DART – Frequently Asked Questions

This page contains a collection of frequently asked questions. We hope that you will find them useful.

We appreciate the research and efforts of DART admin Martin Sharman which led to his creation of this helpful FAQ for DART members.  Last updated about 2017

FAQ INDEX

1.    What are early symptoms of Dupuytren's disease?
2.    What are the symptoms of Ledderhose disease?
3.    What are the symptoms of Peyronie's disease?
4.    What happens as Dupuytren’s disease progresses?
5.    How do I know if the disease is progressing? 
6.    What happens as Ledderhose disease progresses?
7.    What happens as Peyronie's disease progresses?
8.    How fast does Dupuytren’s disease progress?
9.    How fast does Ledderhose disease progress?
10.  How fast does Peyronie's disease progress?
11.  What places does Dupuytren’s show up?
12.  What places does Ledderhose show up?
13.  What places does Peyronie’s show up?
14.  Are DD, LD and Peyronie’s disease the same disease?
15.  In simple terms, what is happening to my hand?
16.  Are Dupuytren's and Ledderhose disease curable?
17.  What is Dupuytren's diathesis?
18.  Why does the disease recur?
19.  Can someone of any age get Dupuytren's or Ledderhose disease?
20.  How can I tell if the disease is active?
21.  What happens if I elect to do nothing?
22.  Can testing determine if I have Dupuytren's disease or Ledderhose disease?
23.  How can I monitor the progress of the disease before contracture sets in?
24.  What should I consider before seeking RT?
25.  Are women more likely than men to get either Dupuytren's or Ledderhose disease?
26.  I have Dupuytren's disease (or LD). Am I likely to get Ledderhose disease (or DD)?
27.  What are risk factors for developing DD or LD following injury?
28.  Is it possible that my Dupuytren's disease started because I broke my wrist a few years ago?
29.  Since my LD started with an injury, can I get it in my other foot or hands if they get injured?
30.  What do we know about occupational risk (e.g. vibrating tools)?
31.  Why do some people call DD "the Viking disease"?
32.  What are the technical names for the parts of the hand and feet?
33.  What is known about the genetics?
34.  How can it be genetic if no one in my family has it?
35.  I have Dupuytren's disease. How do I know whether I have a high diathesis?
36.  Is the disease caused by trauma, or is it genetic?
37.  What are the benefits of genetic testing? Can I forewarn family members?
38.  Are there any foods that might make the disease worse?
39.  Does having Dupuytren's disease affect your risk of developing other conditions?
40.  What are some related fibromatoses?
41.  Before RT, what if I have other underlying issues?
42.  Why are the diseases more common in people with diabetes?
43.  How does RT work to stop DD and LD?
44.  Does RT work for everyone?
45.  Can I expect any remission (improved function, reduction in nodules) as a consequence of RT?
46.  What percentage of people with DD will progress to contracture?
47.  Can RT cause cancer?
48.  Is RT painful?
49.  Is RT effective at all stages of the disease?
50.  How is this treatment different than radiation given to a cancer patient?
51.  What are doctors’ thoughts on re-radiating the same area?
52.  Am I likely to have any side-effects from radiation therapy?
53.  What might happen to the skin where I'm radiated?
54.  Not sure what this question is?
55.  Can I have RT with a steel pin in my wrist?

1.  What are the early symptoms of Dupuytren's disease? 

The very first thing to be said about Dupuytren's disease is that it is different in every person, to the extent that some researchers doubt that it is even a single disease. Descriptions of the disease are invariably peppered with words like “often”, “mostly” and “usually”; your symptoms may be puzzlingly different from any single description. Although no two hands with Dupuytren's disease look alike, most doctors in Europe or North America (where the disease is surprisingly common) will recognise it without difficulty.                      FAQ – courtesy of DART Facebook Group

The next thing to say about early symptoms is that almost everybody misses them. It has been shown again and again that most people who have Dupuytren's disease don’t realise that they have it. Most people have noticed nothing wrong, or if they have noticed changes in their hands, they have put them down to calluses or a natural and unremarkable consequence of getting older.

The first thing most people notice – if they notice anything – is one or more firm areas in the palm of a hand, little lumps under the skin, usually next to the crease in the palm closest to the fingers (and often in line with the third, or ring finger), which are usually completely painless though perhaps slightly tender to pressure. These firm areas gradually become harder, developing into nodules whose resilience gradually passes from that of a tomato to that of an orange, a tennis ball and finally, a coconut.

Dupuytren's disease is not always painless. Unfortunately, many doctors use “painless” as a diagnostic characteristic of the disease – which often leads to misdiagnosis when people present with painful hands.

Nor does the disease inevitably start with firm areas. You might instead notice dimpling in the palm or in the side of the phalange of a finger. These pits in the skin are often more or less V-shaped, as if something under the skin were pulling the skin to one side (which is exactly what is happening). You may find that the nodules become more distinct and easier to feel as the fat underlying the skin becomes thinner as the disease progresses. Pitting, dimpling and (often) V-shaped hollows of the skin may develop and increase near the nodules.

A fairly good diagnostic characteristic of Dupuytren's disease is that the mass of the nodule is fixed to skin (it won’t slide about under the skin) and deeper fascia (you can’t really move the nodule relative to the palm, though there may be some movement relative to the underlying tendons and bone).

Usually the disease starts – and may remain – in one hand, but almost half of those with Dupuytren's disease have it in both hands. Bilateral it may be, but it almost certainly won’t be symmetrical.

Some people feel tingling and itching in the palms and fingers and may liken it to the feeling you get as your hands warm up after making snowballs with bare hands. This sensation, which can be maddening, seems to be an indication of active disease.

For some people, the disease is very painful and can make it nearly impossible to use the affected hand.

One final thing about early symptoms is the psychological reaction one may have to the discovery of Dupuytren's disease. While some people are alarmed and quickly seek professional advice, many – perhaps most – react with indifference or by avoiding thinking about the nature of what is developing in their palm. And for most people, this denial of reality has no practical consequences since the disease does not develop much in most affected hands.

2.  What are the symptoms of Ledderhose disease?

Where Dupuytren's disease affects the palm of the hand, Ledderhose disease affects the sole of the foot. The two are so closely linked that a famous hand surgeon named Hueston stated that, “The first clinical examination of every patient with Dupuytren's disease must involve removal of the patient's shoes.” (Hueston, J. (1990). Dupuytren’s diathesis. In: Dupuytren’s Disease Biology and Treatment. R.M. McFarlane, D. McGrouther, and M.H. Flint, eds. (Churchill Livingstone), pp. 246–252.)

Most people with Ledderhose disease don’t know that they have it – at least at first.

Normally, the first inkling of the disease is distention or swelling in the sole of the foot that is painful when it pressed against a shoe or the ground. The pain may be severe enough to discourage you from walking – and later, make walking impossible.

For this combination of reasons – absence of pain at first, then rather sudden pain as the swelling reaches a size large enough to touch the shoe or the floor – many people get the impression that the disease has popped full-grown from nowhere.                FAQ – courtesy of DART Facebook Group

The swelling, which gradually becomes a lump, typically appears in the middle of the sole, often in the arch of the foot, but also in the toes and sometimes in the heel or side of the foot.

The lumps are usually slow-growing and generally less distinct and less easily palpated than those of Dupuytren's disease. Pitting is not seen, and, unlike in Dupuytren's disease, the overlying skin is freely movable.

Ledderhose disease, which affects about 1 in 5 older people of European descent, is less common than Dupuytren's disease. People with Dupuytren’s disease are quite likely to have Ledderhose disease.

Ledderhose disease resembles Dupuytren's disease in that it is different in every person with the disease but is unlike it in that it is less frequently (though unfortunately still rather often) bilateral.

3.  What are the symptoms of Peyronie's disease? FAQ – courtesy of DART Facebook Group

Peyronie’s disease manifests as flat lumps, plaques or hard bands in the lining of the erectile tissue under the skin of the penis. These plaques may cause the penis to bend, develop a narrow neck along the shaft, or to contract. The plaque usually manifests as a hard lump where the penis curves. The disease may cause the penis to hurt with or without an erection, and for men with severe cases, an erection may become rare or impossible.

It is not known how common Peyronie's disease is, partly because men with the disease are often reluctant to go to a doctor, but it probably, and rather astonishingly, affects something like 2% - 10% of men of European ancestry who are between 45 and 60.

Unlike Dupuytren's and Ledderhose disease, Peyronie's disease seems to have no particular tendency to be associated with men whose ancestors came from northern Europe.

4.  What happens as Dupuytren's disease progresses?

In most cases, the disease does not progress beyond nodules and pitting. 

Sometimes, the disease starts to create linear structures under the skin called cords, which typically (but not always) run up the palm from the nodules into the fingers. 

The disease then sometimes causes these cords to contract, often forming increasingly sharp ridges in the palm and lower joints of the fingers, and sometimes, as the disease develops further, dragging in the first phalanges of the associated finger (technically, the (MCP) metacarpophalangeal joint and the (PIP) proximal interphalangeal joint) and forcing the finger into the characteristic irreversible flexion contracture of the disease. 

Many people only go to the doctor about the disease when their finger starts to contract in this way. For many people, in fact, the contracture is the first symptom that they notice.

5.  How do I know if the disease is progressing?

The disease can, and very often does, progress silently. Most people with the disease don’t know that they have it. Some don’t know because the nodules are mistaken for callouses or random sore lumps in the sole. Some don’t know they have it even when it has progressed so far that one or more fingers are curling toward the palm. They imagine that it is just a standard consequence of getting older. 

Painlessness used to be (and still is for some doctors) a diagnostic for the disease. So although some people feel itching or tingling, and some people find it painful, many – perhaps most – people with the disease don’t experience the tingling or pain that is so characteristic for others. So tingling or pain are symptoms of the disease for some people, but absence of tingling, or painlessness, is not a sign that the disease isn’t progressing.

If you see changes in your hands or feet over the course of a couple of months, then the disease is active, even if it doesn’t call attention to itself. And perhaps if you see structural changes in that kind of time frame it will progress just as much in the next couple of months, which is to say rather rapidly. Or perhaps it won’t. This disease is very much stop-start, but one in which we have no forewarning of how long the pauses will be, or how rapid the spurts. 

In all the very limited medical literature on the subject, it seems that radiation therapy is most likely to be effective when it happens earlier, and the earlier it is applied, the more likely it is to be effective. Anyone with early-stage Dupuytren’s or Ledderhose has a very difficult decision. Let me illustrate it with a famous scene from a 1970 film, Dirty Harry. Harry, a policeman, is talking to a thug who is prone but reaching slowly for his gun. Harry says,

‘"Did he fire six shots or only five?"', says Harry. 'Well to tell you the truth in all this excitement I kinda lost track myself. But being this is a .44 Magnum, the most powerful handgun in the world and would blow your head clean off, you've gotta ask yourself one question: "Do I feel lucky?" Well, do ya, punk?’

In the case of this disease, waiting another month is like betting that Harry has no rounds left. But the disease is unpredictable and might just stop right now – Harry has fired all his bullets. Radiation therapy might be unnecessary. You cannot know the future. So all you can do is balance risks. 

But here’s the thing. Any progress the disease makes, however small, is likely to be irreversible. It might stop, or it might go on. It won’t go back. So, the risk is about balancing “it’s finished progressing and therapy would be a waste” with “next time I look, things will be a little worse, and therapy might prevent that”. 

Now all this means that we have to balance “act now and accept the bad things about radiation therapy” with “wait and hope things won’t get worse”. This decision is made a little more difficult by the knowledge that for most people with the disease, things don’t get worse. But you are not most people. 

If you know the disease is getting worse – you’ve seen structural changes over the last few months, for example – the little knowledge you have tells you that you are possibly not among the majority for whom the disease never progresses far. The hope that things won’t get worse begins to look more like optimism, and the between hope and optimism there is a yawning gulf.

So that means that the decision looks like a non-decision, except for the “bad things about radiation therapy”. Which are that it (a) doesn’t always help, (b) is inconvenient and costs a great deal of money, (c) sometimes has side effects. 

There’s nothing anyone can do about (a). Some people seem to get little or no benefit from the therapy, and we don’t know why. It seems to be a small minority, though because the failure is such a huge blow, we tend to hear about each case where new nodules and cords form after RT, so the possibility of failure cannot be far from our minds. 

So (b), then. Yes, it’s inconvenient, but so is being crippled. It costs a lot. It may cost too much, in which case it isn’t an option. It may cost enough that you have to relinquish the opportunity to do something you really wanted to do but set against that is the possibility of losing the function of your hand or being unable to walk or going for equally expensive (and far more painful) surgery later. 
Which leaves (c), the side effects, which tend to be trivial (red skin, dry skin, thin skin, peeling) or at least temporary (sunburn, blistering). Set against the possibility of stopping the disease, even for a few years, these seem more like inconveniences than obstacles.

6.  What happens as Ledderhose disease progresses?

In most cases the disease never bothers the person, persisting as rather indistinct lumps that may or may not be tender. 

Sometimes previously painless lumps become tender and may make walking and standing painful, in some unfortunate people to the point that they cannot stand or walk. 

Only rarely does the disease cause cords to form or the toes to contract.

7.  What happens as Peyronie's disease progresses?

In about 2 in 3 men, the disease stabilises and does not progress, while the pain associated with erections decreases. In the remainder, the curvature associated with Peyronie's disease gradually worsens.

                                        FAQ – courtesy of DART Facebook Group

8.  How fast does Dupuytren’s disease progress from the first firm areas to full contracture of a finger?

From an actuarial perspective, most people with Dupuytren's disease die before it develops beyond nodules or cords. 

Putting this less dramatically, the chances are that someone who has discovered nodules in their palm will never have to deal with crippled hands.

The activity of the disease varies from person to person, and, for those with bilateral Dupuytren's disease, between hands. 

It sometimes progresses steadily but in most cases it progresses by fits and starts. Sometimes the nodules and cords may even soften and diminish, and in rare cases, the disease has spontaneously disappeared.

Most severely deformed hands have taken several years to develop, but cases are known in which a finger has contracted a few weeks after the lumps in the palm were first noticed.

In a large enough population, somewhere between 2% and 7% of people with nodules in their palms will develop cords before the end of the year. A similar percentage who start the year with cords will develop 10 or more degrees of contracture.

9.  How fast does Ledderhose disease progress?

Its progress is impossible to predict, often remaining static but sometimes, without warning, developing quickly.

