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