News, results and another survey

Recent weeks have been very interesting. Although I have not posted many blog posts or particularly had many page-views I have been fairly active. Instead of my usual activities I have been trying to raise awareness, this is not something that is easy to do for a rare non-life-threatening condition however I have had some success.

I have had interest from 2 local papers, one is hopefully going to publish an article this week and the other one I will contact again once we have had sufficient time to see if a Dupuytren’s patient that has had Xiapex can be found. The other development is that I had BBC over to interview me yesterday and they are going to run a piece on BBC South East today, including an interview with Dr Shaffer and this may then lead to a post on the BBC website. How amazing would it be to have an article on Ledderhose on the BBC website potentially linking to this blog and Dr Shaffer’s website? They did make clear that this is only a maybe but that is still a better situation that we were in last week.

Hopefully the media exposure will not stop there and I can use this momentum to try and get something out there that doesn't just cover the South-East, any ideas or contact you have are of course welcome.

Don’t forget that the deadline for submission of patient information for the survey is fast approaching and if you haven’t already filled it out it would be great to have as many responses as possible.  esurv.org/?u=dupled 

I am still collected results for the following mini-surveys as well, it would be great to have more information on these to get a better understanding of any significance or not in the results:

Plantar Fibroma and Plantar Fasciitis

Actually look like that is the only one as the initial look into the blood types showed no real difference and doesn't look like it warrants further investigation.

Preliminary results from the large survey appear to indicate that Dupuytren’s, as expected has a higher incidence in men but conversely Ledderhose has a higher incidence in women (or at least more women with Ledderhose have responded). This doesn't surprise me as I have probably been contact by more women than men however it does give rise to an interesting questions, why?

I can’t remember the exact figures but it was something like 55:45 men women for DD and vice versa for Ledderhose, numbers this close suggest to me that it is not likely to be the genetic element that plays a role meaning it could be environmental.

Graph outline the total percentage of male and female respondents with either DD or LD

The classic example here would be trauma, in men the example is that the hands are injured during manual labour and careers such as working in a mine or using the large power drills are thought to have an impact, some people have even noted a high level of musicians in Dupuytren’s patients. So what could be causing this for Ledderhose that provides an increased risk to women?

I have tried to think outside of the obvious and I am willing to have suggestions however the only thing that came to mind was that women almost exclusively wear high heels and perhaps his could account for the difference. After all we are only looking for something to account for the 10% difference in Dupuytren’s, so it could be that (purely hypothetical numbers) 80% of Dupuytren’s and Ledderhose patients are not caused by trauma and therefore you have 40% women and 40% man. In the remaining 20% we then see the difference, where for Dupuytren’s trauma is more likely in a man so this leads to the 55:45 split in favour of men whilst in Ledderhose trauma to the foot is more likely in women so you get the 55:45 split in favour of women. Something that can be discussed much more in the future when all results are in however I would love to start asking patients whether they have had any trauma etc to see whether can find any relevance.

So here is a short survey so that we can look at this

Entries are also still open for the blog awards, you can vote for me here.

Progress on the Ledderhose disease patient guide is slow going, for some treatments I am still trying to get more people, mainly surgeons, involved but I am hoping that the end of next year is a realistic target if I find time to really get my teeth into it. 

I am currently collecting the results of the patient series for this month and hopefully will have them all ready for the weekend so I can share how everyone else is getting. 

Hope every one is finding something that helps their feet, for those in the UK be sure to keep your feet warm for the winter, I always find the cold makes it hurt that little but more. 

Progression of Ledderhose disease

Below is some information that a visitor to the blog felt was missing. They said they had some information on it and they were happy to write it up. All information is posted with their permission, in fact they wrote it for the purpose of me posting it. 

It is true that I do not have much information on the progression of the disease, this is partly because, as you can see below, there is not a huge amount of information out there and secondly because I started the blog looking at treatments as that was the stage as I was. So for all of those that are new to the condition you may find the information below interesting to read. I felt that the paragraphs below were not enough to warrant a complete post so I conducted a small survey to complement the information. 