10.  How fast does Peyronie's disease progress?

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11.  Can I get Dupuytren's disease in places other than the palm, and palm side of the fingers?

Dupuytren’s disease is almost always confined to the palm and fingers, but can sometimes occur in the wrist or, rarely, in the forearm. Quite commonly, a form of Dupuytren's disease called Garrod pads, or knuckle pads, develops on the outside (the back) of the knuckle joints (technically, the dorsum of the proximal interphalangeal joints). These lumpy pads can sometimes be painful.

Nodules like those of Dupuytren's disease have been reported elsewhere in the body. These nodules, called nodular fasciitis, appear in the superficial fascia - usually in the upper torso and upper arms - and typically affect people in their 20s and 30s. They sometimes appear very quickly - in a matter of weeks - and normally disappear again.

A few people with Dupuytren's disease develop fibromatosis on the back of the hand.

12.  Can I get Ledderhose disease in places other than the sole of the foot and the underside of the toes?

Most cases of Ledderhose disease manifest as lumps near the inner edge of the sole, at the highest point of the arch. In rare cases, however, Ledderhose disease has been reported in the side of the foot and ankle.

13.  Can I get Peyronie's disease in places other than the penis?

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14.  Are Dupuytren's, Ledderhose and Peyronie’s disease the same disease, simply affecting different places?

These three conditions, together with Garrod’s pads, are similar from a biochemical, histological and pathogenic point of view. They are also tightly related, so that having one of them greatly increases the probability that you will also find yourself with another. The family of genes that predisposes you to one seems to predispose you to another. 

They are not, however, histologically identical, their manifestations are different, and they do not progress in the same way. This variance may result from the different ways in which the collagen and other tissue is organised in the palm, sole and penis, the histology and development being channelled differently by their contexts, but it is possible that elements of the disease are sufficiently different from one context to another for them to be regarded as different diseases. 

It is even possible that each one of them is not really a single disease, but a closely-related set of diseases that manifest in very similar ways. 

Although about 1 in 5 men with Peyronie's disease also have Dupuytren's disease, it seems to be rather different from both Dupuytren's and Ledderhose disease in that it affects men without regard to their ancestry (there's no tendency for their ancestors to come from Europe), it can appear very abruptly, and there is some evidence that it can also sometimes disappear without treatment. Furthermore, it seems to respond to sonic shock, which has not proven to work particularly well with the other diseases.

Of particular significance to DART, the diseases do not seem to respond in the same way to radiation therapy, with Peyronie’s perhaps being the most responsive and Dupuytren’s disease the most recalcitrant.

Despite these differences, the diseases are sufficiently similar for them to be discussed as if they were a single disease (superficial fibromatosis) with different manifestations in different parts of the body. This is the approach taken in these FAQs, except where the diseases are sufficiently different to be treated separately.

Although Dupuytren’s and Ledderhose present differently (diffuse nodules and no cords, randomly oriented fibres rather than aligned ones, etc) the default position is that they are manifestations of the same underlying pathology in different environments. This assumption (and it is a big one) leads to the conclusion that what works for Dupuytren's should work for Ledderhose. Is that true? Murphy's Law says "Probably not", but it's the best starting point that we have.

15.  In simple terms, what the heck is happening to my hand?

In simple terms, the normal process of wound healing and associated scarring is running a little hot. Cells whose job it is to create, maintain and dissolve collagen, the strong elastic tissue that gives muscle and tendons their form, are doing their job a little too well, reproducing themselves a little too enthusiastically and not dying off when they are supposed to.

In slightly greater detail, something in your genes is instructing your body to set up conditions similar to those that prevail when you have wounded yourself. In these conditions the cells called fibroblasts that create and destroy collagen, multiply and at the same time produce more collagen than they destroy. 

The fibroblasts are found mainly in the fascia of the palm and sole, a tough sheet of collagen-rich tissue that helps give the palm of the hand and sole of the foot the mechanical structure and strength that these areas need. This excess collagen heaps up as nodules. 

Tiny fibres run between the nodules and the skin above them, binding skin to nodule. 
At some point the fibroblasts begin to generate long protein molecules that have the capacity to contract. These modified fibroblasts called myofibroblasts, begin to shorten the collagen by an ingenious ratchet mechanism. 

This continuous shortening rucks up the skin above the nodules and cords, while gradually tightening the cords. The ever-tighter cords reel in the finger joints, with the result that the finger begins to curl in the characteristic contracture.

In much greater detail, histology and biochemistry of the disease turns out to be extremely complex. Less is known about genetics, but genetics, too, seems not to be simple.

16.  Are Dupuytren's and Ledderhose disease curable?

No. At least, not yet; and given the complexity of the disease, it seems unlikely that a silver bullet awaits discovery.

17.  What is Dupuytren's diathesis?

The word “diathesis” is used in medicine (or was - it's rarely heard these days) to mean a predisposition to a disease or an allergy. Normally the predisposition is understood to be hereditary but it may also be constitutional.

By way of anecdote, illustration, and example, the following passage is taken from one of the earliest documents that link “diathesis” and “Dupuytren”. 

In 1878, Dr. William Adams wrote,
“With regard to the cause of this affection, most authorities agree in assigning it, in the great majority of cases, to a local cause, and believe it to be produced by pressure from the use of tools in various occupations; and it is said that carpenters, gardeners, and gunners, are especially liable to it. 
Sir James Paget refers to the elder men occupied in wire-drawing and lock and key-making, as being subject to this condition. 

It is also generally admitted that this form of contraction may take place from constitutional causes, independently of any local cause, and that it is then traceable to a gouty diathesis.

Sir James Paget points out the dependence of this contraction in some cases upon the gouty diathesis and believes that the adhesion of the palmar fascia to the adjacent sheaths of tendons and the integuments forms a point of diagnosis. 

My own opinion is that it nearly always depends upon a constitutional rather than on any local cause, and essentially, I regard it as depending upon a gouty diathesis. In favour of this opinion, I would refer, first, to the class of patients in whom it occurs. 

During a connection of more than twenty years with the Royal Orthopaedic Hospital, I have seen but very few cases of Dupuytren's contracture in the labouring class; and the cases that did present themselves generally occurred in butlers and in-door servants. 

It seems, however, to be an affection of common occurrence in the middle and upper classes of society. The cases which have fallen under my observation have occurred in clergymen, barristers, medical men, officers of the army and navy, and merchants; the only condition common to the whole series being a disposition to gout. 

Coexisting with the finger-contraction, in the cases which I have seen there have been generally other manifestations of a gouty tendency, more especially to that form we recognise as rheumatic gout affecting several articulations and often causing enlargement of the joints of the fingers rather than true inflammatory gout, affecting the great toe. 

Secondly, I would refer to the frequent occurrence of this affection in the left hand only, and to its occurrence in both hands, which we can hardly explain by any local cause. 

Thirdly, I would refer to the fact that in several instances I have known two brothers suffer from it; and in some cases, the father and son have been similarly affected; so that, for these reasons, I am disposed to attach far greater importance to the constitutional than to any local cause.”
(Adams, W. (1878). Contraction of the Fingers (Dupuytren’s Contracture), and its successful Treatment by Subcutaneous Divisions of the Palma Fascia, and Immediate Extension. British Medical Journal 1, 928.)

In 1990, a famous and respected Australian hand surgeon named John Hueston reintroduced the concept of Dupuytren's diathesis. He remarked, 
“Derived from the Greek root to dispose or distribute, the word diathesis can be seen to give a guide to the disposition of what the Oxford English Dictionary terms 'a permanent condition of the body which renders it liable to a special disease'. This permanence has been demonstrated to depend on an inherited genetic pattern or 'disposition' of the chromosomal material responsible for the development of Dupuytren's disease. Therefore, it should be clear that it is impossible for a patient with Dupuytren's disease to have no diathesis.”

He goes on to state that stronger diathesis is indicated if the person with the disease is young, also has Ledderhose disease or Garrod’s pads, and the disease has exhibited a rapid onset and progress. 
Stronger diathesis is also likely if the person has “several close blood relations with Dupuytren's disease”, but he points out that “the absence of a family history should not lead [one] into presuming a low” diathesis, because many people never realise they have the disease. 
He remarks that, “attempts to grade numerically the degree of diathesis have not yet appeared in the literature but should [in any case] be regarded with a healthy scepticism in this essentially clinical process of individual assessment.”
Hueston, J. (1990). Dupuytren’s diathesis. In Dupuytren’s Disease Biology and Treatment, R.M. McFarlane, D. McGrouther, and M.H. Flint, eds. (Churchill Livingstone), pp. 246–252.

Two years later, in 1992, John Hueston clarified the concept by explaining,
“Diathesis is just an old-fashioned term for the variable penetration of an autosomal dominant.” 
In less technical English, he is saying that diathesis is a genetically-determined characteristic that you can inherit from either parent - “autosomal” means that the genes are not carried by the X or Y chromosomes. Having inherited it, you may not necessarily exhibit the characteristic. 

Hueston continues,
“The diathesis is present in every member of a Dupuytren family. If the diathesis is very low, there will be no clinical manifestation of Dupuytren's Disease, but it may appear after an injury, either to the hand or to that upper limb, such as a fracture or elbow dislocation or even a mastectomy.
If the diathesis is mild it will be manifest as a mild disease with no indication for surgery.
If the diathesis is less mild, disease requiring surgery will appear but no recurrence will follow.
If the diathesis is stronger there will be recurrence in the operated field, but probably not extensive enough to require secondary surgery.
If the diathesis is very strong, as is often the case in young patients, we can expect early recurrence and the need for radical surgical intervention.
A clinical assessment of the strength of this diathesis should be attempted, but is by no means infallible.”
Hueston, J. (1992). Lessons in Dupuytren’s Disease. Ann Hand Surg. 11, 349–354.

The word is very frequently misused in more recent writings on Dupuytren's disease, so that “diathesis” is used as if it were synonymous with “strong diathesis”. 

We can read, for example, “Patients with these associated findings are considered to have a Dupuytren diathesis and are prone to progressive and recurrent disease.”

In other papers we can find direct misquotes of Hueston, as for example, in:
"Some clinical characteristics of patients with DD are related to a more aggressive course of the disease or diathesis. In 1963, Hueston postulated the idea of a DD diathesis and described 4 factors defining this subset of disease: early onset of disease, bilateral involvement, positive family history, and the presence of ectopic lesions (knuckle pads, Ledderhose disease, and Peyronie’s disease).
In 2006, male sex as a diathesis factor was added, “early onset of disease” was refined to age of onset younger than 50 years, and the ectopic lesions were restricted to the presence of knuckle pads only."

What factors do I look at to place myself on the diathesis graph?

          Unfortunately, at the moment we haven't got the objective information to make the graph anything but conceptual.
 
On the genetic axis of the diagram we don't yet even know what genes are involved, which alleles of those genes make a difference, or what difference they make. We know that ggenes are involved, and that there are quite a large number of them, that they are located on different chromosomes and more or less where those locations are within the chromosome. If I can make a very loose analogy, we know that the taste of the meal we're cooking is influenced by the contents of jars from the spice rack, but we don't yet know which spice does what, or even how many jars are involved in any given attempt at making the dish. And to push that analogy a bit further, we also know that the dish is influenced by which shelf in the supermarket we get stuff from, but we can't yet read any of the labels on any of the cans or boxes.

On the other axis, we know that people who exhibit the disease early in life very often (but not always) develop the disease faster and suffer more pronounced symptoms than people who develop it later. There's some evidence that women tend to develop it faster than men, but it's not terribly solid evidence yet. So, all we can say at the moment about that axis is that if you're diagnosed with the disease as a 20-year old, and particularly if you're a woman, you belong to a population that in general has a high diathesis. But your mileage may vary. Everyone is different, and it's only when large numbers of people are seen as a group that some patterns vaguely appear.

All this is very frustrating and can be pretty frightening, but that's where we are with our understanding. And unfortunately, the data are extremely scattered. It's very unusual for anyone to collect enough data on enough people for long enough to begin to pick the story apart. Most of us aren't so interested in taking part in clinical trials - particularly as members of control groups - and most doctors and surgeons aren't all that interested in organising and finding funding for the research. There are many other diseases with higher priority for one reason or another.

18.  Why does the disease recur?

It’s not so much that it recurs as that it never goes away. The genes that set you up for Dupuytren's and Ledderhose disease don’t go away, and the abnormal biochemistry never changes. So, after any intervention – particularly a surgical one – all you have done is alleviate a symptom for a while, but if the disease was active before the intervention it has no reason to calm down after the intervention. 
This is different in the case of radiation treatment, since the radiation destroys some of the tissue that is creating the abnormal biochemistry in the first place, and therefore (when it works as intended) tends to block the progress of the disease – at least until it has had time to rebuild the destroyed cells.

Some people get RT and never see any recurrence, while others - the very unfortunate ones - find the disease just surges on despite the RT. 

Oncologists may be readier to treat nodules and cords that appear outside the irradiated area than they are to treat nodules that become active within the area - so called "in-field failure". The doctor would take many things into account in their decision, in particular the way in which the person responded to the earlier treatment, and how much total radiation the person had already absorbed.

19.  Can someone of any age get Dupuytren's or Ledderhose disease?

Both diseases are considered to be diseases of middle and old age because the onset is typically seen in people in their fifth or sixth decade. But people of any age can get it, and there are even recorded cases of particularly unfortunate people being born with the disease. Younger people are less likely to develop the symptoms, but unfortunately, when younger people do develop the disease, the disease is likely to be more aggressive and to progress faster. Such people are said to have a strong diathesis for the disease.

20.  How can I tell if the disease is active?

The key element is change – change in the appearance and feel of the diseased area over the last few months. Activity in Dupuytren's disease means that nodules are growing and hardening, dimples may be appearing and deepening and cords may be emerging, lengthening or tightening. In Ledderhose disease the lumps may be becoming more distinct or more painful. Particularly with Dupuytren's disease, you may also feel a tingling or tickling that seems to indicate active disease, sometimes together with a hot feeling in the palms. In some people, the palms may also feel unusually damp.

21.  If I just leave it and do nothing, what is likely to happen?

For most people, nothing much; for a few, more or less rapid progress in the disease. 

A major study in Iceland showed that most people who started the year with nodules and cords had no changes by the end of the year, but 2% of such people had developed contractures, and 2% of those with contractures at the start of any given year had worsened by the end of the year. 

