Okay, last lecture of the day, Dupuytren's disease. We all take care of Dupuytren's disease. We're comfortable with it. So I want to just get you some high yield facts because this is something that is tested quite often on both the self-assessment exam and having taken the recertification exam a few years ago on the research quite a bit. So high yield facts were going to be marked with a star, and I'll go over them. So the genetics of Dupuytren's disease, it's a progressive disease. We all know that. There's a clear genetic predisposition, which is prevalent in European white males. It's thought to have originated from the Germanic tribes around 1200 BC and spread by tribal migration including Viking conquest. It's quite rare in the Middle East, Asian descent and African descent. I live in Los Angeles. I see it quite often in people from Mexican descent, and that was surprising to me. But there's a lot of European intermingling from all the conquests for the Mexicans. It's autosomal dominant with variable penetrance. Siblings of patients are three times more likely to develop Dupuytren's disease, and there's no single polymorphism that's been identified or group of genes that have been identified that are responsible for it. So pathophysiology. This one's really important. It's myofibroblast. What causes Dupuytren's disease? It's myofibroblast. So there's myofibroblast proliferation. This shows up over and over again. The second thing that's involved in Dupuytren's disease is a conversion of the collagen matrix. There's a conversion from type 1 collagen to type 3 collagen. So normal fascia, as indicated in the left image, consists of 95% type 1 collagen. So it's mainly type 1 collagen, 95% and 5% type 3 collagen. But as Dupuytren's progresses, there's a conversion so that there is a 40% type 3 collagen in Dupuytren's disease. So the fibers become organized. It's not a random pattern just like normal fascia. So it's thought that there's a genetic predisposition with increasing age, male sex, smoking, and a trauma. There's some form of microvascular angiopathy. Ischemia occurs. Free radicals are elaborated. And then there's increase in IL-1. Then there's increase in transforming growth factor beta, EGF, FGF, and platelet-derived growth factor, which results in, again, myofibroblast proliferation, myofibroblast differentiation, contraction of the myofibroblast, and then collagen type 3 production. What's interesting here is IL-1. When you have trauma, there's an increase in IL-1. So I think we've all seen our patients that have maybe hand trauma from a distal radius fracture. They didn't have evidence of Dupuytren's disease before, and then you see them with Dupuytren's disease after the trauma. That's because of IL-1. So this is the slide that I don't like. I've circled and put to the right some of the growth factors and factors that are elaborated that sometimes come up in tests. The ADAM is one of them. The other one is the POSTEN and the TENACEN-C. But the ones that I see most frequently, and I think I saw this on the CAQ exam, was either IL-1, TGF-beta, FGF, or platelet-derived growth factor. Usually they ask about what goes up and not what comes down. But what does come down and downregulated are what's listed here. You may want to just peruse that just right before your exam. And also BMP-4 is downregulated in Dupuytren's disease versus normal tissues. So continuing with pathophysiology, heavy smokers and heavy drinkers, there's an association with it. Diabetics, type 1 diabetics get it more than type 2 diabetics. Male sex, increased age. And then there's a loose association with anti-epileptic medications and manual labor. We know that the anatomy is important, and the anatomy is quite often tested. It has to do with the palmar fascia. And in this image, there's a comparison on the left, which is normal fascia, to the right, which is the diseased Dupuytren's fascia. And I'll show you the changes that occur. The first one is the pre-tendonous band that you see. That changes into the pre-tendonous cord. Next is the natatory ligament. Turns into the natatory cord in Dupuytren's disease. The lateral digital sheet participates in the lateral cord. Grayson's ligament all participates in the spiral cord. And what's spared, and this is a very common question, is Cleland's ligament, and also the transverse fibers of the palmar aponeurosis. That's a gimme question. You're going to see that somewhere coming up. The other one that I see also is what causes a contracture of the web spaces, so that you can't spread the fingers apart. And that's the natatory ligament, which turns into the natatory cord. And finally, another high-yield question is what forms the spiral cord? Well, there's actually four structures that are involved in the spiral cord. The first one is the pre-tendonous cord, the spiral band, lateral digital sheet, and Grayson's ligament. And again, the Cleland's ligament is not part of this. The Cleland's ligament is spared in Dupuytren's disease. The spiral cord does something we all know about it. We watch out for it when we do our operation. It displaces the neurovascular bundles. And the neurovascular bundles are displaced towards the midline, volarly, and also proximally. And in this image where the arrows are, you can see that the digital nerve is right at the center of the digit. Right before I came on Wednesday, I did a case, and I hadn't really seen it this badly. The digital nerve was actually on the contralateral side. It was all the way over there. It looked exactly like the wrong digital nerve. So this is an important slide. This may come up in your exam, so it's one that you want to just quickly look at. What deformity is caused by what cords? So the pre-tendonous cords cause MCP contracture. The natatory cord, as I indicated earlier, causes web space contracture. A spiral one causes neurovascular bundle displacement and MCP and PIP contractures. The central cord causes PIP contracture. The lateral cord is involved in PIP or DIP contractures. And the retrovascular one is the one that's involved in DIP mainly. So that one may come up where