Collagenase for Ledderhose?

I have previously covered the topic of Collagenase injections by looking at various aspects of it including its use in cells, interviewing a Doctor that uses it for Dupuytren's and covering the material presented at the Dupuytren's symposium. Because it has not been approved for Ledderhose I don't have a specific page in detail on the treatments page. 

There are a couple of different enzymes that have been trialled to break down these lumps and it looks like Endo are hoping that their product can be an option for Ledderhose. 

Endo Presents New Investigational Collagenase Clostridium Histolyticum Data at the American Podiatric Medical Association Annual Scientific Meeting

So what does the article actually say? 

That there have been some encouraging clinical trials done on using CCH in the treatment of Ledderhose disease. Basically so far their studies are indicating that the injections are well tolerated by the majority of patients and that most are seeing an improvement in the condition. Overall it sounds promising but obviously they are still looking into it and I know there have been mixed experiences with using it to treat Dupuytren's. 

Would be good to have another treatment for Ledderhose, of course assuming that is a successful and viable soltiion. 

Update to Dr Davis Interview

Not that long ago now I did an interview with Dr Eddie Davis on the use of Hyaluronidase, this is an enzyme that specifically acts to reduce scar tissue in a similar fashion to collagenase. It appears that this has drawn the interest of many patients. I am already in discussions with one patient that has now had the the treatment and hopefully then will soon be providing answers to some interview questions. Another patient has seen the interview and decided they would like to know more, so they asked Dr Davis some questions and posted the results on the International Dupuytren's Society forum and have kindly allowed me to share them on here. 

Please see the interview here and scroll down to find the new questions and answers. It would be great if there was a published medical article on this treatment as it appears that the results are good for patients but many people, especially other medical professionals, would like to see some proof that the treatment works for the condition before the consider using it themselves. 

I do have some other Ledderhose news but I will wait for it to be more formalised before I consider posting another about it. There will also hopefully be a few more interviews on the way. 

Don't forget if you want to be interviews, point out a mistake or have a suggestion then please get in touch as I want to do all I can to make this site as useful as possible. 

An updated Ledderhose story

I thought that it was about time that I updated my story, so here is the whole story, the old stuff is in blue and the new stuff is at the end in black. I have removed some of the details that were in the original post about the science and things as I have now covered that in much more details. For the original post see here.


Plantar Fibroma and my experience: 


This is a relatively unknown disease that can be painful and debilitating; here I am going to tell you my story and as yet unsuccessful attempts to alleviate the problem. 


Growing up I was sure I had a little bump in the arch of my foot but there was no pain, no growth and nothing to be concerned about, then two years ago out of nowhere like the little menace that it is it started to grow and started to become really painful. I headed off to the doctors as it was starting to interrupt with my daily life and this was not good enough. My GP has a look at the lump and annoyingly decided that it needed to be prodded which of course just made it more painful, he then informed me of what I already expected that it was probably a plantar fibroma. A plantar fibroma is a benign tumour that forms in the arch of your foot. I think a good way of thinking of it is basically that you have a marble stuck in the middle of the arch of your foot and it is like stepping on that all day. 


Being a research scientist I was intrigued to see what I could find out about this nasty little thing, so I did some online searches using both just Google but also Pubmed to look for research articles on the condition. Now this was a few years ago so I can't remember all of the details but basically I found that Physio can't help, surgery can't help as it just grows back most of the time, steroid injections might help but might make it worse and that there are several other types of treatment but that are not available in the UK. So after my research I was quite surprised when the doctor referred me for Physio.... I waited for an appointment and then I waited some more, I was in so much pain that I decided, as my parents said they'd pay, for me to go to a private Physio. I went along and explained what I had, she was very experienced and very helpful, but said that in all of her years she had only come across one other case and that there is no known way for physio to help the condition. Being skint I needed to see the NHS physio before being put through to the foot specialist, luckily I got one pretty quickly after the above as I said I was happy to see a student physio, they told me the same thing as the private one and sent me on my way. I did learn from the private physio that it would be best to invest in a good pair of running trainers and wear them all the time and this did help decrease the pain to some degree. 