The study doesn’t show this, but it seems likely that those of us with a strong diathesis are “fast track” people who will see the disease progress rapidly, while those with a low diathesis will see little change year on year. 

If you have low diathesis, then depending on how old you are, the chances are good that your Dupuytren's or Ledderhose disease will remain more or less as it is until you die. 

Of course, the younger you are, the more likely it is, from a statistical point of view, that your disease will progress because it has more years in which to do so; unfortunately, if you were particularly young when the disease first appeared, it’s possible that you have a strong diathesis.

22.  Are there any blood tests or biopsies that can determine that I have Dupuytren's disease or Ledderhose disease?

No. The diseases are very close to what the body does normally, so there are no known indices that can be discovered in either blood or biopsy.

23.  Is there any way to monitor the progress of the disease before contracture sets in?

Taking photos of the affected hand or foot at regular intervals may provide a valuable record. DART provides guidance on taking photos, but for you to use them to monitor the progress of the disease, you will need to take care to take each photo under similar lighting conditions (direction, colour and intensity) with the same background, camera, focal length and camera-to-hand distance. You will also need to repeat the placement of your hand and fingers from photo to photo.

For Dupuytren's disease, it is worthwhile to record the flexibility of your fingers. Again, the method is described in detail in DART, but consists in placing the hand palm down on a table and recording how far you can raise the fingertip of each finger above the table while holding the palm-finger joint down on the tabletop.

If you have Dupuytren's disease then mapping the span of your fingers is a third way of recording progress. Spread each hand as wide as possible while palm-down on a piece of paper and trace the outline of the palm, fingers and thumb.

24.  What elements should I consider when deciding whether to seek RT?

Most people with either Dupuytren’s or Ledderhose disease find that it never progresses to the point that it significantly reduces the quality of their life. Thus, they never need any treatment. 

This is the one thing that makes the decision most difficult: do I bet that in my case the disease will not progress, or do I decide to take action and get radiotherapy that I might well not have needed? Because if I’m going to take action it might be best to move quickly…

The probability of a good outcome is increased if the disease is in its early stages – it’s statistically most effective when the irradiated hand has only tiny nodules or shows nodules and no cords, or cords that are only starting to appear. 

A similar remark holds for Ledderhose disease although some anecdotal evidence suggests that the radiation may more effective later into the disease than with Dupuytren's disease.
 
With Dupuytren's disease, once contracture sets in, the efficacy of radiation drops. Many radiation oncologists who treat Dupuytren's disease are reluctant to irradiate hands in which the finger is curled in towards the palm by more than about 10° because they know it won’t do much good.

Other considerations include your health history – have you been treated for something else using radiation, have you got other morbidities in the hand or foot that you are thinking of treating, do you happen to be more or less sensitive to radiation than most, and so on. 

A FAQ can’t answer most of these questions – you’d need to talk to a doctor or a radiation oncologist about your case. 

One health-related question that a FAQ can at least address is radiation therapy after a surgical intervention. Because the surgery does not do anything to stop the recurrence of proliferating fibroblasts – and hence, depressingly frequently, the rather rapid reappearance of cords and contractures – it may be beneficial to treat the operated area with radiation to kill off the proliferating cells. Whether this is true in your case, however, will be something for you to discuss with your radiation oncologist.

A FAQ can’t answer one of the most important questions of all - if it were to progress, how much would the disease interfere with your capacity to earn your living, with your hobbies and your life in general?

The high cost of the treatment may make it unrealistic for you to consider radiation therapy. This will often come down to how good your insurance cover is. There are many discussions in DART on this issue.

25.  Are women more likely than men to get either Dupuytren's or Ledderhose disease?

No. All the evidence points to an earlier onset in men, who tend to get the disease about a decade earlier than women. The older the cohort, however, the more the proportion of men and women becomes equal, until with very old people about as many women as men have palmar or plantar fibromatosis.

You may be interested by the clear progress of understanding demonstrated by the following list of quotations about Dupuytren's disease. Each of them is taken from the medical literature.

- I have seen no true case in a female. - Mr. Keen 1877
- I have never seen it in women. - William Adams 1878
- This condition is never met with in women. - Dr. Myrtle 1881
- This curious affection is doubtless of very rare occurrence in the female sex but is not altogether unknown. I have at the present time an unmarried lady under my care who is in her eighty-ninth year, the fingers of whose right hand began contracting about two years ago. I am, moreover, informed that one of this lady's sisters, who died at the age of seventy, suffered from a similar contraction of the fingers of the right hand. - T.A. Carter 1881
- This affection very rarely occurs in women. - William Adams 1882
- Among 440 women were found 15 cases of indurated, thickened, and contracted fascia alone, and also 11 cases of well-marked Dupuytren's contracture of the fingers. - Mr. Noble Smith 1884
- [I have] seen six and operated on four [cases in women]. But I still considered it roughly true that the disease is ten times as common among men as among women. - Mr. Keen 1884

1900-1950s
- The disease occurs in men much more frequently than in women. I found 57 cases of Dupuytren's contracture among 270 old men, or 21%, and only 3 cases among 168 old women, or 1.8%. Dr. Noble Smith found 55 cases of the disease among 300 men, that is 18.3%, and 15 cases among 400 women, that is 3.75%. - Kenneth Black 1915
- Sprogis (1926) traced Dupuytren's contracture through three generations of a certain family, and found 17 cases among 53 persons, only 2 of which occurred in women. - Davis and Finesilver 1932
- The condition occurs mainly in men, only 15% of the patients being women. - Anon 1949
- This series of 22 cases of Dupuytren's contracture included 12 men and 10 women. A trend but no conclusive evidence may be noted from this small series of cases. The trend indicates that sex in itself has very little bearing on the etiology of this condition. - Charles LeRoy Steinberg 1951
- The low incidence in women deserves further study. Most cases in women occur after the menopause. A study of this disease and its relation to ovarian function would be important. - Joseph Boyes 1954
- Dupuytren’s contracture has often been thought to be a disease predominantly of men, as evidenced by surveys of previous series which gives a total ratio of 7:1. Our total series consisted of 43% female and 57% male patients. Of the entire group of 175 patients with Dupuytren’s contracture, fifty-one were females, thus giving a ratio of 3:1. - Yost, Winters and Fett 1955

1960-1990s
- The known facts, however, are quite clear-cut. It is a disease predominantly of men, although a few women do get it. - A.R. Wakefield 1960
- No significant sex difference is present in the incidence of Dupuytren's contracture in subjects over 40 years. In the group aged 39 years and under, a 5.05% incidence was found in 594 males, and a 2.55% incidence in 157 females. Dupuytren’s contracture occurs in women almost as frequently as in men. Previous estimates of an incidence in females of 10% to 20% of that in males (Kanavel Koeh and Mason, 1929), have been based on figures derived from operation statistics which do not give a true indication of the incidence in the general population. - John Hueston 1960
- Dupuytren’s contracture affects men seven times more often than women, but it is not rare in women. In women the results of surgery may be most disappointing; post-operative function is very variable and the tragedy of the " frozen" hand sometimes occurs. Poor results are apparently seen more often in women than in men, but no analysis has, to the writer's knowledge, been published. - Antony Wallace 1964
- It is seen more often in men than in women, especially in the younger age groups. - Su and Patek

1970-1980s
- It is a disease of dominant inheritance expressed more commonly and earlier in men than in women. - Honner, Lamb and James 1971
- The disease was detected in 9.4% of the 6888 men and 2.8% of the 9062 women. The prevalence among men rose from 0.2% in the 20-24-year class to a maximum of 36.8% at 70-74 years, and then declined. For the women the prevalence rose from 0.3% for the 40-44-year class to a maximum of 25% at 80-84 years, after which it diminished. The ratio of men to women was infinite in the youngest classes but fell almost hyperbolically to 1.2 in the oldest group. - Otto A. Mikkelsen 1972
- It is more common in men than women. - Fisk 1974
- A man of 45 has a 59% chance of having Dupuytren's already if he is destined to develop it, a woman of the same age, only 17%. - J.I.P. James 1974 
- At corresponding ages, the contracture is more severe in men than in women, and more severe in the right than in the left hand. - Mikkelsen 1976
- While the assertion of some 19th-century authors that the condition does not occur in women is clearly wrong, there is certainly no doubt that it is far more common in males than females. - Phillip Matthews 1979
- Of the 919 patients examined, twenty-one men (5%) and fifteen women (3.5%) showed evidence of Dupuytren's contracture. The average age of the affected men was 59 years (29-75 years) and of the women 63 years (39-81) years). - R. P. Mackenney 1983
- Women are afflicted only half as frequently as men when the incidence in a general population is studied. When, however, operation statistics have been used to compare sex incidence, women are found to constitute only one in eight or one in ten of those undergoing surgery. This lower incidence of surgery in women may depend on a slower evolution of the condition to a degree of disabling deformity or merely reflect a greater tolerance of the deformity by women. - John Hueston 1984

2000 to today
- The average age of onset in men is about 48 years, while in women it is 59 years. Although the disease appears later in women, and is usually less severe, the postoperative complication of chronic regional pain syndrome is double that of men. - Boscheinen-Morrin and Conolly 2000
- Men typically present earlier (mean age 55 years) than women (10 years later) and have more severe disease. - Townley, Baker, Sheppard and Grobbelaar 2006
- Commonly occurring in adults in their 40s to 60s, Dupuytren contracture occurs 10 times more frequently in men than in women. - James H. Calandruccio 2007
- The mean age of onset of the disease [among 60 women] was 50 years and 6 months. Dupuytren’s disease is more uncommon in women and in general, a male-to-female ratio of 5:1 is seen. Although surgical outcome appears to be comparable in men and women, the disease tends to flare up [recur?] more frequently in women. - Degreef, Steeno and De Smet 2008
- Only a few reports in the literature address gender-related differences in terms of incidence, presentation, natural history, and outcome of surgical intervention. The distinctive characteristics of the disease in females are not yet well defined. - Stahl and Calif 2008

26.  I have Dupuytren's disease (Ledderhose disease). Am I likely to get Ledderhose disease (Dupuytren's disease)?

Yes. You are more likely to get it than someone who does not have your disease. The likelihood that you will get the other disease at some point goes up as you age. The probability is not known but is probably greater than 50-50. Having Dupuytren's disease also makes it more likely that you will develop Garrod’s pads (knuckle pads).
If you are male, having either DD or LD is a risk factor for developing Peyronie’s disease.

27.  What are the risk factors for developing Dupuytren’s and Ledderhose disease?

Your risk of getting one of these diseases is greater than average if you:
- are of European descent (perhaps particularly Northern European) 
- are older than 40, and the older you are, the higher the risk that you will develop one of them
- have a relative with the disease
- have Ledderhose, Garrod’s pads or Dupuytren's disease already- have Peyronie's disease
- have ever had a frozen shoulder (adhesive capsulitis)
- habitually drink the equivalent of a bottle of wine a day and have done so for several years. The more you drink, the greater the risk.
- are male (though the main sex-related difference in risk seems to be that the onset of the disease tends to be about 10 years later in women than in men) 
- have insulin-dependent diabetes (and particularly if you are taking insulin or oral hypoglycaemics for diabetes). Diabetic patients tend to have a lower diathesis (that is, a milder form of the disease).

Researchers have suggested a large number of other risk factors, but others have contested them. This list includes cancer, epilepsy (particularly if you are controlling it with phenytoin or phenobarbitone), high cholesterol, heart disease, hypo- and hyperthyroidism, and low body weight and body mass index. 

Chronic liver disease is sometimes cited as a risk factor, but the balance of the evidence from several studies suggests that this is unlikely, when heavy drinking is accounted for. 

Although some studies provide contrary evidence, heavy smoking seems, on balance, to be a strong risk factor, independent of the link between heavy smoking and heavy drinking.

Risk factors only increase the risk of getting the disease. It is conceivable, although improbable, that a teetotal young woman of African descent could develop one of the diseases. But if she did, we could infer that at least one of her ancestors came from a group whose gene pool included alleles linked to the appearance of superficial fibromatosis.

28.  Is it possible that my Dupuytren's disease started because I broke my wrist a few years ago?

Several studies suggest if you carry the genes for the disease, then trauma to the hand or wrist (or foot or ankle in the case of Ledderhose disease) can provoke the disease. Where an injury is thought to have provoked the disease, it typically took place years before the disease appeared.

The link between trauma and the appearance of Dupuytren's disease is difficult to prove, since many people have injured their hands or feet at some point in their lives, and it is not at all clear that a particular injury triggered the disease. 

By analogy, we can be certain that many people developed a migraine sometime in the decade after they read “War and Peace”. If they claim that the book gave them the migraine, we might have our doubts – first, many people who read the book did not get a migraine, and many people with migraines have never read the book. But it is still possible that reading “War and Peace” did indeed give some individuals a migraine. If we found that readers of “War and Peace” were more likely to get migraines than people who had not read it, we would want to know whether people who are predisposed to migraines are also predisposed to reading daunting books by 19th-century Russian authors. 

Back to Dupuytren's and Ledderhose disease; there is some evidence that people with Dupuytren's disease are more likely to have had (or at least to remember) trauma to their hands (often several years earlier) than people who do not have the disease. Unfortunately, we do not know whether people who have injured their hands are more likely to develop the disease. 

In conclusion, while it is not necessary for you to hurt your hand or foot to trigger the disease, there is an increasing body of evidence to show that trauma does sometimes trigger it.

29.  Since my plantar fibromatosis started with an injury, does that mean I can get it in my other foot and possibly hands if they get injured too?

If a trauma triggered the appearance of the disease, it did so because the genetic conditions made it possible for a normal healing process to run out of control. While another trauma could possibly trigger the appearance of the disease in a hand or foot, unfortunately, it seems that no such trigger is needed. 

Many people get the disease without having injured themselves or used vibrating equipment. 
So yes, another trauma could trigger the disease in another place, but it may not wait for that.

30.  What do we know about occupational risk (e.g. vibrating tools)?

A growing body of evidence suggests that the use of vibrating tools for at least 2 hours a day for many years, is a risk factor for Dupuytren's disease. 

For example, in 2012 Professor Alexis Descatha and his co-workers looked at the 13587 employees of Electricité de France (EDF) and Gaz de France (GDF) who answered a questionnaire on their health. Of these 10017 men and 3570 women, 839 men and 160 women said that they had Dupuytren’s disease.
The study looked at a variety of potential risk factors for Dupuytren’s disease. The only significant link was with people who had had “high cumulative occupational exposure to vibration (intensity x duration)” from tools that transmitted vibration to the hands. This included “screw tools, common drills and (infrequently) pneumatic drills, where strenuous hand grip increases vibration damage”. 
They found no relationship between Dupuytren’s disease and jobs that involved carrying loads. 