they ask which one is involved in DIP contractures. So the clinical presentation is the dupuytrense is more common in males, 1.7 to 1, early on in life. But after 40, it begins to become a one-to-one distribution. Initially you see fibrosis of graphofibers leading to a pitting of the skin and thickening. So you can see the very early pitting in the top image and then the thickening in the below. And then you start having the nodule formations. The myofibroblasts begin to contract. And then they start to convert. The myofibroblasts, as they contract, there's a cellular conversion of... And they become actually acellular. So the cords are relatively acellular collagen matrices. And then you develop the joint contractures as seen here with the MCP and the PIP joints. You can have ectopic disease. Several forms are seen. There's the dupuytrense knuckle pads called Garrod's pads. There's a letterhose disease, which is plantar fibromatosis. And also Peyronie's disease is associated with dupuytrense. So what's dupuytrense diathesis? This may be asked. It's a condition where there's increased severity and recurrence risk of the disease process. Males, onset of age early on, less than 50 years old, bilateral disease, affected siblings and parents, Garrod's pads or Peyronie's disease, and Northern European ancestry. If you have all of these factors, you have a 71% chance of recurrence despite treatment. So this is important in discussions. And I certainly use this in my informed consent process when I see that the diathesis exists. I set the expectations right away that despite any treatment, this is going to either recur or extend. If you have none of these factors, there's only a 23% chance of recurrence. So what are the indications of treatment? This is not something necessarily that may be testable, because it's not agreed upon by everyone. But essentially we say that there's a positive tabletop test and that the patient's not able to place their hand flat on a tabletop with MCP contractures of approximately 30 degrees or more, PIP contractures of 15 to 20 degrees, or if the nodule is large enough that causes them a functional disability. Every patient realizes and they need to know that dupuytrense surgery is palliative. It's not curative. The dupuytrense is a progressive process, and it's important for this type of documentation in your informed consent process. So how do you pick the right treatment option? The treatment options is a difficult one to pick, because every patient is variable. There's even variability within the hand and within the fingers of each hand. The techniques vary, measurements vary, definition of efficacy and recurrence varies in the studies, and the follow-up time of each study varies. So really it's controversial which is the best treatment option, and I don't think you're going to be asked about what treatment option is best for what patient. I think it's safe to say, and most people would agree, that the best treatment option is the one that your surgeon feels most comfortable with. So the procedures are the relatively less invasive needle aponeurotomy, the new kid on the block, which is a collagenase. Then there's the time-tested limited fasciectomy. There's the radical fasciectomy, where you're removing all dupuytrense diseased tissue plus a margin. There was the limited dermatofasciectomy, where you're doing the fasciectomy and excising a small area involved of normal tissues, making it a fire break theory. And then there was the radical dermatofasciectomy, where you're removing all diseased tissues and then full thickness skin grafting. So let's go over some of them. Radical aponeurotomy is a simple technique. You do this under local anesthesia. The local is inserted just into the deep dermis, as you can see on the left image. And then using a 25-gauge needle or a 18-gauge needle, small incisions are placed one to two millimeters long at a one to two centimeter increments along the cord, where you're using a windshield wiper technique of just cutting the diseased cord or just gentle stabs until you weaken it. That's done. Then there's the image above, which shows that the MCP and the PIP joints are hyperextended, and there's a completion rupture of the cord. Skin tears in this procedure are common. Every patient realizes, in my practice certainly, that for every treatment of dupuytrense, skin tears are part and parcel with treatment and are expected. So what are the results of the needle aponeurotomy? Well, the studies vary, but they say that MCP correction is somewhere between 93 and 98 percent in the studies that were looked at. There is a 57 to 67 percent correction of the PIP contractures and a recurrence risk of 35 to 65 percent. Again, you're not going to be asked about the recurrence risks or how much correction you have, because again, it varies so much, and it all depends upon the study that's being looked at. So the new kid on the block that we talked about was Zyaflex. Zyaflex is a collagenase that goes under the trade name Zyaflex. It's a mixture of two purified collagenases, OX1 and OX2. It's produced by the Clostridium histolyticum bacterium, and the two collagenases increase the enzymatic degradation of the collagen. And it preferentially, this is a very important point that's going to be probably tested, is works on type 1 and type 3 collagen, but spares type 4 collagen. It has relatively rapid effect. The complications in the short term are edema and skin tears. There's some patients actually have fairly significant edema. There has been tendon ruptures reported in the earlier studies particularly. So the manufacturer recommends against going past the 4 millimeters distal to the digital crease, the proximal digital crease, in order to prevent this rupture. Long term risk for collagenase is recurrence. So again, I'm going to reiterate it because I really think it's important. Type 4 collagen is least affected. And why it's important is that type 4 collagen is what's mainly found in the basement membranes of the digital nerves, arteries, and veins. So collagen, I think everybody knows how to treat it. The enzyme is injected