Wednesday, April 2, 2014

Recent Surgical and Medical Advances in the Treatment of Dupuytren’s Disease - A Systematic Review of the Literature

Open Orthop J. 2012; 6: 77–82.

Published online Feb 23, 2012. doi:  10.2174/1874325001206010077
PMCID: PMC3293169
Suppl 1

Recent Surgical and Medical Advances in the Treatment of Dupuytren’s Disease - A Systematic Review of the Literature

Abstract

Dupuytren’s
disease (DD) is a type of fibromatosis which progressively results in
the shortening and thickening of the fibrous tissue of the palmar
fascia. This condition which predominantly affects white-northern
Europeans has been identified since 1614. DD can affect certain
activities of daily living such as face washing, combing hair and
putting hand in a glove. The origin of Dupuytren’s contracture is still
unknown, but there are a number of treatments that doctors have come
across throughout the years. Historically surgery has been the mainstay
treatment for DD but not the only one. The objective is to make a
structured review of the most recent advances in treatment of DD
including the surgical and medical interventions. We have looked at the
most relevant published articles regarding the various treatment options
for DD. This review has taken 55 articles into consideration which have
met the inclusion criteria. The most recent treatments used are
multi-needle aponeurotomy, extensive percutaneous aponeurotomy and
lipografting, injecting collagenase Clostridium histolyticum, INF-gamma
and shockwave therapy as well as radiotherapy. Each of these treatments
has certain advantages and drawbacks and cannot be used for every
patient. In order to prevent this condition, spending more time and
money in the topic is required to reach better and more consistent
treatments and ultimately to eradicate this disease.

Keywords: Dupuytren contracture, dupuytren disease, medical, surgical, treatment, advances.

BACKGROUND INFORMATION

The first doctor who came across this condition was Plater in 1614 [1].
In 1831 a French military surgeon called Guillaume Dupuytren became
famous for describing and operating on palmar fibromatosis, which is now
commonly known as Dupuytren’s disease. The disease is described as a
type of fibromatosis characterized by nodular and/or distributed
aggregates of immature fibroblasts dispersed in a dense collagen [2].
The progressive and irreversible flexion contractures of the phalangeal
joints of the hand are the nature of this disease. These flections
which predominantly affect the small and ring finger are due to the
proliferation of myofibroblasts in the fascia of the hand.
Myofibroblasts were the first responsible cause for contracture in this
disease. It was first due to their ultrastructural identification in
transmission electron-microscopic studies but later on scientists showed
that the contracture was mainly due to the expression of Alpha-smooth
muscle actin (SMA) in cells from tissue explants. Furthermore, it was
shown that myofibroblasts can generate contractile force [3, 4].

EPIDEMIOLOGY

Looking
at the incidence of Dupuytren’s disease (DD), white-northern Europeans
have the highest rate whereas dark-skinned individuals have the lowest
number of occurrences [5, 6]. Twin studies have shown that there is some evidence supporting the theory that this disease could be a familial disorder [7].
It is still uncertain whether Dupuytren’s disease is a monogenic or a
polygenic condition as this condition has variable inheritance patterns
and different levels of gene expression.
Scandinavians
and people with Northern European ancestry were mainly responsible for
the spread of this disease hence it is being called the “Viking disease”
[8].
The theory of Nordic origin of the disease can be supported by the high
incidence rate among the people in Denmark as well as in the northern
part of the UK [9].

Both
age and sex, have an effect on the occurrence of Dupuytren’s disease.
The incidence is very low among teens and people in their twenties but
the risk of having this condition increases each decade. According to
Mikkelsen et al. the onset of Dupuytren’s contracture (DC) is
indirectly proportional to the recurrence and progression of this
disease. In other words the earlier the onset of the disease the more
likely the recurrence and progression of Dupuytren’s contracture in the
future [10, 11]
Men are up to 15 times more likely to suffer from this disease. DC
however, is less sever in women and may even remain unnoticed. During
the 8th and 9th decade of life the ratio between affected men and women is equal [11].
There
is mixed evidence as to what the causes and consequences of Dupuytren’
contracture may be. Scientists agree on a well-established link between
this disease and diabetes mellitus (DM). Patients who develop
Dupuytren’s disease and suffer from DM have more nodules and less
contraction [12].
There is no reliable evidence for other diseases such as liver disease,
TB, syphilis, high serum lipids and HIV+ to be associated with
Dupuytren’s contracture. There is a degree of controversy as to whether
there is an association between epilepsy, smoking and alcohol intake and
Dupuytren’s disease. There are a considerable number of individuals
suffering from this condition who have never smoked or drank alcohol.
Moreover, a direct link between work-related activities such as using
vibrating machines and increasing risk of Dupuytren’s disease has not
been established [13,14].
One statistical finding that should not be underestimated is that 42%
of people with severe DC died of cancer. It is evident that more
investigation is needed to confirm what can be the cause of this disease
and for the time being the patients should be told that the cause of
this condition is unknown [15].