Other studies have, however, detected an increase in the likelihood of developing Dupuytren's disease and heavy manual labour. 

The pieces of this puzzle will slowly fall into place as more evidence comes in. At present, the link between heavy manual labour and Dupuytren's disease is not clear cut, not least because the disease does not correlate with handedness and seems to develop in either palm irrespective of which hand is dominant.

Unfortunately employers and their insurance companies have a clear vested interest in determining that Dupuytren's disease is not an occupational disease. This means that science is likely to be politicised.

31.  Why do some people call DD "the Viking disease"?

Because they can. Not because it has anything to do with Vikings.
Please refer to two other threads in DART: 
https://www.facebook.com/photo.php?fbid=10204175285197999&set=oa.1642221049334819
https://www.facebook.com/photo.php?fbid=10204577998465579&set=oa.1670344156522508

32.  I don’t know my PIP from my DIP, my metacarpals from my phalanges, my distal from my dorsal. Help!

Palmar means relating to the palm, while plantar means relating to the sole of the foot.
Volar means relating to either the palm or the sole.
Proximal means nearer to the heart, while distal means more distant from it.
Dorsal means towards the back, while ventral means towards the front. In the hand and foot, volar is used more often than ventral.  Radial means toward the thumb and ulnar means towards the little finger.

The hand
The fingers and thumb can be seen as rays coming from the carpal bones that make up the complicated joint of the wrist. In the fingers the rays are clearly separated, but in the palm, they are not, and the metacarpals, the bones in the palm, lie in the same mass of tissue.
There are three bones in each finger. Each bone is called a phalanx. The bone closest to the palm is the proximal phalanx, the next is the middle phalanx and furthest is the distal phalanx. 
The joint between the metacarpal and the proximal phalanx is the knuckle or the metacarpophalangeal joint. 

Each finger has two more joints. The proximal interphalangeal joint, or PIP, is the joint between the phalanges lying closest to the heart - that is, the joint between the proximal and middle phalanxes. The joint nearer the tip of the finger is the distal interphalangeal joint, or DIP. 
Ligaments, tough sheets and cords of collagen, hold the wrist and hand together in a complicated, crisscrossing and overlapping web that resembles, perhaps, a nightmare intersection between 5 highways. Ligaments also hold the interphalangeal joints stable.

Tendons attach to the bone distal to each joint and merge into muscle, either in the palm or in the forearm. The nine long tendons that run from the fingers and palm to the forearm run through the narrow carpal tunnel. This is a passageway on the palmar side of the wrist that is comprised on the volar side by connective tissue and on the dorsal side by bones. Several tendons and the median nerve pass through it. The median nerve also runs through the carpal tunnel and can be compressed if any of the tendons become inflamed.

A long tendon emerges from the carpal tunnel and fans out, becoming a triangle - the strong, thick palmar aponeurosis, lying between the tendons and the skin. The aponeurosis, or fascia, is a tough, flexible sheet of closely packed bundles of collagen fibres organised along the lines of stress - mainly in the direction from wrist to finger. 

The thumb side of the triangle is indistinct, merging into the muscles of the base of the thumb. At its broadest, level with the crook of the thumb, the triangle splits into four tough straps, or slips, one for each finger. The slips are attached to the skin of the palm, to the base of each finger, and to the sheaths of the tendons that flex the fingers. 

The foot
The details of the anatomy of the foot are less important for understanding the disease, and the vocabulary used with Ledderhose is less extensive than the equivalent in the hand.

As in the hand, the foot is supported by thick connective tissue, the plantar fascia or aponeurosis. It is thickest and strongest in the arch of the sole. It starts at the back of the heel (the tuberosity of the calcaneus) and spreads out in a long triangle. At the head of the triangle, level with the beginning of the ball of the big toe, it splits into five thick straps that at their distal ends reach the furthest points of the metatarsal bones, where the bones of the toes begin.

Cells in the fascia called fibroblasts produce, maintain and dissolve the collagen fibres. If you’re reading this, this is the bit of the hand or foot that interests you most, since it is the bit that is involved in Dupuytren’s and Ledderhose disease.

33.  What is known about the genetics?

Not a lot, really. 
- We know that it’s complicated
- we know that there are several genes involved – at least 9 but probably (very?) many more
- we know that you don’t have to have all of them (or perhaps this might be better expressed as "you don't need many of them") to develop the disease
- we know that the genes are on different chromosomes
- we have not found a single one, so far, that is on a chromosome that determines your morphological gender (X or Y chromosomes)
- we know that many of the genes are located near the place in their chromosome where genes are found that control a certain set of processes involved in signalling things to start or stop cells from producing certain chemicals or doing other things.

The bare bones of the story so far are in a photo thread linked at the bottom of this post. 
But first, a little analogy for those who don’t know much about genes, chromosomes and alleles. 
Imagine a library that houses the complete set of instruction manuals that set out all the processes involved in building an Airbus A350XWB. 

First off, it’s huge – there are a very large number of processes involved – so think the warehouse in the final scene of Raiders of the Lost Ark. 

Second, it’s organised by shelves, great long shelves, 44 of them, arranged in pairs back to back, together with one odd pair of shelves. In the analogy, each shelf is a chromosome, and the strange pair are the X and Y chromosomes that determine morphological gender. Each shelf is jam-packed with manuals – some 30 000 in all. 

The manuals are lever-arch files cleverly organised so that each (loose-leaf) page is limited to instructions for a single element of one process – say, making a rivet. 
In this analogy, each page is a gene, and each gene codes for – that is, it provides instructions for – one particular protein (often an enzyme) or part of a protein. 

Here and there on the shelves are manuals that contain special pages that explain when to start obeying instructions from this or that page in some other manual. These are “genetic switches” and are obviously a key to how the entire library – or genome – functions.

Next door is another library, organised in an identical way, except that a tiny proportion of the pages are different from the ones in the first library. Perhaps one-page codes for blue seats instead of cream, or hemstitches rather than blanket stitches in the carpeting. Almost none of these variant pages have to do with fundamental things like rivets or altimeter dials or the twist in the gas turbine fan blades. 
In the analogy, the pages are genes and the variant pages are alleles of those genes. 

Many of these variant pages contain just a single difference – perhaps the only change in the entire page is that the word “sink” is changed to “sunk” somewhere, or “homely” is changed to “comely”, or something is missing from, or added to, one variant, so perhaps “appeal” in one library might be “appal” in the other; and it’s a fairly safe bet that a page giving instructions involving “stamped” is likely to lead to a different process than one that involves “stampede”. 

Thus, by analogy, alleles often code for slightly different enzymes whose behaviour may make the difference between having blue or green eyes or getting and not getting Dupuytren's or Ledderhose disease.

The reason that there are two libraries in this analogy is that every now and then Airbus Industrie decides to take entire sections out of one library and exchange them for an identical section from the other. Identical, that is, except for any alleles that happen to be different in the two libraries. 
At this important and ceremonial event, workers are told to grab huge batches of manuals in a vast armload and swap them with the same manuals in the other library, in order, as a coherent whole. Each manual in the analogy is a group of genes or “recombination block” that tends to stay together whenever anyone reorganises the library – which is to say, when mum and dad’s genes are passed on to their child. (It’s rare that the reorganisation will involve splitting a manual in two but it does sometimes happen. Genes tend to travel down the generations in great clusters, not individually.) 

You’ll have heard that we humans share 99% of our genes with chimps and bonobos. 
You’ll also have heard that your child shares half of your genes. 
It’s more accurate to say that your child gets half of her genes from you and half from her other parent. Almost all of her genes are identical not only to yours and her other parent, but also to any random human or bonobo – and half of them are identical with those in a banana. 

These shared genes typically code for fundamental things - in the analogy, you don't want variants in the pistons that actuate the flaps or the frequencies used by the nose cone radar - and mammals don't need a range of variants in the way neurons signal across synapses. 

This means that all humans are 99.9% genetically identical. 

Roughly half of the remaining 0.1% of your daughter’s genes consists of genes that you share with her, but not with her other parent. That half of 0.1% of her genome (the sum total of her genes) codes for enzymes that will tend to make her resemble you – perhaps in her body shape, her colouration, her aptitude for sport, her susceptibility to dental caries, the shape of her hands and fingers, and whether she might develop Dupuytren's and Ledderhose disease later in her life.

How many genes are involved in Dupuytren's and Ledderhose diseases? And are they the same for both diseases? 

Nobody really knows. One study identified 9 "Dupuytren's" genes on chromosomes 7, 20 and 22; another study suggests that genes on chromosomes 1, 2, 3, 4, 5, 6, 8, 11, 16, 17, 20 and 23 may be associated with Dupuytren’s disease, and chromosomes 6, 11 and 16 “may contain the genes for DD”. Disturbingly, only chromosome 20 is implicated in both studies, which invites the question of how reliable such studies are, and how many other, so far unknown, genes there may be. 

Together these studies suggest that “Dupuytren’s genes” are located on chromosomes 1, 2, 3, 4, 5, 6, 7, 8, 11, 16, 17, 20, 22 and 23 - that is to say on 14 of the 22 autosomal chromosomes carried by humans. At least some of these genes are located close to genes that control important pathways controlling certain kinds of cell behaviour.

- Dolmans, G.H., Werker, P.M., Hennies, H.C., Furniss, D., Festen, E.A., Franke, L., Becker, K., van der Vlies, P., Wolffenbuttel, B.H., Tinschert, S., et al. (2011). Wnt signaling and Dupuytren’s disease. New England Journal of Medicine 365, 307–317.
- Ojwang, J.O., Adrianto, I., Gray-McGuire, C., Nath, S.K., Sun, C., Kaufman, K.M., Harley, J.B., and Rayan, G.M. (2010). Genome-Wide Association Scan of Dupuytren’s Disease. The Journal of Hand Surgery 35, 2039–2045.
Here's the link to another thread that focuses more on the genetics of Dupuytren's and Ledderhose disease:
https://www.facebook.com/photo.php?fbid=10205070836266216&set=oa.1670344156522508&type=3&theater

Are mutations similar?

Genes are sections of DNA. 

DNA is like a spiraling ladder whose rungs are called "base pairs". They're called "pairs" because one half of each rung, which is attached to one side of the ladder, can only be attached to a particular molecule, its pair, which is attached to the other side. 

A short gene may contain about 1000 base pairs, while a long one may be made up of, say, 2.5 million base pairs. Many genes consist of about 10000 to 15000 base pairs.

Genes aren't inherited individually and independently, like a handful of buttons drawn at random from a huge bag. Instead, the buttons are threaded together in long sequences, so when you pull out a handful from the bag, you get entire necklaces of buttons. The genes tend to travel together in these necklaces from one generation to the next.

Genetic evolution happens when one of those base pairs in a gene is substituted for another (a chunk of the ladder is flipped upside down, for example, or a rung is swapped out for another one, or a bit of the ladder is repeated, or cut out, or any other change) and the change is inherited through successive generations and spreads in the population.

Changes like these are called mutations. The word "mutation" comes from the Latin word mutare which simply means "to change". When a change survives and becomes common in a population we talk of alleles of the same gene. "Allele" simply means "version". Most of our genes have a single version - evolution has trimmed away all experiments and come up with a single version of the gene that has proven its worth over all other possible versions. But some genes have one or more alleles.

When scientists look at the genetics of a disease like Dupuytren's, they compare the genes of people with and without the disease. But they have no technical means, as yet, to compare gene by gene. Instead, they pull out "necklaces" of genes from the bag and compare the necklaces of people with the disease to those of people without it.

When they discover that people with the disease are more likely to have a gene necklace that is consistently different from the gene necklace of people without it, they have discovered a genetic link to the disease.

At this point, they look at the necklace they have pulled out and work out where in the DNA it came from. Thus, they can say that people with Dupuytren's disease tend to have a particular marker for the disease (the variety of necklace) at a particular place (within a few tens of millions of base pairs) on a particular chromosome. 

What they can't say, without a huge amount of further research, is which gene along that necklace is different, or what alleles of that gene tend to link with Dupuytren's disease. They'll get to it, but it takes time and effort.

Thus your question, "are mutations similar", has no answer at this point.

34.  How can it be genetic if no one in my family has it?

Imagine a BMW dealership. 

Each year the dealership sends out a questionnaire to all the customers who bought one of the M-range cars - the Coupé, the Gran Coupé, the Sedan, the Convertible, the X5 and X6. One of the questions asks how many speeding tickets the owner picked up this year - these are temptingly fast cars. Each year about 2% of the owners admit to a speeding ticket. 

Every M-range BMW has the capacity to drive very much faster than the speed limit on the fastest road, but the temperament of some drivers makes them invariably obey the speed limit, the luck of others lets them get away with speeding year after year, and the behaviour of others (using radar detectors, perhaps) keeps them out of trouble.

Down the road from the BMW dealership is Mothercare Baby Carriage Co. 

Each year the dealership sends out a questionnaire to all the customers who bought one of the Xpedia Tusk Special Edition baby carriages. The Mothercare questionnaire was designed by the consultant who created the BMW one. One of the questions asks how many speeding tickets the owner picked up this year. Each year 0% of the baby carriages owners admit to a speeding ticket. 

Irrespective of the temperament, luck or the behaviour of the person pushing the baby carriage, they lack the capacity to push fast enough to get into trouble.

In a somewhat similar way, having the alleles that give you the capacity to have Dupuytren’s or Ledderhose disease is not enough. 

You also have to have the temperament, the luck (or lack of it) or the behaviour that triggers the disease (and earns you the speeding ticket). 

So maybe one of your great grandfathers had Dupuytren’s contracture, or a great, great grandmother limped about on Ledderhose-afflicted feet. But none of your ancestors, or their siblings, or your siblings or cousins, had the temperament, the misfortune or the behaviour that triggered the disease - even though they had the capacity, because they had the alleles. 

You, for some reason, had both the capacity and the trigger. Here’s your speeding ticket. Deal with it.
It’s also possible that others in your family did indeed have the disease (or are living with it today) without realising it. 

Study after study shows that the great majority of people with Dupuytren’s or Ledderhose disease do not realise they have it. You might well discover that if you investigate the palms or the soles of all your living relatives, you will be able to tell someone you’re related to that they, too, have over-enthusiastic fibroblasts in the fascia of their palms or soles. Won’t you be popular?

