrhosis of the liver.

The 2010 International Symposium on Dupuytren's Disease is hosted by The Dupuytren Foundation, www.DupuytrenFoundation.org, a 501(c)(3) public charity established to promote research, education and global collaboration towards finding better treatment options for Dupuytren's and related conditions.

Stony Brook Dupuytren Symposium

I had the opportunity to attend the Stony Brook Dupuytren Symposium April 17. This was a real treat, featuring a faculty of well known authorities on Dupuytren's. The volcanic ash European flight difficulties prevented attendance of only one speaker. The symposium covered a range of topics and in addition provided an in depth tour of the use of collagenase injection for Dupuytren's from the initial concept, through proof of concept in laboratory tests and then clinical trials, to clinical application, indications and issues. This is a monumental achievement for Drs. Hurst and Badalamente, and a testimony to their insight and persistence. Plans were also discussed to jointly present the materials from the Stony Brook and the upcoming Miami Dupuytren Symposium (http://www.DupuytrenSymposium.com) together as one book, to be published by the American Society for Surgery of the Hand (http://www.assh.org). What a promising year for Dupuytren's!

Stretching, Myofibroblasts and Dupuytren's

How, and why, does Dupuytren's disease actually contract? What is the physical mechanism? What provokes it? There is a genetic risk, but genes don't provide the entire script, otherwise Dupuytren's contractures should be symmetric, the same problem developing at the same time in the same way in both hands, but that's not what happens: usually, contractures in one hand are different in time and space than the other hand. Why? One explanation is that Dupuytren's is both biological and mechanical, and that physical forces somewhat influence the process. One way to study the big picture is to look at the little picture: what happens inside Dupuytren cells in response to physical forces? This is an active and exciting area of research. Myofibroblasts are the contracting cells producing Dupuytren's and other fibrotic contractures. Myofibroblasts respond to stretching by first relaxing and then pulling against the line of pull. This process is the subject of ongoing studies. In "Stretch-activated force-shedding, force recovery, and cytoskeletal remodeling in contractile fibroblasts" (full text: http://www.dupuytrenfoundation.org/DupPDFs/2008_Nekouzadeh.pdf), researchers used a laboratory model to demonstrate fibroblast reactions to stretch. Stretching cells initially tears the scaffolding inside cells, which is made of the protein actin. This releases tension, but also provokes the cells to pull back in two phases. The first phase starts within seconds ("Rapid Active Response"), the second after a few minutes ("Gradual Active Response"). These responses show the cell repairing the torn proteins. Other responses follow, modifying the collagen matrix outside the cells. The result? The more you pull, the more Dupuytren's pulls back. This is the type of data we need to move past what would seem to make sense, but is probably exactly wrong (pulling and stretching your fingers back to keep them from contracting) to an effective treatment, a cure.

Personal experiences with Xiaflex and Needle Aponeurotomy

Xiaflex is now available, and is generating reports by both traditional writers and self published social media authors. There are now two minimally invasive treatments for contractures due to Dupuytren's disease - Xiaflex injection and needle aponeurotomy - with relative advantages and disadvantages of each. The following video was made by a Dupuytren's patient, documenting experience with needle aponeurotomy: http://www.youtube.com/watch?v=lGD9RjmFBzo. Another person's documentary experience with Xiaflex, also with videos, is posted here: http://bit.ly/9RhqQA. Their experiences were different, but both are satisfied with their results. Every hand is different and no one treatment works for everyone, but it's great that there are new options to choose from to buy time while researchers work for a cure. The Dupuytren Foundation is actively recruiting volunteers and fund raising options to develop better treatments - and eventually a cure. Support the effort. Make a difference. http://www.DupuytrenFoundation.org

Red wine and yellow curry to prevent Dupuytren's?

