Lessons from Peyronie's for Dupuytren's

Peyronie's disease is more common than Dupuytren's - 3 to 9 percent of the population - and shares a similar biology and genetic predisposition. Progress in the treatment of Peyronie's will benefit that of Dupuytren's and vice versa. Taken in this context, these two articles by Hellstrom from 2000 and 2009 are very thought provoking. Animal model? Oral, topical or intralesional medication? Radiation? Shockwave treatment? Could these be applied to Dupuytren's?
http://www.dupuytrenfoundation.org/DupPDFs/2000_Hellstrom.pdf
http://www.dupuytrenfoundation.org/DupPDFs/2009_Hellstrom_397.pdf

Looking at Dupuytren's with MRI

Where is Dupuytren's? It's been known for some time that Dupuytren's involvement can be identified by MRI, as described in these articles:
http://www.dupuytrenfoundation.org/DupPDFs/1993_Yacoe_813.pdf
http://www.dupuytrenfoundation.org/DupPDFs/1994_Miller.pdf
and it's likely that the activity of the process could be mapped, both for predictive value and for targeted treatment to prevent progression. Now, these papers are 15 years old - it's time to revisit this with more up-to-date imaging technology to look again at the usefulness of MRI and Dupuytren's in a longitudinal study - might make a nice PhD thesis...

The Fish Technique for Dupuytren's: Fasciectomy and Skin Graft

Skin grafts are used in a variety of approaches for Dupuytren's: to add skin where it has been shortened (fasciotomy and skin graft, fasciectomy and skin graft); to replace skin where it has been removed to prevent recurrence (dermofasciectomy and skin graft). This study reviews the results of fasciectomy and skin graft. The recurrence rate was better than simple fasciectomy: 7% recurrence rate at four years. The study also reminds us that for Dupuytren's, even smart surgery by skilled surgeons has significant downsides: three of ten patients lost some feeling in their fingers and four out of ten had cold sensitivity as a direct result of surgery. We need even better treatment options.
http://www.dupuytrenfoundation.org/DupPDFs/2006_Roy.pdf

Accidental fasciotomy for Dupuytren's

Fingers bent by Dupuytren's can complicate a fall on an outstretched hand: because the fingers can't stretch back, the force of impact is redistributed, making it more likely to break hand bones. When the fall is hard enough to break something, occasionally what gives is not bone, but the Dupuytren cord. This usually is accompanied by a tear in the skin. Although the final outcome is often surprisingly good, it's not recommended as a primary treatment. This report describes a patient with an unusual traumatic partial rupture of a Dupuytren's cord: http://www.dupuytrenfoundation.org/DupPDFs/1995_Darcangelo.pdf

No advantage to open Proximal Interphalangeal Joint release for Dupuytren's

Proximal interphalangeal joint contractures from Dupuytren's disease take on a life of their own, persisting after the Dupuytren's has been removed. One of the arguments for open fasciectomy is that PIP contractures can be treated by openly releasing the tight joint capsule and ligaments. Unfortunately, gains made in the operating room are lost during the recovery period, and after the dust settles, open joint releases for PIP contractures associated with Dupuytren's are ineffective in the long run, as reviewed in these three reports from three different institutions:
http://www.ncbi.nlm.nih.gov/pubmed/8596787
http://www.ncbi.nlm.nih.gov/pubmed/15142694
http://www.ncbi.nlm.nih.gov/pubmed/14734062

Dupuytren's and Burns

Dupuytren's overlaps in some ways with the local excessive scarring which occur after a burn injury. This report documents the development of progressive Dupuytren's disease developing in a young man after a hand burn, and reviews the conventional teachings regarding Dupuytren's: http://www.dupuytrenfoundation.org/DupPDFs/2008_Balakrishnan_1422.pdf

Gene Expression in Dupuytren's

If Dupuytren's is inherited, what are the genes involved? Difficult question. Every cell in a person's body has the same genes, but every cell is not the same. The differences between cells are not from different genes, but from differences in gene expression: every cell in the body is like a tiny computer; chromosomes are the hard drive and genes are the programs on that hard drive, and to this extent, every cell in a person's body is identical. However, just as two identical computers can run different programs, different genes being expressed are like different programs running. Cells involved with Dupuytren's are running the wrong programs. Just looking at the genes doesn't tell what is actually going wrong - it's necessary to look at the programs which are running, which genes which are being "expressed". This study documents progress in the effort to identify gene expression associated with Dupuytren's, the master key to the puzzle: http://www.dupuytrenfoundation.org/DupPDFs/2008_Satish_1556.pdf