Furthermore, some families may know that they have a genetic disease, but keep quiet about it. Some people see disease as a moral failure. Some people don’t like thinking that their family has a built-in defect. Combine them; admitting that a family is tainted by an inbuilt moral defect is not going to happen.

35.  I have Dupuytren's disease. How do I know whether I have a high diathesis?

In 2011 researchers in the Netherlands looked at the genetics of 933 people with Dupuytren's disease. 
They examined 9 sections of the genome which they had previously found were implicated in Dupuytren's disease. People with the disease are more likely to have abnormal genes in some of these 9 sections than in others, and they used this to create a weighted index of genetic risk for each person. 

They found that people with a high genetic risk index were also more likely than the others 
- to have had Dupuytren's disease start before they were 50, 
- to know other people in the family with the disease, and 
- to have knuckle pads (Garrod’s pads). 

Ledderhose disease was not a good predictor of high genetic risk, even though it was rather more common in people with high, rather than low, genetic risk.

Being a man was not a predictor of high genetic risk, and nor was having the disease in both hands. 
From other work, we know that these factors – early-onset, family history, and knuckle pads – are characteristic of people with high diathesis.

Dolmans, G.H., de Bock, G.H., and Werker, P.M. (2012). Dupuytren Diathesis and Genetic Risk. The Journal of Hand Surgery 37, 2106–2111.

36.  Is Dupuytren's or Ledderhose disease caused by trauma, or is it genetic?

It’s not either/or. But the first point to make is that more is known of Dupuytren's disease than Ledderhose disease in this respect, and the following focuses only on DD.

Whenever people have looked at the genes of someone with Dupuytren's disease they have found alleles characteristic of the disease in one or more of 9 loci on 4 chromosomes. (An allele is a variant of a gene. A locus is a small chunk of a chromosome – locating a gene reasonably accurately is much easier than locating it exactly.) It seems, therefore, that you cannot have Dupuytren's and Ledderhose disease without having alleles that are characteristic of the disease; in short, the disease is genetic. 
The genetics are complex, with some genes contributing more than others to one’s predisposition to the disease. 

Nine genes on 4 chromosomes… what does that mean in terms of inheritance? 

The chromosomes implicated are numbered 7, 19, 20 and 22, with 4, 1, 1 and 3 loci respectively. On chromosomes 7 and 22 the loci are physically close, so will normally be inherited as if they were a single gene. Essentially, then, one can imagine the genetics as 4 genes independently inherited, with 2 of them being particularly potent.

Some rather shaky evidence suggests that the disease can be expressed even if you only inherit alleles from one parent – that is, alleles for the disease are dominant over the recessive non-Dupuytren's alleles. If this is indeed the case then the weakest possible diathesis would be when only you receive only the least potent allele from just one parent. The strongest possible diathesis would be when you receive all of the Dupuytren's alleles from both parents. 

If this model is correct and counting the gene groups on a single chromosome as a single genetic construct, then there are some 200 different combinations of alleles that would predispose you to the disease. 

(You could picture this as if there are 4 normal alleles a, b, c, d and their Dupuytren's alleles A, B, C, D, of which you get one allele from one parent, and one from the other, giving a/a b/b c/c d/D, a/a b/b c/C d/d, through to A/A B/B C/C D/D.) 

If we assume that getting an allele from both parents has an additive effect, and not, say, a multiplicative one, then these 200 combinations give rise to about 30 different levels of diathesis.

Having a genetic predisposition to the disease isn’t the whole story, though. It’s not like having blue eyes, long legs or blonde hair; something has to trigger the disease.

It’s possible that age alone is enough in some cases – something about the changes that take place in the cellular biology as tissues age might conceivably set the disease off. But there are many other possible triggers.

Injury
People often believe that an injury to their hand has caused their condition, and anecdotes abound of Dupuytren's disease occurring in the same place and shortly after an injury.

Dupuytren himself thought that the disease that came to be named after him might be caused by trauma such as that suffered by a wine merchant while he was lifting a cask. As explained in another FAQ, however, it is not easy to establish whether there really is a relationship between injury and disease, particularly when the injury occurred years before the disease appeared.

There is nevertheless some reason to believe that the relationship is real. For example, the creative thinker and hand surgeon John Hueston stated, from long experience, that providing that the person has the necessary alleles, “almost any injury to the limb associated with a period of swelling and disuse of the hand (ranging] from radical mastectomy through proximal limb ruptures, dislocations of shoulder or elbow joints, forearm fractures, superficial burns of the hand, to direct local tissue disruption with hematoma or open wounds and fractures in the hand itself” could presage the onset or worsening of Dupuytren's disease. 

“The palm itself,” he said, “does not have to be the site of the injury.”
He goes on to remark that fasciectomy is an injury to the palm and fingers that is followed by swelling and disuse, and that recurrence occurs “very frequently within a few weeks” of the surgery.
Did the injury cause the disease? Or was it something to do with the swelling and enforced disuse after the injury?

Disuse
One interesting idea that nobody seems to have further investigated was suggested by Hueston in 1990. He observed that a possible trigger was simply sudden disuse of the hand – brought about, for example, by hospitalisation or retirement from a manual job, which could “be followed within weeks by the onset or progress of DD often bilaterally”.

Not Dupuytren's disease at all?
To further complicate an already confused picture, some researchers think that traumatically induced disease of the palmar fascia may not be Dupuytren's disease at all, but something else. In a 2014 paper Findlay and his colleagues claim that these traumatically induced diseases tend to be unilateral and to have no preference for people of any particular ancestry. So far, there has been no examination of the genes of these “non-Dupuytren's” disease cases to show whether they indeed possess none of the alleles typical of Dupuytren's disease.

- Bennett, B. (1982). Dupuytren’s contracture in manual workers. British Journal of Industrial Medicine 39, 98–100.
- Dolmans, G.H.C.G. (2014). The genetic origin of Dupuytren’s disease and associated fibromatosis. PhD. Rijksuniversiteit Groningen.
- Findlay, I., and Tahmassebi, R. (2014). Posttraumatic Disease of the Palmar Fascia. The Journal of Hand Surgery 39, 2086–2088.
- Hueston, J. (1990). Dupuytrens diathesis. In Dupuytren’s Disease Biology and Treatment, R.M. McFarlane, D. McGrouther, and M.H. Flint, eds. (Churchill Livingstone), pp. 246–252.
- Lucas, G., Brichet, A., Roquelaure, Y., Leclerc, A., and Descatha, A. (2008). Dupuytren’s disease: Personal factors and occupational exposure. American Journal of Industrial Medicine 51, 9–15.
- McFarlane, R.M. (1991). Dupuytren’s disease Relation to work and injury. The Journal of Hand Surgery 16A, 775–779.
- Milano, G., Gage, H., and Wilson, C. (1977). An investigation of occupational hand-arm vibration. Bulletin of the New York Academy of Medicine 53, 823.
- Palmer, K.T., D’Angelo, S., Syddall, H., Griffin, M.J., Cooper, C., and Coggon, D. (2014). Dupuytren’s contracture and occupational exposure to hand-transmitted vibration. Occupational and Environmental Medicine 71, 241–245.

37.  What are the benefits of genetic testing? Can I forewarn family members?

If you’ve been diagnosed with Dupuytren's or Ledderhose disease, Garrod’s pads or Peyronie’s disease, you already know that you have one or more of the many genes implicated in these diseases. 

Genetic testing could tell you how many of the genes you have, and although the test can’t determine whether the disease will progress or how fast, it might perhaps give some indication of how high or low your diathesis is likely to be.

If you were to get tested before evidence of the disease appeared in your palm or sole, and discovered that your genome contains alleles for one of the diseases, you might perhaps use the information to keep a regular watch on your palms and soles, and if nodules appeared, go quickly to a radiation oncologist for treatment. 

Genetic testing doesn't substantially increase the information that you might pass on to family members – having the disease yourself means that some of your ancestors also had the genes - and relatives may also have inherited them from those ancestors.

Before submitting to genetic testing, it is important to think about the implications for other people. 
In the countries where Dupuytren's and Ledderhose disease are prevalent, many families have undertaken genealogical studies and placed the results on the internet. Gene testing companies ask you to allow them to make the data public, without identifying who you are. 

Studies have shown that the release even of a few markers can be combined with genealogical data to identify other people who you don’t know, but who are related to you. This means that they share genes with you. Your release of genetic data might therefore reveal genetic information about someone you’ve never heard of – let alone other people in your family. 

- Anderson, E.R., Ye, Z., Caldwell, M.D., and Burmester, J.K. (2014). SNPs Previously Associated with Dupuytren’s Disease Replicated in a North American Cohort. Clinical Medicine & Research 12, 133–137.
- Billings, P.R., Kohn, M.A., De Cuevas, M., Beckwith, J., Alper, J.S., and Natowicz, M.R. (1992). Discrimination as a consequence of genetic testing. American Journal of Human Genetics 50, 476.
- Callaway E. (2012). Ancestry testing goes for pinpoint accuracy Companies use whole genomes to trace geographical origins. Nature 486, 17
- Dolmans, G.H., Werker, P.M., Hennies, H.C., Furniss, D., Festen, E.A., Franke, L., Becker, K., van der Vlies, P., Wolffenbuttel, B.H., Tinschert, S., et al. (2011). Wnt signalling and Dupuytren’s disease. New England Journal of Medicine 365, 307–317.
- Dolmans, G.H., de Bock, G.H., and Werker, P.M. (2012). Dupuytren Diathesis and Genetic Risk. The Journal of Hand Surgery 37, 2106–2111.
- Gymrek, M., McGuire, A.L., Golan, D. Halperin, E., Erlich, Y. (2013) Identifying Personal Genomes by Surname Inference. Science 339: 321-324

38.  Are there any foods that might make the disease worse?

The short answer is “probably not”; there is no uncontested evidence that diet has any impact on the disease. 

Peer-reviewed papers reporting research on diet and superficial fibrotic diseases are as rare as hen’s teeth in the medical literature available on the Web of Science. 

Absence of evidence is not, however, evidence of absence; and absence of evidence has not stopped people touting the value of various dietary supplements. 

The website-based Dupuytren Contracture Institute, for example, will sell you as many pricey supplements as you can swallow. According to his LinkedIn profile, Dr Theodore Herazy, who runs the “Institute”, is a chiropractor. He claims no professional training in either nutrition or Dupuytren's and Ledderhose disease, and it is not clear whether his title “Dr.” is self-awarded or honorific, or whether he actually has academic or medical qualifications that entitle him to it. (You may not know what “chiropractic” is. According to Wikipedia, it is “a form of alternative medicine that focuses on diagnosis and treatment of mechanical disorders of the musculoskeletal system, especially the spine, under the belief that these disorders affect general health via the nervous system.” This background is as good as many others (for example grocer, or politician) to qualify someone to sell dietary supplements for Dupuytren's and Ledderhose disease.)

39.  Does having Dupuytren's disease affect your risk of developing other conditions?

Yes. People with Dupuytren's disease are more likely than those without it to have, to develop or to have had: 

- Ledderhose disease (plantar fibromatosis)
- Peyronie’s disease (penile fibromatosis: by definition, only men need apply)
- Garrod’s pads (knuckle pads, holoderma)
- Frozen shoulder (adhesive capsulitis)
- Carpal tunnel syndrome
- Trigger finger

It seems probable that other diseases that are involved or are provoked by abnormal accumulation of collagen are also associated with Dupuytren's disease.

40.  What are some related fibromatoses?

A fibromatosis is an abnormal, non-cancerous (benign) growth that results in a mass of tissue (a neoplasm or tumour). 

Fibromatoses are characterised by proliferating fibroblasts, growth into and around neighbouring tissue, and the tendency to recur when removed surgically.

Related fibromatosis include plantar, penile and palmar fibromatosis, and holoderma – respectively Ledderhose, Peyronie’s and Dupuytren's disease, and Garrod’s pads.

41.  Should I make sure before having radiotherapy that I have no other underlying issues with my hand or foot, such as arthritis?

Absolutely yes. You should definitely discuss any comorbidities with your doctor and radiation oncologist before going ahead with the treatment.

42.  Why is Dupuytren's and Ledderhose disease more common in people with diabetes?

Diabetes messes up your metabolism in several ways. 

In particular, it encourages sugar to attach to some proteins, which stops them from folding correctly or makes them unstable. It damages nerves and blood vessels and it slows the degradation of collagen, tending to make it accumulate in the skin and fascia. 

This accumulation of collagen seems to be instrumental in causing or starting trigger finger, Dupuytren’s and Ledderhose diseases.

The changes in collagen and connective tissue can trap the median nerve in the carpal tunnel, causing carpal tunnel syndrome, which is common among people with diabetes.

43.  How does RT work to stop Dupuytren's and Ledderhose disease?

Cells in your body have work to do, and they wear out. This means that they have to be replaced, and most cells in your body participate in the replacement cycle by replicating themselves from time to time. Very few of the normal cells in your hand or foot are replicating at any given time; most are in the resting or quiescent phase of the cell cycle of division. That doesn’t mean that they’re resting in terms of their normal function, but they’re resting from the cell cycle of reproduction. 

The fibroblasts in Dupuytren's and Ledderhose disease have got muddled, and they have begun to participate more actively than they should in the cell cycle. This means that not only are they eagerly doing their job of making collagen, but they are also replicating themselves more than they should.
This over-enthusiastic replication is what makes them vulnerable to radiation therapy.

Much of what the cell does is governed by instructions carried in DNA in its nucleus. DNA sometimes gets damaged – particularly by high-energy radiation – and since repairing DNA incorrectly often leads to the death of the cell, evolution has favoured highly conservative, elaborate and effective methods to get it right. Mistakes will happen, however, and cells that repair damaged DNA incorrectly will normally die. 

For a cell to duplicate itself, it has the tricky job of replicating its own DNA. This is a complicated and delicate process involving unzipping the DNA molecule down the middle, copying the two unzipped strands, and zipping them (and copies) up again. DNA carries a lot of information (about 3 billion base pairs, or 3Gb) and this process takes roughly a day, at a rate of about 40 000 base pairs each second.

While this molecular magic is happening, the cell is in a sense on autopilot, unable to follow instructions from the temporarily disabled DNA. Damage to the DNA at this moment is much more difficult to repair accurately than if it happens when the cell is resting. Evolution has developed ways to deal with damage caused during the replication of DNA, but it is inevitably not as reliable as repair work done in other phases of the cell cycle.