Could a yellow curry dinner and a glass of red wine be good for Dupuytren's? Possibly. Dupuytren's is a fibrotic condition, something it shares with other disorders. There is a great deal of ongoing research into the biology of fibrosis and its possible treatment. Two studies suggest that diet may have an helpful influence on excessive fibrosis, at least in special circumstances. In "Protective Effects Of Curcumin Against Amiodarone-Induced Pulmonary Fibrosis In Rats" (full text: http://www.dupuytrenfoundation.org/DupPDFs/2003_Punithavathi.pdf), researchers found a protective effect against lung fibrosis of curcumin, found in turmeric, the spice which gives the yellow color to curry and yellow rice. Another group reported in "Ochratoxin A–Induced Renal Cortex Fibrosis and Epithelial-to-Mesenchymal Transition: Molecular Mechanisms of Ochratoxin A-Injury and Potential Effects of Red Wine" (full text: http://www.dupuytrenfoundation.org/DupPDFs/2005_Gagliano.pdf) a protective effect of red wine against kidney fibrosis. These studies were performed on rats, testing against drugs known to cause fibrosis, which is a bit of a stretch to to Dupuytren's, but it's a start, if you are a rat, and possibly if you are human. Simple options are often the best. Keep looking for a cure!

A personal look at Dupuytren's

A family physician remembers his late father's Dupuytren's and muses on options for treatment: http://www.greatfallstribune.com/article/20100309/LIFESTYLE/3090307/Hands+become+claws+in+victims+of+Dupuytren+s. The observation "...in his final years he was wearied by the thought of 'another procedure' or treatment and decided to live with the condition" is a telling testimony for the need for better treatment options and the need to support efforts to find a cure for this common condition.

The earliest case of Dupuytren's? You'll never guess where.

A case of Dupuytren's contracture has been discovered dating back nearly three thousand years. The Monthemhat Project, a multinational Egyptology group, recently published an analysis of 18 mummies from the Third Intermediate Period from the Luxor Cachette, and report the diagnosis of Dupuytren's contracture involving the left hand of one of the mummies. The full report, "Estudio Antropológico, Paleopatológico Y Radiológico De Las Momias Localizadas En El Almacen Número 4 De La Casa Americana (El Asasif, Luxor, Egypt): Proyecto Monthemhat 2009" is available here: http://www.dupuytrenfoundation.org/DupPDFs/2009_garciaguixe.pdf. The Third Intermediate Period refers to the time in Ancient Egypt from the death of Pharaoh Ramesses XI in 1070 BC to the foundation of the Twenty-Sixth Dynasty by Psamtik I in 664 BC. If this is true, this identifies a case of Dupuytren's nearly two thousand years before the previously earliest reports of Dupuytren's in Orkney and Iceland in the 12th and 13th centuries. The question is: were the Egyptians the secret ancestors of the Vikings?

Dupuytren's or palmar fasciitis?

Dupuytren's isn't the only problem which can affect the fascia of the palm. Inflammation of the palmar fascia (palmar fasciitis) may be due to less common problems, and differs from typical Dupuytren's in that it is usually painful. The difference between Dupuytren's and palmar fasciitis is similar to the difference between Ledderhose disease and plantar fasciitis - they are completely different problems which happen to affect the same stucture. Palmar fasciitis may be part of a syndrome associated with arthritis, as reported in "Idiopathic Palmar Fasciitis with Polyarthritis Syndrome" (full text: http://www.dupuytrenfoundation.org/DupPDFs/2006_Sung.pdf), a problem following trauma as discussed in this hand surgery book exerpt (text: http://bit.ly/9Srduf) or part of a paraneoplastic syndrome associated with malignancy as reported in "Palmar fasciitis and polyarthritis as a paraneoplastic syndrome associated with tubal carcinoma: a case report" (full text: http://www.dupuytrenfoundation.org/DupPDFs/2004_Denschlag.pdf). Fortunately or not, Dupuytren's is much more common than any of these conditions, but it is important to keep these in the list of possible diagnoses when evaluating a case of Dupuytren's which doesn't fit the typical picture.

