Thursday, December 31, 2009

Management strategies for Dupuytren's

The management options for people with Dupuytren's can appear as confusing as the biology. This review provides a nice overview of Dupuytren's disease and a practical decision tree approach to manage hands affected by Dupuytren's. It's worth a read: http://www.dupuytrenfoundation.org/DupPDFs/2006_Bayat_1586.pdf

Tuesday, December 29, 2009

Homeopathy for Dupuytren's

HH Reckeweg (1905-1985) in Germany developed the Disease Evolution Table of homeopathic medicine. In this system, Dupuytren's contracture is classified as a mesenchymal-connective tissue cellular-degeneration phase disease. This should be the starting point for homeopathic physicians to begin developing a homeopathic cure for Dupuytren's. See where Dupuytren's fits on the Disease Evolution Table:  http://www.dupuytrenfoundation.org/DupPDFs/1985_Reckeweg.pdf

Monday, December 28, 2009

Machines to Stretch Dupuytren's Cords

There is not yet a perfect solution for PIP contractures from Dupuytren's Disease, or for PIP contractures in general. One approach has been to use temporary skeletal fixation devices to slowly lengthen Dupuytren's cords and scar tissue. The collagen bundles in Dupuytren's cords don't actually stretch: they remodel, disconnecting crosslinks between adjacent strands, sliding adjacent strands relative to each other and then forming new crosslinks. On a microscopic level, this is architecturally the opposite of the process by which Dupuytren's cords shorten. This brief review summarizes the experience of several groups in developing such devices along the road to designing the Digit Widget. http://www.dupuytrenfoundation.org/DupPDFs/2002_Goss.pdf

Sunday, December 27, 2009

Tissue markers for Dupuytren's

Is it possible to predict the course of Dupuytren's in an individual? Who will need surgery? Who will have rapid progression or an early recurrence after surgery and who won't? Family and personal history provide general trends, but that's all. Several studies have correlated the cellularity of nodule tissue and the presence of myofibroblasts with the risk for recurrence or "aggressive" Dupuytren's. This study found in addition, alpha smooth muscle antigen and the MK167 gene related Ki-67 protein correlated with aggressive disease, the markers for tenascin and factor XIIIa less so. Unfortunately, these differences were a matter of degree, not absolute. What are the actual pieces of this puzzle?  http://www.dupuytrenfoundation.org/DupPDFs/2005_Forsman_1055.pdf

Saturday, December 26, 2009

Dupuytren's, epilepsy, barbiturates and genes: a chemical love ...triangle.

Dupuytren's has been associated with epilepsy. The type or cause of epilepsy doesn't seem to matter. What does matter is the specific medication phenobarbitone. Dupuytren's was not common in epileptics prior to the common use of this medicine, but is very common in people on long term treatment with it: Dupuytren's will be found in half of men having 20 years of pentobarbitone treatment. This is a huge number, and presents a problem: how can this be reconciled with the concept of an inherited disorder if the incidence of pentobarbitone related Dupuytren's is larger than the expected Dupuytren gene pool? Does pentobarbital activate Dupuytren genetic or cytokine pathways in the absence of a genetic risk for Dupuytren's? Once again, more questions than answers. http://www.dupuytrenfoundation.org/DupPDFs/1976_Critchley_1447.pdf

Friday, December 25, 2009

Treatment effectiveness for Dupuytren's needs documentation

Progress into new territory requires an open mind: beware conformity; examine failure; engage outsiders, and be aware of undocumented claims. This interesting report of an injection treatment for Dupuytren's would be worth considering if published in an independent peer reviewed format rather than on the manufacturer's web site: http://www.dupuytrenfoundation.org/DupPDFs/2001_Beller.pdf