There is very little statistical information on the potential progression of Ledderhose Disease (LD)/Plantar Fibroma (PF).  There are individual disease trajectories provided by individuals on various patient forums. These patient histories can not be properly weighed as indicative of the normal course of the disease because there is no broad sampling of patients, no regular follow up, no quantitative measurements.  Therefore, the reader does not know if these patients are outliers or the norm.  In addition, there may be completely fabricated patient histories that have been authored by unscrupulous people preying on the fear and desperation of patients to sell their products.

The most rigorous published scientific studies that I have found on the LD have been performed by German researchers who were investigating the effectiveness of radiation therapy on Dupuytren's Disease (DD) and Ledderhose Disease(LD).  What is of most value in these studies is their use of a control (untreated) population.  For example, Seegenschmiedt[1] reported that for a control patient population of 47 people with 67 affected feet with minimal symptoms, 6 year average time of observation, minimum observation time of 1 year, 10 feet (15%) had a spontaneous remission, 34 feet (51%) remained stable, and 23 feet (34%) progressed and required treatment.  

These data are quite remarkable as they indicates that for a large percentage of LD patients  (66%), the expected disease trajectory is stability or regression for a non trivial period.  

I wanted to complement this information with anything extra that I could find, this included information from a patient that contacted me around that time. They suffered from Ledderhose and despite having nodules bigger than mine they did not experience pain. I do think that up to a certain point the size of the nodule is not the problem, it is the location and depth under the skin and whether it hits a nerve. Once it protrudes significantly out of the sole of the foot this can then cause issues based on the size of the lump (that is all just my opinion and thoughts but is based on the size of the fibroma not necessarily being related to the pain caused, which as it turns out is the case in the survey).

In order to gather more information on this I conducted a small survey which revealed some interesting results. 

Participants were asked to rank from 1 to 10 (10 being most painful) their condition from year 0 (diagnosis) up until now or year 30 (only 1 participant had had the condition for 30 years). Below I have 2 tables showing some of the results. 

Change	Num Occurrences	Comment
-10	0
-9	0
-8	1	*Year after RT treatment, no later pain increase
-7	0
-6	1	*Year after RT treatment, no later pain increase
-5	3	*all 3 after surgery and again increased
-4	0
-3	1
-2	3
-1	14
0	107
1	55	*High number of 0/1/ 2 suggest that progression is normally slow
2	19
3	7
4	7
5	3
6	3	*But over 1/2 of respondents experience a sharp increase
7	1
8	0
9	1
10	1

Table 1: Column 1 shows the change from the previous year, column 2 shows the number of years in which this change occurred and the third column shows a comment. Colouring is used to group results together.

Avg Max pain
2.28	Max yr on yr diff 2
7.22	> 3 year on year diff

Table 2: The average max pain for patients split by those that report a max change year on year of 2 and those that reporting having a change of greater than 2.

Table 1 shows that in most cases year on year there is little change in the condition however 50% of patients experience at least one year where there is an increase of 3 or more. When used in conjunction with table 2 this shows that those patients that experience a large jump are more likely to have significant pain. I have not calculated a number to show this but this is not simply due to an increase in the number of years a patient has the condition but it is that those with high levels have pain have had a large jump and not a gradual increase. In fact with only 1 exception the highest pain level reached by someone someone without a large jump was 3 (the exception being level 8).

Several patients report large decreases in pain, the 2 largest pain decreases were both as a result of radiotherapy. There were 3 patients that report a minus 5 in pain, all of these were because of surgery but in all 3 cases the pain then rose again. In no patients did the condition naturally regress year on year by a significant amount when there was no treatment involved. 

The above information and the rest of the results are summarised below. 

•  The size of the nodule is not proportional to the amount of pain
• Age of onset does not impact on progression
• Male or Female does not impact on progression
• Generally when gets bad seems to progress quickly
• It appears that without a large increase in pain you are not like to be experiencing too much pain
• Significant decreases have been observed post treatment with radiotherapy and surgery, after surgery pain rose again.

Of course to get these results I arbitrarily chose a jump of 3 as being large. I did chose this before analysing any data to try and avoid bias. Also this survey did not have many answers as it was just an initial survey which may help in the future development of a more comprehensive survey on the subject or a database to collect patient information. The results in the summary are all results which were clear from looking at the data and no numbers or graphs have been provided but I can make upon request. 