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)

ß Catenin, Transforming Factor ß and Dupuytren's

The physical changes associated with Dupuytren's are similar to the process which heals open wounds through contraction and collagen production. Thanks to sophisticated laboratory research, the molecular controls for this process are beginning to be understood. See http://multimedia.mcb.harvard.edu/anim_innerlife.html for an amazing animation of how molecular cellular controls act like tiny physical machines. In Dupuytren's, two controls are ß Catenin and Transforming Factor ß. ß-catenin is a protein which is part of the physical scaffolding in a cell. Among many functions, ß-catenin forms part of a cellular trailer hitch which locks one cell to the next, called the adherens junctions (AJs). Transforming Factor ß is a protein which is produced by some cells to activate receptors on other cells, part of the autocrine system of cell signaling. It has different effects in different situations. Both ß Catenin and Transforming Factor ß are major players in Dupuytren's type tissue contracture. How do they interact with each other? Somewhat independently, according to this study (full text http://www.dupuytrenfoundation.org/DupPDFs/2009_Poon.pdf). ß Catenin primarily activated cell migration while Transforming Factor ß mainly stimulated cell growth and contraction, which would seem to be the more important process in Dupuytren's. Interesting, but more details are needed to crack the code to find a cure.

A Sampling of Patient Information Brochures on Dupuytren's

What do health care providers think you should know or want to know about Dupuytren's? Here is a sampling of patient information materials from the government http://www.dupuytrenfoundation.org/DupPDFs/2010_NHS-ptinfo.pdf, http://www.dupuytrenfoundation.org/DupPDFs/2010_OBS-ptinfo.pdf, organizations of hand surgeons http://www.dupuytrenfoundation.org/DupPDFs/2010_AAHS-ptinfo.pdf, http://www.dupuytrenfoundation.org/DupPDFs/2010_ASSH-ptinfo.pdf, http://www.dupuytrenfoundation.org/DupPDFs/2010_BSSH-ptinfo.pdf, individual physicians and hospitals http://www.dupuytrenfoundation.org/DupPDFs/2010_eHand-ptinfo.pdf, http://www.dupuytrenfoundation.org/DupPDFs/2010_KWO-ptinfo.pdf, http://www.dupuytrenfoundation.org/DupPDFs/2002_Hurst-ptinfo.pdf, http://www.dupuytrenfoundation.org/DupPDFs/2010_Lancashire-ptinfo.pdf and hand therapists http://www.dupuytrenfoundation.org/DupPDFs/2010_Kramer-ptinfo.pdf. Of course, a wide range of information is also available on the Dupuytren Foundation web site: http://www.dupuytrenfoundation.org/What-is-Dupuytrens

Needle Aponeurotomy for Dupuytren's

Needle aponeurotomy for Dupuytren's contracture is a type of fasciotomy performed under local anesthesia. Compared to fasciectomy, it is less of an ordeal for the patient in terms of both procedure and recovery and has a lower complication rate. This report (full text: http://www.dupuytrenfoundation.org/DupPDFs/2008_Cheng_1610.pdf) reviews one group's experience with needle aponeurotomy.

Dupuytren's and Transforming Factor Beta Genetics

What is the initial abnormality which ultimately results in Dupuytren's? Because biologic systems are guided by tiny triggers which start a cascading series of events, tiny differences can have large effects, and the hunt is sometimes for tiny differences early in the game. Transforming Factor Beta One (TGF-ß1) is one of the starting players in the series of events leading to Dupuytren's, and it makes sense to look at the genes which control the production of TGF-ß1 as a possible culprit. Could Dupuytren's be due an alteration in these genes, resulting in some tiny but critical problem with TGF-ß1, the butterfly effect for Dupuytren's? The first study to look at this compared gene patterns relating to TGF-ß1 in people with and without Dupuytren's (full article: http://www.dupuytrenfoundation.org/DupPDFs/2002_Bayat_1049.pdf). It came up negative, but larger, more detailed sudies may show otherwise. More clues to find a cure.