We are constantly bathed in radiation – including radio waves, microwaves, thermal infrared, and visible light. These kinds of radiation contain too little energy to ionise tissue that they pass through. 
Some radiation, however, carries so much energy that when it passes through tissue it may tear electrons away from any atoms that it collides with. Energetic radiation of this kind can be carried by the high-energy photons that we call x-rays or gamma rays, and by high-energy sub-atomic particles such as electrons, protons, neutrons and carbon ions. 

Life has evolved to deal with ionising radiation of this kind – we are bathed in small quantities of this radiation from the sun and from various exotic sources in space – but not too much of it. Cells damaged by ionising radiation can repair themselves, even when the damage happens to the DNA, but are at their most vulnerable when replicating themselves.

Radiotherapy works by creating high-energy, ionising radiation, and pointing it at the problematic tissue, usually a neoplasm or tumour. This ionising radiation damages many of the cells in the tissue, but while quiescent cells can usually repair damage to their DNA, replicating or proliferating cells find it much more difficult, and are the damage often proves lethal. 

Radiation therapy is gauged to kill replicating cells while doing as little damage as possible to the quiescent cells. Since Dupuytren's and Ledderhose disease are characterised by proliferating fibroblasts, the therapy is designed to single out these replicating cells and kill them, while damaging the normal cells as little as possible.

The most common protocol for Dupuytren's and Ledderhose disease divides the total dose of radiation into two series of 5 days each. 

Why? 
Radiation may take time to kill cells, and sometimes it takes days of treatment for cells to start dying. Furthermore, since the phase of replicating the DNA takes about a day, by fractionating the dose over several days, fibroblasts that were quiescent but then begin to replicate may be caught on the hop. 
This explains why each series is divided into 5 days – maximising the chance of catching the fibroblasts at their most vulnerable. 

But some fibroblasts may remain quiescent throughout the 5 days, and, like other quiescent cells, quietly repair any damage they suffer to their DNA. The second series of 5 days, two, three or four months later, is intended to catch any surviving fibroblasts when they, too, begin to replicate.
The damaged cells may keep dying for months after the treatment. This is why the full effect of the treatment may take months to make themselves felt, and also why side effects (including sore skin and tiredness) sometimes appear long after the end of the treatment.

Some clinics offering radiation treatment for Dupuytren's and Ledderhose disease use x-rays generated by a relatively low energy (250 kV) radiation source called orthovoltage units. This kind of radiation delivers most of its energy at the surface of the target and successively less as it penetrates the tissue. To prevent damage to the skin, a bolus is laid on top of the area to be irradiated so that the dose at the skin is not much higher than the dose delivered to the nodules beneath its surface. The x-ray photons ionise tissue all the way through the hand or foot, but the beams are designed to deliver the highest intensity in the nodules.

Higher energy x-rays (1-20 MV) from megavoltage linear accelerators deliver most of their energy beneath the surface of the target. For this reason, a bolus is not normally used by the clinics that offer megavoltage treatment for Dupuytren's and Ledderhose disease.

Linear accelerators with higher energies (>6 MV) can also produce beams of electrons or heavier particles.

Electrons don’t penetrate far, depositing most of their energy in the first centimeter or two below the skin, making them ideal for treating Dupuytren's and Ledderhose disease. Because electrons scatter in air, the machine that delivers them is fitted with a cone that guides (or collimates) the beam. The cone, which almost touches the skin surface, is a give-away that electrons are being used.

Protons cause little ionisation as they pass through tissue, until they reach the end of their path where they release all their energy. This allows the practitioner to deliver almost all the dose to the target tumour. Very few clinics own the highly specialized linear accelerators that generate proton beams.

Some clinics use an IMRT (Intensity-modulated radiation therapy) machine to irradiate the nodules. This is currently the most technologically advanced machine for providing radiotherapy. It uses a computer-controlled linear accelerator to move around the target in such a way as to deliver radiation directly to the nodule, with minimal radiation passing through any given area outside the target. 

To achieve this result, the nodule must not move relative to the head of the machine during the process and must be in exactly the same place from one day's treatment to the next.

This means that you will start your therapy with a simulation during which your radiation oncologist will position your hand or foot and scan it with computed tomography (CT), magnetic resonance image (MRI), or an x-ray. This will allow them to locate the nodules and cords and direct the radiation beam appropriately. 

The radiation oncologist may tattoo your hand or foot with a small dot to ensure that the hand or foot is always precisely in the same place relative to the radiation beam. 

They will then create a mould or foam sponge to hold your hand and fingers in exactly the same position each time. 

With other kinds of machines that do not have the same precision, the team will either use a standard shield or design a personalised shield to ensure that the radiation is confined to the nodules and cords in your hand.

Clinics that do not use computer-controlled machines want to provide a radiation field that includes all of the nodules and cords and extends beyond them for 1 or 2 cm to try to ensure that diseased tissue that has not yet formed nodules is included. Under these circumstances, a personalised shield is unnecessary and a generic one will do. 

Since the exact position of the target is not crucial, the oncologist will position the hand or foot during the first session, photograph it in place, and use that photograph to position the hand or foot in subsequent sessions. 

In these clinics, the first session is not a simulation.

Radiation therapy is completely painless.

44.  If radiotherapy delays progression of the nodules in around 75 per cent of patients, what about the other 25 percent?

The best data we have come from Seegenschmiedt, M.H., Keilholz, L., Wielpütz, M., Schubert, C., and Fehlauer, F. (2012). Long-Term Outcome of Radiotherapy for Early Stage Dupuytren’s Disease: A Phase Ill Clinical Study. In Dupuytren’s Disease and Related Hyperproliferative Disorders, C. Eaton, M.H. Seegenschmiedt, A. Bayat, G. Gabbiani, P. Werker, and W. Wach, eds. (Berlin, Heidelberg: Springer Berlin Heidelberg),.

In this study, 122 people opted not to get radiotherapy. 293 received 21Gy spread over 7 days in a single series, and 303 received 30Gy in two series of 5 days each. I’ll call these no, single and double treatments. 

At the start of the study, the status of the disease was assessed as 
- nodules
- slight contracture (up to 10º) 
- contracture between 10º and 45º
- contracture beyond 45º

For comprehension I’ll call these four classes “nodules”, “slight”, “mid”, and “marked” contracture.
At the start of the study, the group that opted for no treatment comprised 76 people with nodules, 26 of whom (34%) saw their disease progress to slight contracture or further in the course of the 5 or more years following treatment. The group who had single treatment comprised 195 people with nodules, of whom 14 progressed (7%) and the double treatment group comprised 199 people with nodules, of whom 7 progressed (4%).

The no treatment group comprised 21 people with slight contracture at the start, of whom 14 progressed (67%). 50 single treatment people had slight contracture, and 21 progressed (42%). 16 of the 53 double treatment people saw their disease progress from slight contracture (30%).
Of the 16 people with mid contracture, 14 progressed (88%). 25 of the 43 single treatment people progressed (58%) and 23 of the 47 of the double treatment progressed (49%).

All 9 of the no-treatment people with marked contracture progressed (100%). 4 of the 5 single treatment progressed (80%) and 3 of the 4 double treatment progressed (75%).

In every case the people with no treatment progressed more often than people with a single treatment, who in turn were more likely to progress than the people with double treatment. 

Similarly, in every case, the more advanced the disease at the start of the study, the more likely it was for the disease to progress.

If you have nodules now, then if you do nothing, these results suggest that you have 1 chance in 3 of seeing your hand get worse over the next 5 years. 

If you go for radiotherapy, you have 1 chance in 20 of it getting worse. 
If that therapy consists of 2 series of 5 days each, you have 1 chance in 25. A no-brainer if ever there was one.

The message is clear: get radiotherapy as early as you can and get 30Gy in two series of 5 days each. It won't necessarily work in your case, but you're doing something to decrease the probability of your disease progressing in the next 5 years.

45.  Can I expect any remission (improvement of function, reduction of the size or hardness of the nodules, etc) as a consequence of RT?

The desired endpoint of radiation therapy is (a) to stop the progress (or at least delay it by several years) and (b) to reduce or stop the pain and itching.
 
Nobody claims that radiotherapy will reliably reverse the progress of the disease, or give you back lost functionality. It does sometimes happen, possibly more often with Ledderhose disease than with Dupuytren's disease, but if you don’t expect it you won’t be disappointed.

If it does remit, then the underlying question is, as always: would it have got better without the radiation? And here the answer is, really, we don’t know. 

There is evidence of cases of Dupuytren's nodules disappearing of their own accord, but the medical literature isn’t brimming with examples. Instead we must rely partly on glimpses like this:
“The usual chronic form develops over months or years and may show exacerbations and remissions.”
Gordon, S. (1948). Dupuytren’s contracture. Canadian Medical Association Journal 58, 543.
“In nine hands during the period of observation there was temporary involution of nodules or bands originally present in the hands. Given an adequate length of observation time, no case of involution was permanent.”
Millesi, H. (1974). The Clinical and Morphological Course of Dupuytren’s Disease. In Dupuytren’s Disease, J. Hueston, and R. Tubiana, eds. (London: Grune & Stratton),
and
“My mentor, Professor E. S. J. King, perhaps Australia's greatest surgeon-pathologist and acute observer of the metaplastic potential of connective tissues, was adamant that he had in his own right palm a nodule of Dupuytren's contracture which disappeared after a few years.”
Hueston, J.T. (1992). Regression of Dupuytren’s contracture. J Hand Surg Br 17, 453–457.
The best, and most hopeful, evidence of remission comes from a study involving 193 men (there is no explanation of why only men participated) in Iceland. 

At the start of the study in 1981, 75 men had nodules and cords (but no contracture). 
Of these 75 men, 8, that is to say almost 10%, had no sign of Dupuytren's disease 18 years later. 
Two of the 12 men with contractures had lost them over the same period, but still had nodules and cords.

Gudmundsson, K.G., Arngrímsson, R., and Jónsson, T. (2001). Eighteen years follow-up study of the clinical manifestations and progression of Dupuytren’s disease. Scandinavian Journal of Rheumatology 30, 31–34.

46.  What percentage of people with Dupuytren's disease will eventually contract? I've read the Q&A, but have gotten two different ideas. It's either 2% or 34%. Would you clarify?

An excellent question, and one that naturally preoccupies all of us who have the disease.
There are probably four main reasons for the discrepancy in the quoted rates of progression.

First, the natural history of Dupuytren's disease is confusing. 

The disease seems to be highly dependent on the person in which it is developing and the medical literature contains many statements to the effect that “the speed at which Dupuytren’s contracture progresses is variable from case to case.” 

It’s conceivable, too, that what we think of as “Dupuytren’s disease” is in fact a family of diseases with similar manifestations, each disease typically progresses at different rates.

Second, there is no single agreed method of assessing the degree of severity or progression of Dupuytren's disease. 

Methods described and used in the medical literature include: the location of the disease, the extension of the disease and cord patterns; the 1st web angle; the range of movement or arc of motion (either active or total), the degree of active extension at the PIP joint, the degree of contracture (e.g. flexion deformity, Tubiana score), the degree of loss of extension (e.g. fixed flexion deficit), the joint angles (e.g. degree of MCP fixed flexion, degree of PIP contracture), collagen levels, histology, functional limitations (e.g. Swanson impairment grade, Sollerman score), loss of sensation (e.g. Semmes–Weinstein monofilament test), and patient evaluation measures (e.g. DASH).

This profusion of measurement scales makes it extremely difficult to compare studies, which is a problem when it comes to studies that report on the natural history of the disease – and especially the rate of progress of the disease.

Furthermore, methods are often modified, making comparison more difficult. For example, the Tubiana scoring system assigns hands to classes depending on the presence or absence of nodules, and contracture of the fingers measured in degrees.

By way of illustration, we can take three studies that refer to Tubiana’s grading system.

Tubiana’s original paper says, for each finger,
“Stage 0 corresponds to a nodule or band with no contracture.
Stage I contracture between 0 and 45 degrees
Stage II contracture between 45 and 90 degrees
Stage III contracture between 90 and 135 degrees
Stage IV contracture greater than 135 degrees
These stages correspond to increasing difficulty in surgical correction.”
These stages relate to individual fingers. The paper suggests that an index for the whole hand can be generated by adding the scores for each finger, scoring 0.5 for stage 0, then 1 to 4 for stages I to IV respectively.
Tubiana, R., Michon, J., and Thomine, J.M. (1968). Scheme for the Assessment of Deformities in Dupuytren’s Disease. Surgical Clinics of North America 48.

Another study refines the early stages of the disease by adding an intermediary stage:
Stage 0: no (apparent) lesion
Stage N: nodes without flexion deformity
Stage N/I: nodes with flexion deformity 1-5°
Stage I: nodes with flexion deformity 6-45°
Stage II: nodes with flexion deformity 46-90°
Stage III: nodes with flexion deformity >90°
[Stage IV is not defined]
The paper does not clarify whether the “whole hand” index was used.
Keilholz, L., Seegenschmiedt, H., and Sauer, R. (1996). Radiotherapy For Prevention Of Disease Progression In Earlystage Dupuytren’s Contracture- Initial And Long-Term Results.

The same authors, writing 16 years later, redefine their refined early stages:
Stage N: Nodules, cords, skin retraction and fixation, etc., no flexion deformity
Stage N/I: As stage N plus deformity of fingers 1-10°
Stage I: As stage N plus flexion deformity of fingers 11-45°
Stage II: As stage N plus flexion deformity of fingers 46-90°
Stage III: As stage N plus flexion deformity of fingers 91-135°
Stage IV: As stage N plus flexion deformity of fingers > 135°
Seegenschmiedt, M.H., Keilholz, L., Wielpütz, M., Schubert, C., and Fehlauer, F. (2012). Long-Term Outcome of Radiotherapy for Early Stage Dupuytren’s Disease: A Phase Ill Clinical Study. In Dupuytren’s Disease and Related Hyperproliferative Disorders, C. Eaton, M.H. Seegenschmiedt, A. Bayat, G. Gabbiani, P. Werker, and W. Wach, eds. (Berlin, Heidelberg: Springer Berlin Heidelberg).

The third reason for a discrepancy in reported rates may be that different populations have different typical levels of diathesis. Perhaps a population with a high frequency of alleles that strongly predispose their owner to Dupuytren’s disease will tend to exhibit faster progression than others.