Thursday, December 24, 2009

Rock Climbing and Dupuytren's - an interesting analysis

Dupuytren's is an inherited systemic disorder of either the threshold or the feedback inhibition of the biology of scar formation, contracture and maturation. It is not spontaneous, but triggered in specific areas having the common characteristic of being subjected to repeated high shearing or stretching forces: palmar fascia, plantar fascia, shoulder capsule, tunica albuginea of the penis. These areas are able to produce the perfect storm of tissue conditions which activate the process. Dupuytren's is not just a reaction to mechanical forces: they are a small, but definite part of the picture, and may just speed up the timescale of activating the process.
http://www.dupuytrenfoundation.org/DupPDFs/2005_Logan_1606.pdf

Wednesday, December 23, 2009

How the FDA sees Collagenase for Dupuytren's

Why is it taking so long for collagenase injection treatment to be available to treat Dupuytren's? Trials have been ongoing for over 10 years. The answer: collagenase is an extremely potent substance, and the FDA has required very detailed proof not only that it works, but that it is safe, and that it has something to offer better than existing treatment. This FDA presentation provides the actual data from trials on collagenase, the good, the bad and the strange. The bar is pretty low to choose collagenase over fasciectomy, but the question of choosing collagenase over needle aponeurotomy remains unanswered. http://www.dupuytrenfoundation.org/DupPDFs/2009_FDA.pdf

Tuesday, December 22, 2009

Abstracts can be misleading

Unlike proximal interphalangeal joint contractures from Dupuytren's, metacarpophalangeal joint contractures usually respond so well to fasciectomy or fasciotomy that joint capsule or ligament release is generally not a consideration. Because of this, I was intrigued by the title of this report: a series of patients treated with dermofasciectomy and MP joint release - it's an unusual combination. What I found instead was that the original report must have been lost in translation: the text describes fasciectomy but calls it dermofasciectomy; the pictures show a mix of proximal interphalangeal joint and metacarpopalangeal joint contractures; the statistical analysis reports 1/25 as 2.5% instead of 4% in reporting complications. Reinterpreted along these lines, the results are similar to previous reports of fasciectomy and proximal interphalangeal joint release, which is apparently what this report actually describes. http://www.dupuytrenfoundation.org/DupPDFs/2003_Saleh.pdf

Monday, December 21, 2009

Myofibroblast Biology

Myofibroblast biology is at the heart not only of Dupuytren's, but of other diseases not related to Dupuytren's. Myofibroblasts are major players in pulmonary fibrosis, cirrhosis, renal fibrosis and arteriosclerosis. Studies of myofibroblast biology in these conditions may shed light on potential new treatment strategies for Dupuytren's. Gains in the management of any one myofibroblast related condition may benefit others. This review paper covers myofibroblast biology outside the realm of Dupuytren's and a number of possible targets for biological intervention - for example: could topical nitroglycerin work for Dupuytren's? http://www.dupuytrenfoundation.org/DupPDFs/2007_Hinz_1450.pdf

Sunday, December 20, 2009

Pregnancy, Dupuytren's and Relaxin

Relaxin is a natural hormone which does many things and normally increases during pregnancy. It has been shown to have a range of antifibrotic actions: it inhibits collagen synthesis, increases collagenase activity, inhibits the profibrotic factors TGFß and Interleukin1-ß, and prevents fibroblast differentiation into myofibroblasts. How does it work? Is Dupuytren's related to low relaxin levels? Could it have a possible role in treating Dupuytren's? Could pregnancy help prevent Dupuytren's and is that why Dupuytren's is more common in men than women? There are more questions than answers, which is the necessary first step toward progress. http://www.dupuytrenfoundation.org/DupPDFs/2005_Samuel.pdf

Saturday, December 19, 2009

Friday, December 18, 2009

To understand Dupuytren's, first understand women.