I was getting pretty stressed at this point, my foot was killing me, there wasn't and if I am honest still isn't really a step in the day where I don't feel it, and many times I can just be lying in bed and it will twinge and I'll be in a lot of pain for 30 seconds or so. Anyway I was finally going to see the foot specialist to get answers. I went along and they said pretty much what I already knew, if I was to have surgery (let's face it if you hear tumour you do think surgery) the chances of it growing back are very very high and in all likelihood it is going to come back faster and harder and meaner and it really is a last resort, they were nice however and said that maybe at this point the best option would be to try an ultrasound guided steroid injection into the fibroma. 


A few months later with little progress in any way I was lying on a bed waiting for the injection, I had been told that I would require local anaesthetic otherwise the injection would be incredibly painful, well the local was really really painful but the steroid injection just felt like some liquid surrounding the lump. I was told to avoid sport for a few weeks but otherwise I should be ok, well I stupidly decided to head off to the lab, not realising that I was only pain free because of the local, a few hours later that wore off and I was in a lot of pain and couldn't walk and had to be picked up and taken home. 


Around the same time as this I started to do a lot of cycling, with my weight being a potential issue and pretty much any other form of exercise out of the question due to the foot pain and it was working I began to lose weight. Now whether it was the weight loss or whether it was the steroid injection that helped I don't know but over the coming months the pain began to subside, I was able to thrash everyone at badminton again but still in the knowledge that the lump was there it was just more in the background. 


Things were good for nearly a year and then it all started again, I started to get increasing pain in my foot, increasing twinges and more and more depressed about it. A few things had changed over that year, I was no longer living with my parents but was living with my fiancé, whilst this is of course amazing it does mean I don't really have easy access to cycling and it turned out I had to be rereferred to the specialist as I had been discharged, then my referral wasn't received and I have an appointment in December. 


The pain now is at a point where I can't give a 20minute presentation without requiring a seat, not only that but the condition has progressed to the point where if I have had a busy day on my feet I cannot bend the toes on my left foot up as the tendon in the bottom of my foot where the lump is located becomes too tight. 


The problem with this thing is that I now don't walk properly, my foot is twisted so that I walk on the outside of my foot to stop weight from going through the lump, whilst this is a good thing it causes other pains as this is not how we evolved to walk. I think as a result of this and increased weight bearing on the other leg I now have Achilles tendonopathy (or tendonitis depending on who you see) which means I now have problems in both legs, luckily the Physio can help with the ankle and it seems to be working (but that's another story). 

Right so onto the new stuff. So not that long after I made the above I made the trip back to the specialist and whilst the appointment was not that great as the guy was very unhelpful and was even suggesting that I may have something different I was then sent for both an MRI to confirm the diagnosis and also for orthotics to see if they could help my condition. 

So firstly onto the orthotics. The appointment for this was really good and the guy seemed to know what he was talking about and I had all the prep done and they were sent off to be made. I was quite optimistic about these for several reasons. The signs were good as the best trainers for me were the ones with most support which prior to getting the Orthotics were running trainers. The running trainers are great but they are not warm in the winter, not dry in the winter and are very expensive when you are wearing them all day every day. The orthotics arrived and I instantly took to them, I was ill with the flu at the time so managed to wear them in gradually although still quicker than recommended. At first these seemed to help but also coincided with me spending less time and with my wedding and honeymoon which of course was the most wonderful and relaxing 2 weeks of my life. 

In the few weeks since I have been back from the honeymoon the foot pain has intensified and I am starting to reach the edge of my limit and I either have to choose to have an unproductive day and risk not finishing my PhD or have a productive day and be in pain that I am not going to be able to cope with for the remainder and this is kind of the dilemma I find myself in at the moment. 

Right though back to the MRI. Not much to say about the MRI. The actual process was very simple and easy, I went along and stuck my foot in a machine and then waited a couple of weeks for an appointment to discuss it with the foot specialist. This appointment was much more successful that the first but was with the boss rather than one of the not so clever people. The man had lots of interesting points but was told that until I basically cannot walk that surgery is not an option but it remains my only option. But the MRI did confirm that it was Ledderhose disease so at least we knew what we were tackling. 

In the past 6 months or so since I made this post lots has happened and not just me getting married and my foot getting worse. I am also much more open about my foot with lots of people and I am getting lots more support from my wife, my family, my in-laws and my friends (you all know who you are). This has led to me seeking new ideas and new hope as to where I should go next. 