The fourth and perhaps most important reason for a discrepancy in reported rates is that, while the literature contains many statements like, “Dupuytren’s tends to progress more rapidly in men than in women and in those who have both hands involved”, there are very few studies of the natural history of the disease to confirm, far less put any numbers on, these generalities.

But there are some data. 
Three main sources are:
Gudmundsson, K.G., Arngrímsson, R., and Jónsson, T. (2001). Eighteen years follow-up study of the clinical manifestations and progression of Dupuytren’s disease. Scandinavian Journal of Rheumatology 30, 31–34.
Millesi, H. (1974). The Clinical and Morphological Course of Dupuytren’s Disease. In Dupuytren’s Disease, J. Hueston, and R. Tubiana, eds. (London: Grune & Stratton)
Seegenschmiedt, M.H., Keilholz, L., Wielpütz, M., Schubert, C., and Fehlauer, F. (2012). Long-Term Outcome of Radiotherapy for Early Stage Dupuytren’s Disease: A Phase Ill Clinical Study. In Dupuytren’s Disease and Related Hyperproliferative Disorders, C. Eaton, M.H. Seegenschmiedt, A. Bayat, G. Gabbiani, P. Werker, and W. Wach, eds. (Berlin, Heidelberg: Springer Berlin Heidelberg).

All three used different thresholds to describe the stages of the disease.

Gudmundsson: “The hands of all participants were clinically examined for signs of the disease and graded into two stages. 
Patients with stage 1 had palpable nodule(s) in the palms, while patients with stage 2 had contracture of the fingers or had been operated on for contracture.” [i.e. 0°, >0°] 
Findings: Roughly 2% of men without symptoms developed nodules each year, and 1% developed contractures. Of those who already had nodules, about 2% per year developed contractures.

Millesi: [inferred from a graph] 0°, 1°-30°, 31°-90°, >91° contracture. The time since the start of the disease was determined by asking the person how long ago they first noticed the disease.
Findings: From the data provided in the graph, it would appear that about 7% of people in the sample went from nodules but no contracture to some degree of contracture each year. 
This finding must be treated with caution, however, since most people with symptoms of Dupuytren's disease do not know that they have it. This means that the 5 to 12-year span suggested by the graph might be much longer, bringing the apparent 7% per year down to an unknown extent. 
According to this study, once contractures start, progression to a more severe contracture seems rapid, with almost everybody developing a worse contracture in about 2 years.

Millesi states that the “average duration of the pathological changes was as follows:
Stage of fibre thickening 4 years
Stage of cell proliferation 5.7 years
Stage of fibre production 6.2 years
Fibrous stage 7.6 years
Secondary cell proliferation 10.3 years”
The paper also has interesting data on how likely it is to get Dupuytren's disease bilaterally if one has it in one hand. He says,
“In a further study the fate of 113 hands was followed, in which at the first examination there were no signs of the disease. The patients were being treated for Dupuytren's disease in the contralateral hand. In the course of time a proportion of the hands originally free of the disease became affected to the following extent:
With an observation time of 5 years: 39%
With an observation time of 6 to 12 years: 48%”

Seegenschmiedt: 0°, 1°-10°, 11-45°, 46-90°, 91-135°, > 135°
Findings: 26 (34%) of 76 people who did not receive radiotherapy progressed from nodules to some contracture in the course of the 5 or more years of the study. This might suggest that about 7% of them progressed each year. 
Of the 21 people with slight contracture at the start, 14 (67%) progressed, suggesting about 15% of them progressed each year.
All 9 of the people with marked contracture progressed (100%).

Taken together, these results suggest that without treatment, out of a population of 100 people with nodules in their palm at the start of the year, somewhere between 2% and 7% will have developed contractures by the year’s end. 
Out of a population of 100 people with contractures at the start of the year, 15 or more – perhaps many more – will find their contracture worse at year’s end.

So, what is the answer to the initial question: What percentage of people with Dupuytren's nodules will eventually contract? 

The data seem to suggest that if those people live for another 15 or 20 years, all of them will develop contractures. The story is unlikely to be that simple, however, since some people will have a very low diathesis and their disease may spontaneously remit, or become quiescent and they will not develop contractures at all. Others, with a high diathesis, will find their hands contracting very rapidly.

How about a rather over-dramatic analogy to end this FAQ? It seems that without treatment, having Dupuytren's nodules in your palm is a kind of Russian roulette – played once a year, with a revolver that has 1 bullet and an unknown number of chambers, possibly between 10 and 50 of them,
This, of course, is why surgeons tell you to wait. If there really are 50 chambers in the revolver, on average, 25 years will pass before the hammer hits a live round. If you're already, say, 55 years old - well, you do the math.

47.  Can RT cause cancer?

Not a single cancer has ever been attributed to radiotherapy for Dupuytren’s or Ledderhose disease. 

Not one. 

All ionising radiation can damage the DNA of a cell in such a way that the cell, having repaired the damage incorrectly, becomes cancerous. But this risk of radiotherapy for Dupuytren's and Ledderhose disease is entirely theoretical so far. 

The theoretical increase in risk is about 0.02% if you are 60 when you get the radiation treatment, and it doubles for every decade younger, so if you are 50 it's about 0.04%, 40 0.08%, and 30, 0.2%. 
Now this means that instead of running a risk of say 35%, you're up to 35.2% if you are 30 when you get the treatment. In other words, the increase in risk is not zero but it is negligible.

In fact, there is some evidence that having Dupuytren's or Ledderhose disease may be linked to a higher risk of cancer – and the radiotherapy has nothing to do with it. 

About a quarter of all deaths in the industrialised countries are from cancer - that is, about 25%. A small number of studies suggest that people who have had surgery for Dupuytren’s or Ledderhose disease are more likely to die of cancer than people without the disease - about a third, say 35%. 
So there's a possible link between these diseases and cancer but we don't understand it.

48.  Does RT hurt?

If you’ve ever had an X-ray you know exactly how much it hurts – not at all.
But there may be some pain after the treatment - see https://www.facebook.com/photo.php?fbid=10204691165734690&set=oa.1670515403172050

49.  Is RT effective at all stages of the disease?

There’s clinical evidence that the earlier the treatment, the better the result.

In general, most radiation oncologists would probably be reluctant to recommend it after contracture has set in, and particularly once it’s past about 10°.

Radiation therapy is sometimes recommended after surgery to reduce the contracture. In this case the purpose is to prevent over-active fibroblasts from quickly re-establishing the cord. There is, as yet, no peer-reviewed study that provides evidence on the degree to which this improves matters.

50.  "Radiation" is a scary word. How is this treatment different than radiation given to a cancer patient?

“Radiation” is associated with frightening things like nuclear bombs and accidents at nuclear power stations. 
We can’t perceive it. 
We can’t see it or smell it or taste it or feel it. 
It penetrates our body and causes unfelt damage, leading to terrible burns, cancer, mutations, radiation sickness, and death. 
Even when it’s used therapeutically, it works by damaging and killing cells. 
Technicians stand behind thick lead shields. 
So yeah, it’s scary.
So why do we use it? 
Because it can stop the progress of cancer by killing the cancer cells and can stop or slow the progress of Dupuytren's and Ledderhose disease. 
And because it can do those things without causing burns, cancer, mutation, sickness or death. 
A little vocabulary: Grays measure absorbed radiation; 1Gy is one joule of energy absorbed per kilogram of matter. 1 mGy is one milliGrey, or one thousandth of a Gray.
Medical X-rays and scans use very low doses of radiation - around 1-10 mGy.
 
Therapeutic radiation is delivered at thousands of times higher doses - preventive doses may be around 50Gy, while curative doses are often around 70Gy. Lymphomas, Dupuytren’s and Ledderhose disease are typically treated with 20 to 30 Gy. 

You may read statements or see charts showing that if a human is exposed to 5Gy or more they will usually die in less than a month. 

So how can Dupuytren's and Ledderhose disease be treated with 30Gy? It’s because the lethal 5Gy is absorbed in a single dose by the whole body. If the person concerned weighs 75kg, then they absorb 5x75=375 joules of radiation.
 
The weight of tissue irradiated in Dupuytren's or Ledderhose disease is perhaps 100g, or 0.1kg, so the total energy absorbed amounts to 30x0.1=3 joules of radiation. This is normally fractionated into 2 series of 5 sessions, giving 0.3 joules at each session. 

Thus, the damage provoked by the lethal 5Gy (corresponding to 375 joules) is 1250 times greater than that of one of the therapeutic sessions (consequent on 0.3 joules).
Dangerous? Perhaps, but we live in a world of dangerous things like cars and banks and avian flu. You deal with dangerous things all the time. They haven't killed you yet.
Scary?
Not so much.

I should add that the cells that are irradiated do not become radioactive. This means that blood cells that happen to be irradiated do not carry any trace of radiation away from the irradiated area.

51.  What are doctors’ thoughts on re-radiating the same area?

Some radiation oncologists would not even consider it. Others, who would consider it, would treat each case individually, but their prevailing attitude is one of caution.

Here's a doctor's recent response

https://www.facebook.com/groups/1622748151282109/permalink/1714895302067393/

Re-irradiation for Dupuytren's/Ledderhose disease:

I've not written before about re-irradiation, so here are my thoughts: 
1. There are a few clinical details to take into account when considering it a. The amount of time between the first RT and the recurrence - if it is a short interval then it would seem less likely for the RT to be effective. 
b. The amount of recurrence, and symptoms associated with it. 
c. The overlap between the initial and the subsequent RT field - if minimal, then could better justify. 
d. The initial RT reaction - if more severe then may indicate less tolerance of re-irradiation. 
2. The re-irradiation area - should be minimal - basically recurrent disease with a low margin. 
3. Type of RT - I'll be controversial, but my opinion is that where available it would be best with low-energy (superficial) RT, as need less of a margin, although some oncologists may worry about the bone dose (I don't) 
4. Dose of RT - I would stick to 15 Gray in 5 fractions over 1 week. The cumulative dose is "okay" for skin, but I do worry about potential long-term side-effects, which could include skin ulceration, which is why I've shied away from doing it. 
5. Bear in mind that there is nothing published on this in the literature.
I would be interested to hear your comments or questions. Regards, Richard Shaffer

52.  Am I likely to have any side-effects from radiation therapy?

Most people have few or no side-effects, but the relative risk of side-effects seems to be linked to the protocol used. 

The body can deal with a certain amount of radiation in a certain time, but the higher the dose and the shorter the time over which it is absorbed, the more likely it is that the body will react badly – that is, display side-effects. If you receive 30Gy in two series, perhaps split over 8 weeks, your body has time to recover from the first 15Gy pulse before facing the second one sometime later. If you receive 21Gy in a single series lasting 7 days, although your body has to deal with 3Gy a day as before, the assault on your tissues is sustained for longer in that single series. This tends to increase the risk of unwanted side-effects.

The use of the word “risk” acknowledges that there is no hard and fast rule and that everyone reacts differently.

The most widely-shared side-effect is tiredness. This, almost certainly, has little to do with the radiation itself, since only a very small area of your hands or feet is being radiated, but it is much more likely that it is related to the circumstances around the treatment. Your routine is changed, you have to be at a certain place at a certain time each day, you have to travel to get to the appointment, you may have had to travel to, and be in an unfamiliar city, and you may have to live in a hotel or stay with friends during the treatment. To add to that you may quite naturally feel anxious about the treatment and concerned about whether it will work for you. Tiredness is natural.

Many people notice a sensation of heat in the radiated area, rather like that of sunburn, after a few days of treatment. Your skin may turn red and feel dry and tender, again as if you had a mild sunburn. This set of symptoms may last for a couple of weeks after the therapy, and it may even intensify for a while in the days after the end of the treatment. This reaction is exactly analogous to that of sunburn. Sunburn is caused by overexposure to ultraviolet light, which is highly energetic, and damages tissues in and under the skin. The machine used to provide your radiation therapy does not use ultraviolet, but much more energetic radiation, and works by damaging the fibroblasts that are running out of control. It also, inevitably, damages normal cells. The “sunburn” symptoms are those of tissues reacting to high doses of extremely energetic radiation. The symptoms may continue after treatment because the tissues will not fully recover for several weeks. 

Other symptoms that are commonly encountered by people undergoing radiation therapy for cancer include hair loss, nausea, frequent urination, and diarrhea. None of these side effects has been reported for people receiving therapy for Dupuytren's or Ledderhose disease.

Your treatment is designed to give as few side-effects as possible. For this reason, it is unlikely (though not impossible) that you will experience some long-term, or even permanent, changes.

You may notice that the skin in the treated area seems to have a permanent suntan, or creases in the palm may take on a deeper colouring, veering towards magenta. The skin may feel harsher and less elastic than it was. In some unfortunate people, radiotherapy may cause radiation fibrosis, where the tissues become less stretchy. This is problematic for patients who have had radiation therapy involving organs such as the heart, liver or lungs, but much less likely to be problematic for patients treated for Dupuytren's and Ledderhose disease, whose tissues of the radiated area are in any case less stretchy than they should be.

You may also notice that the nodules and cords become better defined, and perhaps more tender to the touch, after radiation therapy. Before the therapy, the areas around the activity of the disease are inflamed and puffy. This swollen tissue masks the outline of the nodules and cords. After the radiation, the inflammation disappears, and the nodules become more easily felt beneath the skin.

Some people experience a period of increased pain in the irradiated areas, sometimes lasting several weeks. It’s not very clear why this happens, but one suggestion is that nerves that had become surrounded by and embedded in the collagen laid down by the disease are triggering as the inflammation around them decreases.

There is not a huge amount of evidence in the medical literature on side effects of radiation therapy for Dupuytren's disease, and as far as I know nothing at all on Ledderhose or Peyronie's disease. The following excerpts are typical.

[Erythema = reddening of the skin
Desquamation = peeling
Atrophy = shrinking and thinning (wasting away)
Teleangiectasia = reddish clusters or spidery marks caused by dilatation of the capillaries
Sarcoma = malignant cancer of the soft tissues]
Erythema of the treated area was reported in 42 patients (20.4%) and no data were available for 27 patients (13.1%). Dryness of the treated skin was present in 82 patients (39.8%) and no data were available for 15 patients (7.3%). Desquamation was reported in eight patients (3.8%).
Chronic side-effects that persisted for more than 4 weeks after the end of the treatment were dryness of the skin (41 patients, 20%), skin atrophy (seven patients, 3%), lack of sweating (eight patients, 4%), teleangiectasia (six patients, 3%), desquamation (five patients, 2%) and sensory affection (four patients, 2%).
Zirbs, M., Anzeneder, T., Bruckbauer, H., Hofmann, H., Brockow, K., Ring, J., and Eberlein, B. (2015). Radiotherapy with soft X-rays in Dupuytren’s disease - successful, well-tolerated and satisfying. Journal of the European Academy of Dermatology and Venereology 29, 904–911.

