CORRECTION: I have had a comment saying this is not collagenase, this is correct, however it is an enzyme (that breaks down another part of the extra-cellular matrix, please see the update at the end as to the discussion that took place between the two doctors and also a link HERE to see a few more details on how the enzyme Dr Davis uses works.
2) How common do you think PF is in the USA? It is supposedly more common in males then females and has been linked to a family history of PF and Dupuytren's, smoking, alcohol consumption and diabetes are these risk factors you see in your patients?
Xiaflex is "collagenase clostridium histolyticum," which is a form of collagenase produced by a bacteria, Clostridium histolyticum. Clostridium histolyticum is a bacteria that can cause severe infections including gas gangrene in humans. The features that make this bacteria dangerous are utilized, in part, to a certain benefit. The bacteria can spread through tissues rapidly by dissolving tissues via proteinase enzymes and collagenase enzymes. Isolation of that form of collagenase yields the effective ingredient in Xiaflex which is used to break down excessive collagen in a controlled fashion. Xiaflex is officially indicated by the FDA for Dupuytrens contracture only in the US. It could be used in an "off label" fashion for plantar fibromatosis but there is no compelling reason to do so as there is no evidence that it is superior to other forms of collagenase utilized over the last few decades. It would be significantly more expensive due to its' patent and third party coverage likely to be denied due to off label use.
Our criteria for Vitrase injections is based on the presence of painful lesions of plantar fibromatosis. It has probably been more than 15 years since I have treated the lesions surgically due to the high recurrence rate with surgery and high success rated with hyaluronidase injections.
5) What is your success rate using this treatment? Due you often use multiple injections? And are there any side effects?
I would place our success rate at about 95%. I am only aware of two patients for whom this did not work in the last 15 years or so. Sonographic guidance is not necessarily a requirement but, I feel, prevents the only potential side effect which would be atrophy of the skin and subcutaneous tissue which would occur if the needle is placed too superficially or if too much fluid is used which would lead to leakage of the excess fluid into surrounding tissues.
6) Why are these injections a better course of action than surgery, radiotherapy or cryotherapy? Can the injections be used after the previously mentioned procedures?
Cryotherapy and radiotherapy are non-specific therapies. Both are destroying tissue in a non-selective fashion. Collagenase and hyaluronidase, like all enzymes, have very specific functions and target tissues/reactions. The prime directive is to "do no harm."
7) Generally I find that only surgery is well known in the USA, why do you think this is?
I cannot answer that without stirring up a hornets nest. It is a political issue. The US system of medical politics has, for years, had a strong bias toward aggressive surgical approaches. I do a relatively high volume of surgery and certainly am not anti-surgery but there are times when non-surgical treatments are superior and need to be more objectively considered.
I thought that his response to question 6 was interesting, not because it is not true but because I think there is more to it than meets the eye, so I replied to him with a follow up statement to try and get more information from him:
One of your pros for Collagenase over radiotherapy and Cryotherapy is the specificity of treatment. I do not have a significant amount of knowledge for Cryo but I am sure it is also an ultrasound guided procedure to ensure that it is only the lump that it is hit with the treatment, although I think I appreciate that your point was more that Collagenase treatment is specific to the cause of the disease rather than Cryo which is not specific.
As for radiotherapy, you could argue, given that it is low dose treatment, that although all tissues will be hit with radiation that due to their proliferative state it will be the disease tissue that is targeted as these are the main replicative tissue and it is under replication that radiation is truly effective and through this means the radiotherapy is specifically targeting the disease.
While Collagenase is injected into the cells if it does get to other cells it could breakdown any collagen as the collagen in the diseased tissue is the same as that in the non-diseased tissue but is just more abundant.
I received the following response:
Addition on 28-03-2014:
The following information has been provided to me by a user from the International Dupuytren's Society forum who contacted Dr Davis after reading the above interview and is posted with permission from them and Dr Davis, the original responses can be found here.
1. Does the shrinkage of the fibromas decrease the progression of the disease? Or is it likely that you will continue to develop new nodules/fibromas?
The exact cause of plantar fibromatosis is not known so the effect of treatment on existing fibromas with respect to future nodules cannot be determined. Based on my experience, I have rarely had patients return with new nodules.
2. How many nodules can you treat at a time? Can you treat both feet at a time?
There is no limit to the number of nodules that can be treated at one time. Both feet can be treated at the same time. It would be normal to experience some discomfort once the numbness of each injection wears off so one need consider that.
3. I understand it may take more than one injection, why is that the case? And, typically how many injections are needed for each nodule? If multiple injections are necessary what is the time spacing between injections?
There is a limit to the volume of fluid that can be placed into a nodule. The nodules are largely composed of fibrous or scar tissue and have little expansion when injected so attempts to place too large a volume of fluid into a nodule would result in leakage of the fluid into surrounding tissues. Each injection provides about 30 to 40 percent shrinkage so one injection would not provide adequate treatment. We average two to three injections about 3 weeks apart.