Dermofasciectomy reconsidered

There are three mechanical approaches for Dupuytren's. In order of both increasing problems and long term effectiveness, these are: fasciotomy (cut fascia); fasciectomy (remove fascia); dermofasciectomy (remove both skin and fascia). The popularity of dermofasciectomy and skin grafting has been limited by concerns regarding complications of wound healing and loss of flexion. Some of these concerns stem from the historical use of dermofasciectomy as a revision procedure after failed fasciectomy, a group biased toward poor results. Dermofasciectomy as the primary or first operation is a different story. This study reviews technical tips for dermofasciectomy and shows that for patients with diffuse skin involvement, primary dermofasciectomy and skin grafting has a better chance of long term control than fasciectomy. http://www.dupuytrenfoundation.org/DupPDFs/2000_Armstrong_1046.pdf

Matrix Metalloproteinases and Dupuytren's

What are matrix metalloproteinases and how are they linked to Dupuytren's? Matrix Metalloproteinases (MMPs) are naturally occuring enzymes whose name describes them: they are found outside cells in the extracellular matrix, their molecular makeup includes a metal (Zinc) and they break down proteins. Human collagenase, which breaks down collagen, is in this group, and Dupuytren's may be due to an imbalance between the body's MMPs and tissue factors which block MMPs. Some cancers spread faster because they produce these enzymes, like flesh eating bacteria, which speeds up how fast they spread. Medicines which block these enzymes help fight these types of tumors. Unfortunately, a side effect of one of these medicines is activating both Dupuytren's and its sibling, frozen shoulder, as detailed in this report: http://www.dupuytrenfoundation.org/DupPDFs/1998_Hutchinson_1085.pdf. This brings up many questions: Other substances also block MMPs, like the antibiotic doxycycline - do they provoke Dupuytren's? If Dupuytren's is a natural resistance to MMPs, does having Dupuytren's give a resistance to some types of cancer? So many dots to connect on the way to a cure.

Cortisone shots for Dupuytren's nodules

Cortisone injections have been used for many years as an early treatment for Dupuytren's in the nodular stage of involvement. This approach is based on clinical experience, but what is the actual biology? It may have to do with the finding that tissue matrix as well as the blood vessel cells in Dupuytren's nodules have abnormal amounts of a helper protein, VLA4. VLA4 acts like a doorknob on a door on the blood vessel wall which lets inflammatory cells out of the bloodstream and into the nodule, where they promote inflammation and fibrosis. This study shows that cortisone injected into Dupuytren nodules reduces the activity of VLA4 in Dupuytren's nodules  back toward normal. This is only part of the picture, but provides solid clues to look into further for better treatment options: http://www.dupuytrenfoundation.org/DupPDFs/1999_Meek_1079.pdf, http://www.dupuytrenfoundation.org/DupPDFs/1999_Meek_1581.pdf

Botox and Dupuytren's

The holy grail of treating Dupuytren's contracture is "disease modification": how to stop progression or recurrence in a safe, nontoxic way? Three articles hint at the tantalizing possibility of the use of Botox (botulinum toxin) for Dupuytren's. Botox includes two classes of enzymes which affect two different biologic systems. The first enzyme, which made Botox popular, is the neurotoxin which blocks nerve signals and paralyzes muscles. The second, lesser known component is C3 transferase exonzyme, which is fascinating and completely different. C3 transferase exonzyme affects a variety of cell-cell and cell-matrix interactions involved in fibrosis. Keloid scars show increased activity in the specific pathways affected by C3 transferase exonzyme http://www.dupuytrenfoundation.org/DupPDFs/2008_Witt.pdf and botox is being reported as a treatment for keloid scars. Experimentally, botox has been shown to reduce contracture, adhesions and fibrosis after surgical wounds http://www.dupuytrenfoundation.org/DupPDFs/2009_Lee.pdf, http://www.dupuytrenfoundation.org/DupPDFs/2007_Namazi.pdf. Could Botox be the magic bullet for Dupuytren's?

