DUPUYTREN'S
DISEASE:
FREQUENTLY ASKED QUESTIONS
AND LINKS TO PUBLISHED STUDIES: FAQS & FACTS
These pages include answers to frequently asked questions regarding
Dupuytren's disease. There is quite a bit known about Dupuytren's, but
because we don't yet have all of the pieces of the puzzle, the bits
that we do know don't all fit tidily together. There are also a fair
number of undocumented urban legends. This page only includes
information which has been investigated and published in recognized
medical journals - the stuff that doctors read. For verification and
more information, this
page links to source material at the National
Library of
Medicine. Browse around! There's quite a bit here to consider.
-
Why? -
What is it due to? The exact process
is still unknown, despite many bits of information. The body chemistry
is abnormal in the entire region, even in areas not visibly changed by
Dupuytren's 3373152,
6768572,
589933,
9369955,
8501391.
Here are a
few parts of the picture - see if you can figure
out how all of this fits together...
- The balance between certain enzymes
(matrix
metalloproteinases
14504511,
9768907, fibrinolysins 3958550,
plasminogen activators 3693826)
and their natural inhibitors is disturbed in
patients with active Dupuytren's disease, and may be affected by tension
on the affected tissues
9665512.
- The cells in the cords of Dupuytren's
disease are
unusually sensitive to the effects of "growth factors",
normal body
chemicals involved in wound healing. These include
transforming growth factor beta 1 (TGF-beta(1)
12849947,
12729127 ,
8618012, transforming growth
factor beta 2 (TGF-beta(2)
12678125,
8683048, basic fibroblast growth factor (bFGF)
1325742, platelet derived growth factor (PDGF)
12087679,
7822340,
1564283 and others
9120728,
7722248,
8056971,
8320323. The process may be
triggered by a combination of mechanical stress and either TGF-beta
10050239,
or PDGF
8893764 .
- Dupuytren's cords have unusually high levels of
levels of the
protein tyrosine phosphorylated beta-catenin
12802275 , and the cells have higher than normal levels of
the
substance alpha smooth muscle actin
11599921 and the enzyme lysyl oxydase 6130030.
- Cell-matrix interaction
abnormalities, stimulating contraction
9369955,
9065582,
8525780.
A three dimensional mesh of actin microfilaments (the
"fibronexus") links cells to each other and to the extracellular
matrix
1867394, which, in Dupuytren's disease, contains unusually
high levels of fibronectin 3519746,
6386626.
- Abnormal androgen receptors have
been implicated in the
abnormal tissue
11853085 ,
10194020,
1798252, although not by all investigators 3794501.
- Low oxygen levels resulting in
reactive forms of oxygen (superoxide free radicals, oxygen
free
radicals) due to poor circulation have
been implicated
12087679,
10050241,
1769989, possibly due to
activation of the enzyme xanthine oxidase
1695516, 2825907.
The blood clotting system may be triggered by production of high level
of plasminogen activator 6197420.
Microvascular circulatory changes develop,
with
narrowing and blockage of capillaries
1960491,
2322211,
2722922, microscopic hemorrhage 6693745
and other changes in the blood vessel walls 4082789,
6150573.
This might explain the relationship of smoking
to Dupuytren's. Miroculatory changes may
arise from abnormal regulatory nerves in the fascia itself
2472714.
Nodules show near complete absence of blood vessels 6693745,
and other studies show evidence of low oxygen levels in the diseased
tissues 6877040.
- T-cell and B-cell Immune mechanisms
,
9888668,
8099992, autoantibodies to
collagen
8181183, 3485693
or other immune mechanisms
2471021, 3138883,
6353806
may be involved.
- Genetic variations
have been demonstrated in nodules, in the form of recurrent clonal
numerical abnormalities
9973941,
9352799,
3414684.
- The contraction is due to a mechanism also seen in
other contracting tissues such as healing wounds and some types of
cancers 6491814.
Dupuytren's fibroblasts 6507097
can acquire smooth muscle characteristics
and are then able to contract
7642925. These modified
fibroblasts are called myofibroblasts
1960491, and are found in nodules, but not cords
1769990, 6491814,
7071229.
In diffuse disease,
these changes can affect cells in the skin as well as the fascia
8294839.
Myofibroblasts contract through an interaction of myofilaments and the
enzyme ATPase within their cell bodies, and the extent of recurrence after
surgery correlates with myofibroblast activity at the time of surgery 6683733,
2754197.
- Certain nerve endings (Pacinian
corpuscles) are enlarged and surrounded by fibrous tissue in affected
areas 3358315,
2472714.
- Overall collagen metabolism may
be disturbed in patients with Dupuytren's 2883783.
Type III collagen is increased in
Dupuytren's cords 6386626,
6740656.
- Mechanical tension forces or
stretching the affected area may
provoke contracture
14599823,
12866952,
12449347,
10050239,
9763277,
9665511, possibly by stimulating changes in the
microcirculation
8917718. Dynamic physical forces may
produce biochemical changes through changes in tissue
electrical
fields
1284015 . Paradoxically, continuous tension
on the tissues
causes a temporary reversal of the process, probably by stimulating
enzymes involved in tissue remodelling
7964107. One hypothesis is that loss of normal gliding motion
between layers of fascia results in abnormal tissue tension which
provokes the contracture process 7152372.
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