Below are some examples of patients pain levels over time. 

(1) Radiotherapy for primary or recurrent morbus ledderhose: 12 year long-term outcome of a prospective phase 2 trial. M. Heinrich Seegenschmiedt, Etienne Hanslian, Mark Wielpütz

Interview with DD and LD patient treated with Tissue Plasminogen Activators for LD

Today I have an interview with a patient from Australia. This patient has had an injection of tissue plasminogen activators from Dr Chin. The results for this patient are very good and I am lucky enough to have a very comprehensive interview with this patient. 

1. Do you suffer from Ledderhose and or Dupuytren's?

Both  - in both feet and both hands

2. Do you have a family history of the conditions? Or fall under any of the risk factors? 

Ex-smoker from age 12 stopped at age 40 moderate alcohol, hit it hard like most teenagers when in the British Army, Mum had DD, no one else in family seems to have it, 4 siblings and to the best of my knowledge no immediate family (Nephews/Nieces/Cousins) show any signs

3. Where are you based, how old are you and how long have you been suffering with the condition and how has it developed over time?

Now living in Redcliffe, north of Brisbane in Queensland Australia.  Aged 60 and 7 months.  First recollection I had DD which appeared first on my left hand was around 20 years ago followed shortly by LH on my feet.

The left hand and feet started first followed shortly by the right hand and foot.

4. What treatment options have you had?

Left Hand

5 Needle Aponeurotomy 3 in USA with Dr Eaton and two releases locally in Australia.

1 partial strip to release the very badly swollen ring finger knuckle, which has kept the finger straight for 10 months now, but some nerve damage.

Right Hand

3 Needle Aponeurotomy in USA with Dr Eaton  The ring finger on the Right hand is starting to get to about 15 degrees but it is also twisted and the knuckle is swelling so may look to a release soon.

Left Foot

Tissue Plasminogen Activators injection at the same time as my left hand was operated on (under General anaesthetic).

5. You have been treated with Tissue Plasminogen Activators, could you please explain how you found out about this treatment and why you picked it over other treatment options?

I was informed of Dr. Chin from a contact I met at a meeting and followed up.  The Colleague was very enthusiastic about it as he was a Biotechnology Consultant who was working with Dr. Chin and had seen the results.

I was privy to some commercially sensitive information regarding the treatment and its efficacy and the path Dr. Chin was taking and decided it was safe enough to try particularly as it is below any dose given for other clinical reasons for which it is approved.

I have studied the results of other treatments and apart from some success with RT could not see anything that was successful.  I did attend an RT clinic here in Brisbane but was not convinced they had the experience at that point.

Dr. Chin has treated in excess of 100 patients for Ledderhose and I am unsure how many for DD.  He has stated that for Ledderhose after 10 years plus there has been no recurrence, but for DD recurrence has occurred in some patients after 5 years.

There are no significant side effects that have been reported, there is a very small chance of temporary impotence.

6. Please describe, in as much details as possible, the procedure to administer the treatment and the recovery period?

The injections were made into each nodule in the foot, (I think he missed one).  For me it was under anaesthetic as I was having the DD treated, but normally done with a local anaesthetic.

Pretty sore for two days, walking on the outside of the foot.

The foot settled after 3 days then the nodules started to immediately shrink.  Massaging was indicated for helping the TPA work in the nodule.

I was warned the top of the foot would hurt after 3 - 5 weeks, Dr Chin said this is because the foot will flatten and muscles and tendons would be stretched that had been contracted and sure after about 4 weeks that is what happened.  The pain lasted about a week and since then has not been a problem.

7. How has your condition progressed since you had the treatment and are you happy with it?

Some 10 months later there is one very small nodule on the left foot that has been there since the injection (I think this is the one he missed).  Cramping has greatly reduced in my left leg!  There is no sign of the original nodules so I would call this treatment a success.  I will be going to Dr Chin possibly early in 2104 to get my right foot treated.