Feedback Loops in Dupuytren's

The best hope for finding a medical cure for Dupuytren's and other fibrotic conditions is through a better understanding of abnormal cell signalling feedback loops regulating fibrosis. Cellular collagen metabolism regulation is not fully understood. Here are a few puzzle pieces. The protein transforming growth factor beta (TGF-ß), among other things, signals myofibroblasts to produce collagen. Plasminogen Activator is a protein which links with a cell receptor and another protein, Integrin αvß2, to activate Plasmin, an enzyme which counterbalances the effects of TGF-ß. Plasminogen Activator Inhibitor-1 (PAI-1) removes these plasmin receptors and integrins from the cell surfaces, and so too much PAI-1 promotes fibrosis. However, nothing is simple; everything is connected: Too little PAI-1 also promotes fibrosis. Why? The margin of this post is too small to include a full proof, so here is the link to the original resaerch report: http://www.dupuytrenfoundation.org/DupPDFs/2009_Pedroja.pdf

The New Dupuytren Foundation Web site is live!

The Dupuytren Foundation has a new web site! It's taken a lot of work, but the new web site for the Dupuytren Foundation is live. Looks nicer, works better, and more to come. http://DupuytrenFoundation.org

The Dupuytren Symposium is coming!

As tomorrow's deadline for abstract submission nears, internet connections are heating up at command central for the 2010 International Symposium on Dupuytren's Disease. The symposium syllabus looks very exciting, with some amazing new reports. Session topics have solidified as: The Myofibroblast; Genetics and Demographics; Disease Concepts; Collagen and Collagenase; Surgical Treatments; Energy Based Treatments; Manual Therapies; The Future. The Saturday evening dinner presentation will be on the life of Dupuytren. Overall, everything is shaping up well, so get ready. Stragglers, submit your abstracts! Otherwise, register to attend - space will be limited! http://www.DupuytrenSymposium.com

Dupuytren's Review

Despite being a visible, obvious problem, Dupuytren's is difficult to understand, like the Jimmy Buffet line "so simple - like the jitterbug - it plumb evaded me". It is helpful to review the basics on a regular basis to keep a clear perspective. Here is a great review for hand surgeons and non hand surgeons alike: http://www.dupuytrenfoundation.org/DupPDFs/2006_Townley_1216.pdf

Needle Release of Dupuytren's: 2010 Manual of Technique

Percutaneous fasciotomy for Dupuytren's contracture is an old procedure, but was reinvented by Dr. Lermusiaux in Paris in the 1980s, who used a small needle rather than a scalpel. This modification allows the procedure to be performed using almost no anesthesia, which gives an unprecedented safety margin: the patient can easily confirm whether nerves or tendons are in harm's way. The technique made its way into the USA in 2003. The most recent 2010 manual of technique for this procedure presents the approach and recommendations refined during over 5000 procedures by Dr. Eaton in Florida: http://www.dupuytrenfoundation.org/DupPDFs/2010_Eaton.pdf

Fifty years of Dupuytren's Patients Reviewed

One of the more puzzling things about Dupuytren's is the variation in demographic data. Taking away the variation in results from different surgeons doing different operations, one would expect a standard pattern of who is at risk, what conditions are associated. Not so. A review of nearly 3000 Dupuytren patients seen over 50 years at one institution found these trends in their group, some of which are at odds with earlier reports: nearly half of involvement was bilateral, right hand slightly more common than left when only one hand was affected; diabetes, alcoholism and smoking were only weak risk factors; more than one digit was involved in over half of the affected hands; men outnumbered women 7.6:1 and on the average developed Dupuytren's 10 years younger than women. There are other details which make it worth reading the full text, including surgical results and the effectiveness of external fixation to avoid amputation: http://www.dupuytrenfoundation.org/DupPDFs/2007_Loos_1033.pdf