ß-catenin, Wnt and Dupuytren's

Ultimately, Dupuytren's has to do with cell signalling: normal cells are somehow instructed ("signalled") to become abnormal, and adjacent cells interact with each other in a progression of abnormal changes. One of the many ways that cell signal each other is the Wnt signaling pathway, which involves a series of proteins which trigger cascades of events inside individual cells. One of these proteins is ß-catenin. ß-catenin is associated with some processes in which cells physically attach to each other. It can also affect the cell nucleus and activate specific genes. ß-catenin builds up abnormally in Dupuytren cells and may be part of the cause. What causes this? The Wnt pathway is a likely candidate: some ß-catenin interactions are involved in the Wnt pathway. However, this study appears to show that abnormal ß-catenin levels in Dupuytren cells are not due to effects of the Wnt pathway, which brings a better understanding of the biology: one suspect crossed off of the list: http://www.dupuytrenfoundation.org/DupPDFs/2006_O'Gorman_1565.pdf

Stretching may provoke Dupuytren's

The relationships between mechanical forces and the biochemistry of Dupuytren's are only recently being sorted out. Clinically, Dupuytren's activity responds to changes in mechanical stresses: active nodules soften in response to reducing tension by adjacent fasciotomy; disease activity after fasciectomy may be provoked by overly aggressive stretching and splinting. Biochemically, this may relate to the finding that, in contrast to cells from normal fascia, cells from Dupuytren's tissue produce ß-catenin and fibronectin in response to stretching forces: http://www.dupuytrenfoundation.org/DupPDFs/2003_Howard_1029.pdf

The Open Palm Technique for Dupuytren's

The Open Palm Technique for Dupuytren's contracture has advantages - lack of hematoma, lower incidence of sympathetic dystrophy. The classic McCash version of this procedure combines closure of zigzag finger incisions, leaving transverse palm wounds open. The Burkhalter version, developed by Dr. Mann, employs only transverse incisions in the palm and fingers, all of which are left open. Proponents of the Burkhalter technique believe that it leads to fewer recurrences, but there are no studies yet to back this up. Available evidence suggests that individual patient biology is the main influence on recurrence and that the incidence of some complications varies with procedure. This study of the McCash open palm technique confirms that the rates of complications (21%) and recurrence (33% at 2 1/2 years) remain issues even the hands of experienced surgeons: http://www.dupuytrenfoundation.org/DupPDFs/1994_Cools.pdf

Chondroitin Sulfate, Dermatan Sulfate and Dupuytren's

Dermatan sulfate is similar to the nutritional supplement chondroitin sulfate, and used to be called chondroitin sulfate. Dermatan sulfate is unusually abundant in fascia affected by Dupuytren's. Is it the cause or is it the effect of the abnormal biology of Dupuytren's? Maybe both, as discussed in this review: http://www.dupuytrenfoundation.org/DupPDFs/2007_Kozma.pdf

Open fasciotomy for Dupuytren's

 Patients with Dupuytren's need two things, mechanical and biological. The former, a simple and safe way to straighten bent fingers, and the latter, a way to prevent disease progression and recurrence. This article reviews pros and cons of a simple mechanical treatment, open fasciotomy, for severe contractures in a group of elderly patients: http://www.dupuytrenfoundation.org/DupPDFs/2007_Jablecki.pdf

Genetic determined biochemistry and Dupuyren's

The genetic basis of Dupuytren's is explained by the genetic basis of individual biochemistry and enzymatic variation. Sort of. This fascinating review shows how complicated this can be: http://www.dupuytrenfoundation.org/DupPDFs/2008_Zyluk.pdf

Verapamil, tamoxifen, carnitine - options?

One resource for potential medical treatment of Dupuytren's is the literature on medicines which work for related conditions such as Peyronie's. This review examines the rationale and results of propionyl-L-carnitine, acetyl-L-carnitine, verapamil and tamoxifen in treating Peyronie's disease. Is there a role for these in Dupuytren's? http://www.dupuytrenfoundation.org/DupPDFs/2002_Cavallini.pdf

Dupuytren's and Frozen shoulder

About one in six patients with frozen shoulder will also have Dupuytren's disease and vice versa. Frozen shoulder has been called "Dupuytren's of the shoulder": the abnormal tissues are quite similar. However, they are different in other respects - for example, Dupuytren's commonly recurs after surgical treatment, but frozen shoulder does not. This study demonstrates how biomechanical tissue responses to stimulation differs in these two conditions, which may help explain this: http://www.dupuytrenfoundation.org/DupPDFs/2006_Bains_43.pdf

Vascular cause of Dupuytren's?