into the diseased cords. The patient looks like this. They come back after the injection on the image. On the right, they come back either the next day or a few days afterwards. And then there's a completion of the cord rupture. And this is an image of a two-year follow-up of a patient with Dupuytren's release with collagenase. The results of the collagenase were initially reported in the cord studies. You may have heard about these. There's a collagenase option for reduction of Dupuytren's disease. These were randomized placebo-controlled studies where they looked at NP joint contractures of somewhere between 20 to 100 degrees and PIP contractures of 20 to 80 degrees. There was the cord 1 study that was the U.S. study involving 16 U.S. sites. And then the cord 2 was the Australian one. So the results were there was an overall improvement versus placebo of 64% in the cord 1 and 44% at 30 days in the cord 2. And these are pretty strict criteria where they call improvement. It's achieving almost near a full extension to less than 5 degrees. When they looked at the NP joints, the NP joints fared better at 77% and 40% for the PIP joints. The efficacy in a secondary publication was a contracture reduction by about 75% and a recurrence risk in another paper was about 35% overall. So what about the surgical interventions, the more invasive techniques? So the first two were the limited invasive techniques. So the incisions can be standard V to Y, sorry, actually Y to V incisions such as seen in the middle finger. They can be the Brunner standard incision seen in the ring finger or a Z-plasty seen in the small finger on this image. So it's a regional fasciectomy. The incision is made. The skin flaps are elevated. The neurovascular structures are identified and protected and the tendons are identified and protected and everything in between is removed. And the final appearance looks something like on the picture on the bottom right. There's a variation of this technique and this is my preferred technique. This is what I usually use standardly. I've tried everything and I've settled on this. I found that in my practice and in my hands, this has the greatest longevity for patients. It's the limited incision dermatofasciectomy. So it's an open technique with small little transverse incisions that I try to hide in the skin creases. The diseased tissues are identified after you've identified the neurovascular structures. I find it's fairly easy to identify those in the deep tissues. And the below image is a patient just at 10 days following surgery. You can see there's very limited edema. Here's another patient that just came back in clinic so I thought I'd put her picture in for you to see. You can see fairly thick diseased tissues in the MCP region, contracture. The diseased tissue is removed. What can be closed is closed. And this is the patient just two weeks after surgery, full range of motion. And this is her after about three months. So I found that this has significantly less edema than the other treatment options including Xyoflex. So I've settled on this in my patient population. But again, that's not for everyone. You need to feel comfortable with the technique that you use. So the efficacy for the open fasciectomy is about 47 to 94%. You can see that's a huge range. It's a huge range because if you look at the studies, the follow-up time is different. It goes from 18 months to several months up to seven years. Obviously the ones that go out longer, the seven year one is going to have a higher recurrence rate. So the recurrence rate was somewhere between 12 to 73%. So really highly variable. So you can't really draw conclusions on the best treatment option for your patients based on the studies. Secondary surgeries are sometimes required. And in my informed consent process, if I do need to do a secondary operation, I tell them that there's a 10 times greater chance for a neurovascular injury with a secondary operation. And that, some people prefer to do dermatofasciectomies in really severe cases. And what is that? That's somewhat fallen out of favor. But this is one of the patients. On the ring finger, you see that a dermatofasciectomy was performed at an earlier time. And then the thumb was done in this stage. Adjunct treatment options are available as well. And the ones I use frequently is this dynamic extension device for PIP contractures. I found that I don't have great success in patients that have longstanding PIP contractures that are not just from the Dupuytren's cord, but they're also ligamentous contractures that are significant. They have a rapid recurrence rate in my hands, despite my treatment options. So with these, this patient had over about a 95 degree contracture of the PIP joint. I performed a small needle aponeurotomy. And at the same time, I placed this device on. And this is the image at just about six weeks after the procedure. So full flexion and full extension. I find that this allows for stretching of all the soft tissues and gets me a better result than not using it. Other factoids to remember for Dupuytren's disease is that it's okay to perform carpal tunnel releases simultaneously in conjunction with the Dupuytren's. Earlier on, I thought that it may pose significantly more complications, including RSD and flare reaction. And that's not born to be true. And then there's the Dupuytren's flare reaction. This is a testable scenario where you have a patient that you've done a Dupuytren's disease. Initially, they've done well. Then they come back within a week or two weeks later with significant swelling, redness, pain. And that's a Dupuytren's flare reaction. And what they want you to do in this test scenario is provide them appropriate pain control, apply steroids, and then change their range of motion. Not be as aggressive. Change it to a light range of motion rather than an aggressive range of motion. So that was the whirlwind Dupuytren's. I hope that got you some points on the exam. And we'll do questions, and we'll be done for the day.

Dupuytren's disease

hand deformity

genetics

treatment options

collagenase

recurrence rates