An estimate of the statistical risk of lethal skin cancer caused by RT at age 45 for Dupuytren's disease is provided by the International Dupuytren Society in collaboration with the German Centre for Environmental and Health Research. In patients exposed to RT for Dupuytren's disease (30 Gy low energy fractionated X-rays) the risk is estimated to be about 0.02% higher than the probability of dying from cancer without RT (estimated to be -24 ± 0.26%). Since the excess risk is very small compared to the background risk it is impossible to evaluate this accurately in a clinical study.

It should be noted that the risk is subject to a number of assumptions. In particular it is calculated for one hand, so the risk doubles if both hands are treated. The calculations are based on an irradiated area of 60 cm2, which is fairly large, so the risk is reduced if the irradiated area is smaller, and it assumes that the remaining hand and body are sufficiently protected during treatment. The risk estimate is also affected by the age of exposure to RT treatment. For a patient of 25 years the risk is approximately double that of a 45-year old and it is about half for an individual receiving treatment at age 60. Although rare, Dupuytren's disease can occur in children and young adults. Clearly their risk of radiation-induced cancer (RIC) will be increased further so RT should only be used alongside careful counselling of the patient.

The above estimate applies to the risk of a fatal radiation-induced skin cancer. There may also be a risk of sarcoma; this is difficult to assess but is likely to be less than the risk for skin cancer. One factor which may affect the risk in an unknown manner is the reported higher risk of dying of cancer in individuals with Dupuytren's disease. As discussed in the section on the risk of a radiation-induced malignancy following low to moderate dose radiotherapy, a recent study has modelled the risk of a range of cancers arising from radiation exposure for benign disease using male and female anthropomorphic phantoms. Although not exactly comparable, the calculated risk was similar to the above estimate. To the authors' knowledge, not a single case of cancer caused by radiation therapy for Dupuytren's disease has been reported in the literature.

It should be noted that there are other more immediate effects that, although less serious than cancer, have a greater probability of occurring. For example, in a long-term follow-up of 176 radiated hands, 25% exhibited anhidrosis, 8.5% skin atrophy and >1% reduced wound healing.
Anon (2015). A review of the use of radiotherapy in the UK for the treatment of benign clinical conditions and benign tumours (UK Royal College of Radiologists).

[The following text relates mainly to radiation used in the treatment of cancer.]
Treatment reactions reach their peak approximately ten to 14 days after treatment completion. After this time the skin reaction will gradually reduce as the basal cell layer recovers and normal equilibrium between cell death and cell reproduction returns to the epidermis.

While most skin reactions heal over time, some patients may experience long-term skin changes that appear months or years after treatment. These include:

■ Changes in pigmentation due to the effect of radiation on melanocytes.
■ Decreased tissue flexibility affecting range of motion and tissue strength caused by the effect of radiation on the supporting structures in the dermis.
■ The appearance of spidery red lines, called telangiectasia, caused by damage and stretching of the capillary blood vessels during treatment.
■ Impaired wound healing in the treated area.

Factors influencing the severity of skin reactions 
While skin reactions are one of the most common side effects of external beam radiotherapy, the severity varies between patients due to a wide range of factors. This means that it is not always possible to predict in advance the severity of skin reactions that an individual may experience. However, knowledge of the risk factors can help staff develop appropriate individualised evidence-based care.
Influences on radiotherapy skin reactions can be divided into extrinsic and intrinsic factors. Extrinsic factors are those related to the treatment process, while intrinsic factors are those related to the patient.
Extrinsic factors Treatment dose and volume Severity of skin reactions are affected by the cumulative treatment dose.
Skin reactions tend to appear in the second and third week of treatment and their incidence increases as treatment continues. Patients having palliative radiotherapy at doses less than a total of 2000cGy are at reduced risk of skin reactions.
Size and location of the treatment field Reactions are greater in larger and/or irregular shaped treatment areas where it is more difficult to achieve an even dose across the field.
This can be seen in radiotherapy to the breast, where women with larger cup sizes of D or above tend to have more severe skin reactions than women with smaller breasts
Skin folds and treatment sites with increased potential for friction and/or moistness are also associated with more severe skin reactions. This includes the axilla, under the breast, head and neck, perineum and groin.
Fractionation Radiotherapy is often delivered in small doses each day over a period of time; this is called fractionation. Delivering treatment this way increases the chances of killing cancer cells when they are more sensitive to the effects of radiotherapy in the mitosis phase. These smaller daily doses also allow normal cells to recover and repair from sub-lethal damage, therefore reducing toxicity. Different fractionation schedules influence the incidence, timing and severity of skin reactions.
Treatment technique Different techniques are used to plan and deliver radiotherapy and the technology used is continually evolving to improve treatment accuracy. The use of intensity-modulated radiotherapy (IMRT) has been shown to reduce the incidence of long-term effects and plans are in place for its use to be increased in the UK.
Warnock, C., and Lee, N. (2014). Skin reactions from radiotherapy. Cancer Nursing Practice 13, 16–22.

53.  What might happen to the skin where I'm radiated?

You may see some changes during and for some time after the radiation.

The skin is constantly renewing itself. Dead cells slough off the top of the skin, and new cells form at the base of the epidermis. Between the epidermis and the top of the skin lies the dermis, which contains blood vessels, glands, nerves and hair follicles, and provides the structure that allows the epidermis to renew itself, a process that normally takes about 4 weeks, or a bit less when the skin is healing.

Because cells in the basal layer of the epidermis proliferate rapidly, this layer is particularly sensitive to radiotherapy. It also lies very close to the target cells for radiotherapy of Dupuytren's and Ledderhose disease, so the radiation that is designed to kill proliferating fibroblasts in diseased tissue also causes considerable collateral damage in the basal layers of the skin.

If enough proliferating epidermal cells that were destined to repopulate the skin are killed off, a skin reaction may develop and the epidermis may become broken. Basal cell loss is noticeable with doses of about 20–25 Gy, rising beyond that to about 50 Gy. The reaction tends to peak at the end of the week, or up to a week after the end of the treatment. This means that skin reactions are unlikely to be seen with the 2-series, 30 Gy protocol, but may be seen with the 21Gy, ten-day protocol. 

The most common skin reaction is a slight superficial, often patchy, reddening of the skin (erythema). Occasionally the skin becomes dry, flaky or scaly. Rarely, the skin may blister, peel and slough off. Combinations of these three reactions are sometimes seen, and the skin may also become itchy, uncomfortable or even painful.

Most skin reactions disappear within 4 weeks of treatment, though reformed skin may be strongly coloured for some time, as a consequence of radiation damage to the cells that produce melanin. This 4-week recovery period sets a lower limit of the gap between two sequences of treatment in the 30 Gy protocol. Clearly, a longer gap gives more time for the skin to regenerate.

The skin may never completely recover its earlier elasticity or thickness. Furthermore, because the disease is no longer active, previously inflamed areas are likely to become less puffy, making it easier to detect and outline the structures below the skin. Thus, the nodules and cords may become more pronounced both visually and to the touch.

There is no evidence that washing makes skin reactions worse, but there is some evidence that not washing may lead to problems. If your skin is intact, you may swim during and after radiotherapy, but you must rinse your skin well afterwards and moisten it with aqueous cream.

There is no good evidence that aqueous cream is less effective than topical ascorbic acid, creams containing starch, or creams with active ingredients like sucralfate, hyaluronic acid, and aloe vera gel.

The only side effects I have experienced was a slight ache in my palms that felt a little like sunburn, starting about 4 days into the therapy, and then slight redness in the creases in my hands for a few weeks. I think most people probably have a similar minimal reaction, though certainly, some people find that they react much more to the radiation.

You may also be interested in https://www.facebook.com/media/set/...
Wells, M., and MacBride, S. (2003). Radiation skin reactions. In Supportive Care in Radiotherapy, S. Faithfull, and M. Wells, eds. (Elsevier Science Ltd).

Resources: 
http://www.ycn.nhs.uk/html/downloads/ltht-managingradiotherapyinducedskinreactions-oct2011.pdf

https://journals.rcni.com/cancer-nursing-practice/skin-reactions-from-radiotherapy-cnp.13.9.16.e1146

54.  What is the question title here ?

Radiation damages DNA. This damage is likely to be fatal to proliferating cells, while non-proliferating cells, given time, can repair the damage. Early in the development of Dupuytren's and Ledderhose's disease, cells called fibroblasts proliferate and develop the capacity to contract. Radiotherapy uses enough radiation to kill proliferating cells while not permanently damaging normal, non-proliferating cells. It achieves this by ensuring that normal cells have the time they need to recover while proliferating cells do not.

This has an important implication. There's no point in irradiating a hand or foot if the disease isn't active and the fibroblasts aren't replicating. If the disease isn't active, the fibroblasts are no more vulnerable than any other cells. For the radiation to be effective we must time the therapy in relation to the disease's cycle, not as a function of our convenience or that of the clinic. How do you know if the disease is active? For many people, active disease makes the palms itch and tingle. Active disease also manifests as hardening of nodules (Prof Seegenschmiedt compares the hardness of a new nodule to that of a tomato, while as it gets older it is like an orange, then a tennis ball and finally a coconut), the appearance of new nodules, and the appearance or tightening of cords over the previous month or so.
In the protocol developed by Prof Seegenschmiedt and his team, rather than irradiating the hand or foot with, say, 30Gy in a single dose, half the dose is fractionated over 5 days at the rate of 3Gy a day, followed by a gap of 12 to 16 weeks, and then the treatment is completed with another half dose of 15Gy spread over 5 days. 

Why not deliver all the 15Gy in a single dose instead of splitting it over 5 days? Spreading (half of) the total dose over 5 days gives the healthy cells a bit of breathing space each day to repair their damaged DNA, while the proliferating fibroblasts are increasingly damaged and less and less capable of survival as the treatment is repeated day after day. Interrupting the sequence by a weekend almost certainly makes no difference to the effectiveness of the treatment. The two-day break from treatment might help the normal cells recover a bit more, which would perhaps help to reduce any likelihood of acute side effects. The point is to give the first 15Gy in a reasonably short space of time (less than a couple of weeks) to make sure that the proliferating fibroblasts get as damaged as possible without the chance to repair themselves, but over time long enough to give normal cells that chance.

The interval between the two half-treatments, or series of radiation, is probably more important than we yet realise. The purpose of the gap is to allow the normal cells time to recover completely, but more importantly, to allow any fibroblasts that were quiescent at the time of the first radiation to begin their replication. In an ideal world, the second set of treatments wouldn't be necessary - and that's the premise of the single 7-day treatment. But the biological world doesn't behave for our convenience. So, we can be sure that the first set will miss some quiescent fibroblasts. 

How to make sure that they are active during the second set? The current regime for Dupuytren's and Ledderhose disease is based on what oncologists have found to be effective against certain cancers. The art is to destroy as much of the proliferating tissue as possible in the first of the two half-sessions, without damaging the healthy tissue beyond repair, and then wait an appropriate time to ambush the newly proliferating cells a few weeks later. My guess is that Prof Seegenschmiedt has enough experience to have it down - the longer the better, up to about 4 months. A shorter time doesn't catch them waking up, and a long time allows them to get out of phase so some will be quiescent again. About 12 to 16 weeks seems to be the optimum. 

Many oncologists use a shorter break, often of 4 to 6 weeks.
To the best of my belief, our present state of understanding of the histological effect of radiation on Dupuytren's and Ledderhose disease is not great enough to know whether other fractionation regimes are as good as, or better than, the one used by Prof Seegenschmiedt. A very large clinical trial would be needed to give statistical validity to the most effective protocol for most people (everyone is different), but Prof Seegenschmiedt’s protocol seems to give satisfactory results in most cases. 

I told Prof Seegenschmiedt that I had heard that some radiation oncologists treating Dupuytren's disease were using his 30Gy fractionated protocol (5 days, a gap of several weeks, 5 days) but making the second series of 5 optional so that it would only be delivered “if needed”. He looked dismayed and said, “not enough time! Not enough time! You cannot possibly make a diagnosis on the progress in such a short time after the first series. This is not fair to the patient! We know that to stop the progress of the disease we must deliver the highest possible dose compatible with avoiding side effects, and we know that the dose we need is around 30Gy. The gap between the two series of 5 isn’t to give the doctor the opportunity to decide whether to continue. It is to give time for the healthy tissue to recover and for Dupuytren's fibroblasts that were not proliferating at the first treatment the time to start proliferating and become vulnerable to the radiation.”

He was, I think, quite appalled that anyone would regard the second series as anything but part of a coherent single treatment of hyper fractionated radiation. For him, it simply doesn't make sense to stop half-way through, and his data suggest that 15Gy will probably be better than nothing at all, but nothing like as effective as 21Gy, which in turn is not as effective as 30Gy.

I also asked Prof Seegenschmiedt about the “7 vs 10” protocols – that is, the protocol in which 21Gy are delivered in 7 doses, relative to the protocol in which 31Gy are delivered in the “5-gap-5” sequence. 

He said, first, that he would always recommend the 5-gap-5 protocol since it gives rise to better results (he now has better statistics to show this but has not yet written them up) and fewer side-effects. 

Secondly, he said that it was important that the 7-dose protocol should take place over more than 7 days. The most effective schedule is one that takes place over 15 days, with radiation every other day, with a break at the weekends (M-W-F, M-W-F, M). The reason for this is that 21Gy is a lot of radiation for the body to absorb and deal with. If the series is compacted in time, it greatly increases the risk of acute side effects, because the dose is too concentrated. Even when it is delivered over 2+ weeks, acute side effects occur more frequently than they do with the 5-gap-5 protocol.

55.  Can I have RT with a steel pin in my wrist?

Yes, you can. 
Radiation oncologists deal with this issue routinely. A common example is when a patient being treated for prostate cancer has a metal hip replacement.

If you have a metal pin in your wrist or hand, tell your oncologist. They may decide to schedule a CT scan to help plan the therapy. Many practices use this information as input for planning software that tailor-makes the radiation sequence for you.