Is Dupuytren's a tumor - an independent growth, or is it a reaction of normal tissues to a stimulus? Is a woman one person or several people sharing the same body? This paper answers both questions. Every female human has two X chromosomes, one from each parent, but in any individual cell, only one X chromosome is active, the other permanently inactivated. One X chromosome rules half of a woman's cells, the other rules the other half, and these cells are evenly mixed throughout her body. Now, true neoplastic tumors are clones: one cell reproduces over and over, and so in females all cells of a tumor will have the same active X chromosome. In contrast, reactive tumors are many adjacent cells responding to a common stimulus, and will have a normal mix of active X chromosomes. This fact was used to show that Dupuytren's nodules are not true tumors, not bad cells, but a reaction of normal cells to some stimulus. What is it? http://www.dupuytrenfoundation.org/DupPDFs/2006_Wang_1040.pdf

Thursday, December 17, 2009

Fasciotomy versus fasciectomy for Dupuytren's

Fasciectomy and fasciotomy were compared in this study with some interesting observations. Initially after procedure, fasciotomy was better than fasciectomy in straightening fingers, but this advantage was lost over time as fasciotomy had earlier recurrences than fasciectomy. Fasciectomy had better results at correcting PIP joint contractures, both early and late. Recovery time was longer and permanent complications, particularly stiffness, were more common for fasciectomy than fasciotomy: one out of twenty fasciectomy patients lost finger flexion compared to none of the fasciotomy patients. Fasciotomy has evolved considerably since this publication, and it will be interesting to compare fasciectomy with needle fasciotomy and enzymatic fasciotomy when results are available. http://www.dupuytrenfoundation.org/DupPDFs/1976_Rodrigo.pdf

Wednesday, December 16, 2009

Partial Fasciectomy for Dupuytren's

Dupuytren's patients need two things: first, a way to prevent disease progression and recurrence; second, the simplest, safest way to straighten fingers bent by Dupuytren's. While working and waiting on the first, there are choices for the second. One of these is limited or partial fasciectomy, which has the advantage of quick recovery and low complication rate compared to more extensive fasciectomy. There are several technical variations of this approach. Here's one: http://www.dupuytrenfoundation.org/DupPDFs/1963_Freehafer.pdf

Tuesday, December 15, 2009

TGF-ß2 and Dupuytren's

What if Dupuytren's is due to slightly abnormal levels of a normal hormone, protein or other molecule in the system? If so, one of the most likely suspects would be Transforming Growth Factor Beta Two: TGF-ß2. This protein is part of the autocrine system (a chemical instant messaging system which lets individual cells communicate with each other) and it has been shown to activate collagen contraction by fibroblasts. This study looked at the behavior of fibroblasts in a 3D living model of normal fibrous tissue, the Fibroblast Populated Collagen Lattice (FPCL), and found that although Dupuytren fibroblasts react more to the effects of TGF-ß2 than normal fibroblasts, they are abnormally active compared to normal fibroblasts even when all TGF-ß2 is removed from the system. Great! One suspect to cross off the list: http://www.dupuytrenfoundation.org/DupPDFs/2004_Tse_1031.pdf

Monday, December 14, 2009

Deformity, aggressiveness and severity of Dupuytren's

When is the most effective time to treat Dupuytren's and what is the best treatment? These are not easy questions. Dupuytren's responds differently and recurs differently in different people: starting with the same deformity (how bent the fingers are), people who do worse are described as having "aggressive" Dupuytren's. Severity is a combination of the measure of deformity and an estimate of aggressiveness. Genes determine whether or not someone will develop Dupuytren's and to a degree how aggressive it will be. External factors, such as alcoholism, amplify aggressiveness. Optimum treatment would be individualized based on severity, but a standard evaluation of all available factors is needed. This report analyzes a new system for estimating severity of Dupuytren's: http://www.dupuytrenfoundation.org/DupPDFs/2008_Hindocha_1014.pdf