4. Is there a difference in success rate of this treatment when treating early, and active Ledderhose?
I do not have sufficient information to answer that question. Most patients I have treated have fairly advanced nodule formation as treatment information about this is a bit sparse with the majority of medical advice favouring surgical treatment.
5. Are there any short term or long-term side effects to the treatment?
Short term: one to two days of tenderness. I am not aware of any long term adverse effects of treatment.
6. Is there "down time" to treatment where you need to be off your feet?
Down time is related to the number of lesions injected. It averages about 24 hours.
7. How much pain is associated with the actual treatment?
Pain varies from patient to patient but most patients find the treatment very tolerable. Depending on nodule location, we may inject them directly or perform a nerve block (posterior tibial block) which renders the sole of the foot numb before performing the injections.
8. How often do you see nodules that are treated come back or grow again?
I rarely see regrowth of nodules, probably less than 5%. A more common scenario may occur when there have been too few injections and nodules are not adequately shrunk, there is residual discomfort or pain.
9. I understand your success rate is close to 95%. Can you tell me roughly how many patients you have treated with Ledderhose?
About 105 to date.
10) It is my understanding that the H. injections that you do vary from the collagenase injections and therefore, perhaps, are more promising and successful?
Collagenase, in theory, should work as well as hyaluronidase. Unfortunately I have no experience with collagenase due to the expense of Xiaflex and because I have been happy with the hyaluronidase "technique" I use. One may consider the technique itself, which may not be consistent from provider to provider. I mix hyaluronidase with a small amount of a repository steroid, generally triamcinolone acetonide as well as a local anesthetic then use sonography to guide the injection into the center of the lesions. If the injection is too superficial then there is a risk of atrophy of the subcutaneous tissues, if too deep then, a potential loss of effectiveness. The goal of the injection is to create a zone of lesion atrophy in the center of the lesions such that the lesion collapses on itself. I have used sonography to aid the injections for about 9 years or so and feel that it does enhance the results.”
11) Have you through the years of treating patients formulated any of your own studies?
No. Would be interested in doing so. Currently, we could do case reports or possibly a retrospective study. Despite my personal experience the numbers of patients treated (by all the methods) is not large which makes statistical analysis problematic.
Statistics are sparse for all modalities. I am not aware of studies of any significance. The forums may be a means to attempt to gather statistics, perhaps in a retrospective study. Another issue to consider is that many of my patients travel from out of the area for the treatment so a portion of the results achieved is based on subjective information about results but not "before and after" measurement of the lesions. We encourage local patients to return to the office but, typically, when travelers from outside the area communicate relief or resolution of symptoms we do not ask them to return for an exam. A multi-centered research project would be optimal. Our treatment protocol tends to work the best on large lesions. We have seen two patients in the last year who had RT previously.
We know that hyaluronidase injections are relatively safe as hyaluronidase has a number of other uses; that is, experience with that enzyme is relatively large considering its range of applications. It is safer than RT although RT, when focused on a small area can be relatively safe. I believe that all should consider the maxim, "first do not harm." There is insufficient information with respect to long term efficacy of hyaluronidase but can only state that my "redo" rate is very small. I favor treatments that are as specific as possible. So in the case of a benign fibrous (scar tissue) growth, use of a agent highly targeted at that tissue such as collagenase or hyaluronidase seems best. Xiaflex is a relatively new brand name collagenase
indicated for Dupuytrens contracture. I called the manufacturer when it first came out. They had no plans to obtain an indication for plantar fibromatosis due to inadequate numbers of patients and were cautious to discuss that subject due to recent FDA penalties for the promotion of "off label" uses. It is costly to obtain an FDA indication for a drug. One legal means around that is to obtain "orphan drug" status.
Eddie Davis, DPM, FACFAS
He does not treat with collagenase. he treats with an injection of steroid to which he has added hyaluronidase NOT collagenase. The enzymes are totally different. Everybody injects dupuytrens nodules with steroid if they are really painful.
REPLY BY DR DAVIS:
That is correct, the enzyme is hyaluronidase. We use the Vitrase brand of hyaluronidase. Xiaflex is a brand of collagenase. They are different enzymes but with similar effects on scar tissue so the comment about "totally different" is a bit misleading. Also misleading is the comment "he treats with an injection of a steroid which he has added hyaluronidase" as that appear to be an attempt to to de-emphasize the role of hyaluronidase. Perhaps a more accurate statement would be "he treats with hyaluronidade to which he has a added a steroid, triamcinolone acetonide, and a local anesthetic."
A quick addendum: enzymes are entities that react with specific tissues in the body. For example, collagenase breaks down bonds in collagen and hyauronidase breaks down hyaluronic acid. Connective tissue in our bodies have a number of components and each enzyme will target a specific component due to its specificity. What matters is the end effect or therapeutic effect that will be achieved. We can look at a painful overgrowth of connective tissue and reduce by "attacking" different components of that tissue.