Diabetes, hypertension, stiff finger joints and Dupuytren's: This study uses retinopathy as an index of vascular disease and suggests that small vessel disease, rather than the effect of blood sugar on collagen, is the link between diabetes and Dupuytren's: http://www.dupuytrenfoundation.org/DupPDFs/1986_Larkin_1218.pdf

Peyronie's Disease and Dupuytren's

Dupuytren's is one manifestation of a systemic fibrotic disorder that can also show up as Ledderhose, frozen shoulder or Peyronie's disease. Fortunately, the majority of people affected show only one of these conditions, but many have to deal with several or all of these. This summary reviews the condition referred to as Peyronie's disease: http://www.dupuytrenfoundation.org/DupPDFs/2009_NIDDK.pdf

A landmark advance in understanding Dupuytren's

Two methods of investigating Dupuytren's have been used: Demographic - family studies, associations with medications, activities, other diseases; and Biological - tissue analysis. The big biologic breakthrough came in 1972 when Gabbiani and others published two articles back to back findings on the biology of myofibroblasts:
http://www.dupuytrenfoundation.org/DupPDFs/1972_Gabbiani_719.pdf
and the role of myofibroblasts in Dupuytren's Disease:
http://www.dupuytrenfoundation.org/DupPDFs/1972_Gabbiani_1115.pdf
We need more breakthroughs like this to develop biologic treatments for Dupuytren's.

Smooth Muscle Actin in Dupuytren's Contracture

The palmar fascia in Duputren's contracture does not contract like a muscle: it's more like the effect of an army of tiny rachets. Adjacent parallel strands of collagen are grabbed by myofibroblasts, which then shorten ("crimp") lengthwise, pulling the strands to overlap more and more, and then gluing these strands together with crosslinks. Crimp, lock, crimp, lock, shortening the fabric in one direction. Crimping is accomplished by the action of one type of smooth muscle actin (SMA) inside myofibroblast cells. This study looks at the presence of SMA in Dupuytren's tissues, and suggests that one of the five types of platelet derived growth factor, PDGF-BB, might be used to selectively block SMA and prevent contracture:
http://www.dupuytrenfoundation.org/DupPDFs/2003_Hindman_1072.pdf

CMMS therapy for stiffness after fasciectomy for Dupuytren's

Stiffness is a common problem after fasciectomy, particularly loss of flexion, and can be resistant to stretching exercises or splints. This therapy program, incorporating a combination of casting and active exercises, helped patients regain motion when they had failed conventional hand therapy: http://www.dupuytrenfoundation.org/DupPDFs/2007_Rose.pdf

NICE evaluation of needle aponeurotomy for Dupuytren's

The source of medical information is critical; objectivity is essential. That's one of the advantages of the UK's NHS independent review process. Read their assessment of needle aponeurotomy:
http://www.dupuytrenfoundation.org/DupPDFs/2004_NICE.pdf

Drugs that provoke Dupuytren's Disease

Looking for ways to stop Dupuytren's, it should be useful to look in reverse at factors which may start it, such as protease inhibitor drugs, as reported here: http://www.dupuytrenfoundation.org/DupPDFs/2002_Florence_1607.pdf

Dupuytren's, Mast cells, Substance P

Dupuytren's is not always painless. Sometimes, active areas itch and burn. This goes along with the finding of elevated levels of mast cells and nerve fibers containing substance P - something also found in interstitial cystitis. Find out more at http://www.dupuytrenfoundation.org/DupPDFs/2006_Schubert_1071.pdf

Aggressive Dupuytren's Disease

This report of Dupuytren's extending from the palm into the forearm reviews the anatomy of involvement and points out the aggressive nature of Dupuytren's in young people. We need more effective biologic treatments: http://www.dupuytrenfoundation.org/DupPDFs/1997_Sinha_1048.pdf

Dupuytren' s Contracture - Microscopic Analysis

This is a classic article on the biology of Dupuytren's. Structural changes in the palmar fascia are associated with type III collagen, which isn't normally found in this tissue. Myofibroblasts are likely the source of this and are associated with disease recurrence.Most important quote: "Clinical recurrence was not related to the age of
the patient at onset, duration, or severity of disease. Recurrence was related to the electron microscopic
findings of myofibroblasts in the nodules and fibroblasts containing prominent microtubules in the fascia
of these patients." Wouldn't it be great to have a way to have this assessment before treatment?
http://www.dupuytrenfoundation.org/DupPDFs/1980_Gelberman_425.pdf