Sunday, December 13, 2009

Sex and Dupuytren's in Boston

Dupuytren's is fairly common in Boston, but seems different than the European flavor in terms of sex. The numbers on almost 2000 Boston Dupuytren's patients were sorted out, and here's how things roll in Boston: men develop Dupuytren's almost twice as often as women, but it may seem like more because men tend to get the disease at a younger age, are almost twice as likely to have surgery if they do get Dupuytren's, and are more likely to have recurrences after surgery. Why? http://www.dupuytrenfoundation.org/DupPDFs/2007_Anthony.pdf

Saturday, December 12, 2009

Monkey model for Dupuytren's

An experimental monkey model of Dupuytren's Disease was performed to confirm or refute the microtrauma hypothesis of Dupuytren's. The outcome: the reaction to rupture of the palmar fascia produced lesions identical to those of early Dupuytren's, although did not lead to contractures during the period of study. The conclusion was that trauma is not the entire picture: "...it seems possible that certain individuals have some alteration of their connective tissues that causes these tissues to respond in an abnormal manner ...to microruptures". http://www.dupuytrenfoundation.org/DupPDFs/1960_Larsen_1088.pdf

Friday, December 11, 2009

What's old is new in Dupuytren's

Larsen's insightful study and review of the demographics and microscopic anatomy of Dupuytren's disease is over 50 years old, but reads like a recent publication. The author describes and ponders the significance of topics which were well known at the time: perivascular inflammation adjacent to but not within the affected areas; iron pigment in the center of active nodules. Non operative treatment with enzyme injections, nutritional supplements, radiotherapy are all discussed. Fasciotomy, fasciectomy and dermofasciectomy with skin graft are described and compared as are problems of postoperative stiffness and recurrence. Koch, Bruner, Boyes and Meyerding all comment. Fascinating, clear and delightful. http://www.dupuytrenfoundation.org/DupPDFs/1958_Larsen.pdf

Thursday, December 10, 2009

Nice Overview of Dupuytren's

Time to pause and look at the big picture. Here is a balanced overview of the history, biology, etiology and epidemiology of Dupuytren's Disease: http://www.dupuytrenfoundation.org/DupPDFs/2003_Thurston.pdf

Wednesday, December 9, 2009

The potential of cryotherapy and Dupuytren's

Myofibroblasts are part of the normal tissue repair response to almost all injuries: cut, crush, burn, chemical injury, infectious gangrene, and others - with one exception: freeze injury. Freeze burns don't contract, possibly because only in freeze injury, the original collagen matrix scaffold is preserved, which may inhibit myofibroblast formation: http://www.dupuytrenfoundation.org/DupPDFs/1984_Ehrlich.pdf. This makes cryotherapy a potential treatment for Dupuytren's related nodules: it might just turn the process off. The problem is how to precisely control the extent of freeze injury: freeze both finger arteries, no more finger. The anatomy of foot involvement is different than the hand, and there is some experience with treating Dupuytren's half-brother, Ledderhose, with cryotherapy. It looks encouraging: http://www.dupuytrenfoundation.org/DupPDFs/2005_Goldstein.pdf.

Tuesday, December 8, 2009

Is Dupuytren's work related?

A specific gene has not been definitively associated with Dupuytren's, but the best evidence suggests that the primary cause is genetic. There are factors which alter risk, such as diabetes and local trauma, but these are minor compared with the underlying genetic risk. The question of causation is not simply academic: since the time of Dupuytren, lawsuits have been filed to claim payment for Dupuytren's Disease as a work-related injury. Unlike the laws of Man, the laws of Nature are not altered by argument, but the courts continue to debate the issue, as shown in this recent court document: http://www.dupuytrenfoundation.org/DupPDFs/2008_Bridgett.pdf

Sunday, December 6, 2009

Vitamin E treatment of Dupuytren's Contracture

Treating Dupuytren's with vitamin E. Does it work? No, according to this 50 year old study, documenting results with before and after plaster casts of the bent fingers. The results: no improvement in the degree of contracture. This is a pretty straightforward clearly documented study, which answers the question "Does three months of vitamin E therapy help straighten fingers bent by Dupuytren's?" Apparently not. It doesn't answer the much more difficult question "Does vitamin E therapy prevent progression of Dupuytren's contracture?". I'd still like to know: http://www.DupuytrenFoundation.org/DupPDFs/1952_Richards_1269.pdf