For starts I now have a foot spa and heated slippers which help ease the pain for a short time but that is better than nothing. I have a stall for the kitchen which helps me keep up with the house work and a walking stick for when it gets really bad. All these things help but do not take away the immense pain that I feel in my foot. This pain sometimes comes first thing and is normally present by midday and always there by 3pm and is really excruciating at the moment. 

I no longer feel that I am a one lump person. I am getting a lot of pain down near my toes on my left foot and I am worried that there maybe a lump at the base of my second toe as this area in particular is very tender to the touch. I also think I am developing the same problem in my right foot, I have started to get the occasional pain that I got when it all started in my right foot and am worried that it is now bilateral. 

This has led to me looking into lots of different treatment options and there are others out there that are not on the NHS. I am currently looking in radiotherapy as my next choice as I have interviewed several patients that have had success with this option and also have been looking at Xiapex which appears to be coming to the UK (in Devon for Dupuytren's at least). 

So I guess at the moment I am in a job that makes my foot very painful as there is lots of standing and I am in a place where my next treatment is either going to have to be costly due to the NHS not providing it or surgery which I have been told to avoid by so many people I hardly consider it an option.

Can scar formation be used as a useful model for Ledderhose and Dupuytren's?

My News: 

So today my foot was hurting from about 11am onwards which is a new early start record for me, yey. Consistent with this when I had to walk for 5 minutes my foot was really hurting, I was limping quite bad and grimacing and all that malarkey but luckily today I managed to get a spot on the train and the bus. The pain however was bad enough that I thought I should look into seeing about getting a folding walking stick, that way I can have it on me and use it when I need to take the pressure off of my foot, sure it is not ideal and I will have to get over the sense of annoyance and to some extent embarrassment at having to use one but if I need to that I need to.... still bet I couldn't get a disabled badge for the car even though you see people using those spaces all of the time and there are always people on yellow lines that think it is ok because the other car did it when the other car actually had a disabled badge. 

Onto the scar formation thing that I wanted to talk about today. Must say that I am going to be really naughty and use wikipedia as a source of information, this is really bad but the page seems to be well sourced so I don't feel too bad using it. 

Introduction to scars and why they are important in understanding Dupuytren's disease (DD) and Ledderhose Disease (LD):  

So basically the reason for this post is, as many of you will know, that the formation of DD and LD nodules is thought (in some cases at least) to be caused by an over response to trauma and is essential scar tissue and this is why when you cut it away it often comes back as surgery gives it plenty of scar tissue to initiate from. So of course if it can be understood how normal scar tissue is formed and regulated and indeed how we can stop the formation of scar tissue in cases where it is extreme or undesirable then this may help find a way to combat LD and DD. 

Scars are basically a type of fibrous tissue that takes the place of normal tissue after trauma, the tissue in question is not always the skin although this is the most obvious place of scarring both visually and in terms of frequency. In fact some animals are actually capable of regeneration of tissue rather than scar formation and indeed this is an area of research where I am sure a lot of work is being done. 

The main components of both skin and scar tissue is collagen (those familiar with LD and DD will probably know about collagen as it is the main part of the lumps) but the difference between the 2 is in the way that it is put together as skin is normally random and scar tissue will repair in an organised fashion. Over expression of collagen in scars can lead to raised scars or keloids and of course over expression in other places can lead to DD and LD. 

The normal cells that are in the skin are fibroblasts and for the purposes of scar formation they are transformed (that IS a scientific term and I don't mean transformed by magic) into myofibroblasts which are more capable of mass producing collagen. I have tried to avoid going into cell types in my recent reviews of scientific papers but the cells that are the main components of DD and LD nodules are myofibroblasts that have come from fibroblasts. 

There are actually several treatments for scarring, that is to say that when it is going to be bad (to the extreme) there are things that are done to try to prevent it and some of these jumped out at me. The first one is radiation, much like in LD and DD this is used to limited effect to try and stop development of the scar but is only used in really bad cases as of course radiation means increased cancer risk. The other one that made my notes was steroid injections which again are used in the treatment of LD and DD. Also they noted that vitamin E was tried but didn't work (just like LD and DD). 

So it is clear that scarring can be used in some ways as a model for LD and DD and if a treatment or something is found that helps to prevent scarring then maybe it can be used in LD and DD.

Signalling wise I can add another link in my diagram as TGF-B1 is known to be increased after damage so now we have.... (and I am finishing with this picture)