8. Is there any more information you would like to share with the patient community?

My experience is a positive one, perhaps I have been lucky but TPA is striking at the very core of the tissue mass and has been utilised for heart attack victims for many years to break up clots.  Dr. Chin is attempting to license the treatment to recover the cost of his research to date, I hope he gets a sponsor and makes this treatment more available.  Some of the photos he showed me of before and after have been spectacular so I feel it is a worthwhile treatment to pursue.

It certainly is a very interesting treatment option and not one that I am aware of being used anywhere other than by Dr Chin (probably because he has a patent). Hopefully there will be a publication soon that show all the results, if they truly are 100% for Ledderhose then that is really very remarkable and perhaps this option can become more mainstream in the future. 

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. 

Verapamil for treatment of Ledderhose Disease and related disorders

Verapamil gel for the treatment of Plantar Fibromas / Plantar Fibromatosis / Ledderhose Disease:

After my interview with Petricd I said I would do a post on Verapamil gel and so here it is. This is a gel which you rub on to the lump. It is advertised as for use with Dupuytren's and Ledderhose and a good place to go for information (albeit a place that is trying to sell the stuff) is pdlabs (1a).

How and why does Verapamil gel help a plantar fibroma / ledderhose disease?: 

Right so this is the bit where a little bit of research is required. I figure that a good place to start is the pdlabs website and for the purposes of this post I went to the Ledderhose disease section (1b). Here they explain that the nodules that form in Ledderhose disease or indeed Dupuytren's contracture are mainly caused by an excess of collagen and that one of the requirements for collagen production is calcium and that verapamil works as it is a calcium channel blocker. The idea is that in cells you have a battle between the production of collagen and the breakdown of collagen and in the disease cells the battle is being won by collagen production so it builds up but by adding in verapamil you reduce the levels of collagen production and turn the course of the war in the favour of collagen breakdown which it then ideally wins by breaking down the lump or they reach a stalemate by at least stopping progression. 

Results?: 

This is where is gets a bit tricky. So to start with I have referred to the book Dupuytren's Disease and related hyperproliferative disorders (2). They say that this is still a work in progress but that the reports that have been generated so far by users on the Dupuytren's online forum suggest that it does not work very well. A very good thread to look at here is this one. Some of the comments that members have are quite harsh and it makes you wonder about the validity of the results PDlabs say they have below. Anyway here are some quotes from the thread I have linked to above: 

Randy H - "Contact the folks at PD labs and ask for any published studies on the product for your particular usage. I doubt they have anything. I tried it anyway........with no results." 

Bruce - " ...it is a complete waste of money and time. These guys should be shut down for deception."

JimH- "It does nothing. Ask your MD what information he has regarding its effectiveness and I'll bet he admits he has none."

Debrr - "Just to let you know I gave up on verapamil. Overall, didn't seem to do anything for me."

If you have a look round the forum most of the reviews by members that have Dupuytren's, Ledderhose or both are negative but still on to the other side of things.

So what do PDlabs say? Well they say that you need to be using this for 6-12 months and that those that are experience pain find that this is the first thing to disappear and that this usually happens within 90 days. They say that they are in the middle of clinical trials and that they are so far going very, see this page for details but to summarise they say that 100% of patients are experiencing a decrease in pain and most are having a decrease in size as well. 

Side Effects: 

As far as I am aware there are no side effects to using this on your feet, however it is also in use (though not for LD/DD treatment) in the form of a tablet which does have some side effects but I won't put them here as they might confuse things. 

Experience: 

I have had no experience with this but I have come across several posts on the Dupuytren's online forum but most of the people that have had this treatment have not got back to me. The one person that has though is the one that I mentioned earlier, Petricd, whom has had some success with verapamil on their Ledderhose but not their Dupuytren's. 

References: 

(1a) - http://pdlabs.net - Site accessed 07/04/2012 - a provider of Verapamil.
(1b) -http://pdlabs.net/plantar_fibromatosis/whatIsTvGel_plantar.html
(2) Dupuytren’s Disease and Related Hyperproliferative Disorders, Principles, Research, and Clinical Perspectives Eaton, C.; Seegenschmiedt, M.H.; Bayat, A.; Gabbiani, G.; Werker, P.; Wach, W. (Eds.) 2012.