Saturday, December 5, 2009

Not your typical Viking's Dupuytren's

In the Viking era, boats from what is now Denmark travelled west across the North Sea to invade what is now Great Britain, but boats from what is now Sweden travelled south across the Baltic Sea and took rivers deep into what is now southern Europe, where they may have left a genetic trail. This southern European survey shows that the prevalence of Dupuytren's in Bosnia and Herzegovina is higher than one might expect, with a somewhat different age distribution compared to surveys of northern Europe, and the novel finding of a predominance of right hand involvement: http://www.dupuytrenfoundation.org/DupPDFs/2004_Zerajic_1030.pdf

Friday, December 4, 2009

Cell biology and faulty brakes in Dupuytren's

TGF-beta is a protein which lets some cells boss other cells around. It's manufactured and released by some cells, and other cells change what they are doing when they notice that TGF-beta is around. TGF-beta does different things to different cells, always in a domino effect. For example, fibroblasts respond to TGF-beta by accumulating the protein beta-catenin inside the cells, which then triggers another protein, TCF/LEF, inside the cell nucleus to turn on certain genes which then change what that cell does and looks like. See? Dominos. This study reveals an automatic braking system: Normally, TGF-beta triggers fibroblasts to make collagen, and then that collagen steps on the brakes by blocking TGF-beta. This study suggests how this braking system may be broken in Dupuytren's: Not only are Dupuytren's fibroblasts more sensitive to TGF-beta than regular fibroblasts, but Dupuytren fibroblasts manufacture a different mix of collagen (type 1 and type 3) than normal fibroblasts (only type 1), which may not have the same regulatory effect. More studies are in the works - very exciting! http://www.dupuytrenfoundation.org/DupPDFs/2009_Vi.pdf

Thursday, December 3, 2009

Oxygen Free Radicals and Dupuytren's

Oxygen free radicals affect Dupuytren's fibroblasts: high levels are toxic, but not only do slightly elevated levels stimulate fibroblast activity, active fibroblasts actually produce oxygen free radicals. Which is the chicken and and which is the egg? This seminal paper reports studies of the effects of oxygen free radicals on Dupuytren and normal fibroblasts, the effect of blocking free radicals with free radical scavengers, and brings up the relationship between mechanical forces, oxygen free radicals and abnormal fibroblast proliferation in Dupuytren's: http://www.dupuytrenfoundation.org/DupPDFs/1990_Murrell_1203.pdf. Cause and effect? We still need to know - more work to do.

Wednesday, December 2, 2009

Viking blood, blue eyes and other risk factors for Dupuytren's

What is the actual story of the Vikings and Dupuytren's? The full history will never be known, but some fascinating details on this and other risk factors, including blue eyes, are reviewed here: http://www.dupuytrenfoundation.org/DupPDFs/2001_Flatt_1397.pdf. See page 4 for a decision tree showing how to predict the risk of recurrence after surgery based on family history, bilaterality, age of onset and involvement of other areas.

Tuesday, December 1, 2009

Sorting out the truth

Don't believe everything you read about Dupuytren's - even in respectable journals. I was aware that reflex sympathetic dystrophy (complex regional pain syndrome) was more common after fasciectomy for Dupuytren's than for other hand operations, but there is little published on this. Then, this report came out documenting surprisingly high incidence of this complication, higher than I would have guessed: http://www.dupuytrenfoundation.org/DupPDFs/2006_Reuben_499.pdf. Sadly, the lead author on this and several other academic papers was found to have falsified data, and the accuracy of this particular report will never be known. Too bad - I'd still like to know what the actual numbers were.