THE DISEASE PROCESS

The
known process of the disease is similar to wound healing which involves
the proliferation of the fibroblasts and deposition of the collagen and
myofibroblast contraction. This process works with the aid of a number
of growth factors such as transforming growth factor Beta [16, 17].
Bands of fascial fibres, which are lining longitudinally in the
subcutaneous tissue of the palm that anchor the skin of the palm grow
thick fibrous cords which result in the contraction of the digits [18].
Scientists have found similarities between the presenting features of
neoplastic process and Dupuytren’s disease. They both include specific
chromosomal defects and high rates of recurrence post surgery [16, 17, 19, 20].
Dupuytren’s
contracture can be related with other fibromatoses such as Peyronie
disease, Ledderhose disease as well as fibromatosis of the dorsum of the
proximal interphalangeal joints known as Garrod’s nodules or knukle
pads. Investigations have shown that these diseases are identical from
the histopathological perspective and patients who suffer from
additional fibromatosis can develop new occurrences of the disease in
different areas post operatively [21].

DD
can be classified into 3 main stages: First stage is the early onset of
the disease where small nodules and lumps appear under the digits of
palmer crease. In stage two the condition becomes more extensive and
involves the fascia and the digits. The final and third stage is the
spread of the disease into the fingers and the creation of strong cords
which result in the flexion of the fingers and loss of normal extension [15].

This
disease remains mainly undetected until there is some flexion deformity
of the digits. In the case of a certain diagnosis, there are two major
criteria for referral and treatment of the patient. 1. If the
contracture is becoming progressively worse on repeated examination and
compared to previous history. 2. When there is a noticeable functional
disability of the hand [15].
Dupuytren’s disease can affect certain activities of daily living.
Among the most significant is face washing in which the eye is being
pocked by the affected digit. Combing hair and putting the hand in a
glove are also ranked as the difficulties that a patient with such a
disease will encounter [15].
Dupuytren’s contracture develops in both hands regardless of hand
dominance. The digits which are predominately affected are the ring
finger and the small finger which are followed by the index, the middle
finger and the thumb. The severity and the impact of the disease is
different for every individual but DD presents more aggressively in the
younger individuals when it occurs [15].

ASSESSMENT OF SUSPECTED DUPUYTREN’S DISEASE

The
diagnosis of Dupuytren’s disease is often made by the general
practitioner. Even though there are a variety of different causes that
lead to hand contracture these do not present with nodules in the palm.
Once the patient is referred to a hand specialist Orthopedic or a
plastic surgeon the assessment initiates with a thorough history taking
that involves gathering the most relevant information such as: Age,
gender, ethnicity, occupation, manual hobbies, hand dominance, family
history of this condition, age of onset, symptoms, disease progression,
previous treatment, medical history of DM and epilepsy, drug history as
well as psychosocial history [15]
With the help of a detailed history one can predict how the disease
will affect the patient’s occupation and by looking at the family
history the post operative reoccurrence rate can be estimated.

The
physical examination commences with the inspection of both hands in
particular the affected hand. Great attention is given to the site of
nodules, skin dimpling on the palm and digits, degree of skin
involvement as well as signs of other types of fibromatoses in the hand.
Furthermore, the patient might have previous scars in the palm in the
case of disease recurrence [15].

One useful test that greatly aids staging Dupuytren’s disease is the Hueston Table Top Test [22].
This is a simple test as the patient needs to put his/her hand prone on
the table. If the hand does not go flat then one can say the Hueston
Table Top Test is positive which indicates that the disease is in an
active or moderate stage. The early stages of the disease are not easy
to identify since Dupuytren’s disease starts asymptomatically. By the
time the patient sees the doctor it is already in its moderate or severe
stage.

MATERIAL AND METHOD

In
this review, the relevant articles were searched primarily from the
electronic data bases AMED, ASSIA (CSA Illumina), CINAHL (EBSCO),
Conference Proceedings Citation Index: Science (ISI) on Web of
Knowledge, EMBASE, Medline, PREMEDLINE In-Process & Non-Indexed
Citations (OvidSP), PsycINFO (OvidSP), PubMed, Science Citation Index
(ISI) on Web of Knowledge, Social Sciences Citation Index (ISI) on Web
of Knowledge and Cochrane Library (Wiley) and ZETOC. The following key
words were used for citing the appropriate articles: Dupuytren’s disease
_ Contracture _ assessment _ referral _ medical treatment _ surgical
treatment _ non-surgical treatment _ radiotherapy.

The
following inclusion criteria were used to select relevant studies: A)
Any type of surgical treatment from the first to the most recent
methods, B) All relevant medical and non surgical treatments, C)
Articles experimenting new methods of treatment on animals for human
applications. Articles which were excluded: A) did not include treatment
for Dupuytren’s disease, B) Articles that were written in a language
other than English. Out of 97 articles and studies that were viewed 55
were found relevant and suited the inclusion criteria. The relevant
information from these articles is summarized in the result section.

RESULT

According
to the genetic analyses, Dupuytren’s disease is an autosomal dominant
disorder with a variable penetrance and gene expression [23].
Therefore, there is no cure for this disease and only very few
treatment options are available for the individuals suffering from this
condition. These treatment options are summarized in Tables 11 and 22.
The most commonly used treatments are surgery, open or percutaneus
needle aponeurotomy, collagenase clostridium histolyticum injections,
corticosteroid injections and radiotherapy [24]
Table 1.
Summarizes the Major Surgical Procedures for Treating DD
Table 2.
Demonstrates Recent Medical Interventions for Treating and Reducing the Recurrence of DD

SURGICAL INTERVENTION

Surgery
is the most commonly used treatment option which is recommended for
functionally impaired patients with contractures more than 30° of the MP
joint [25-27].
There is some degree of disagreement as to when surgery is recommended
when PIP joints are affected. Certain authors would consider any degree
of contracture of PIP joints as an indication for surgery. Others
suggest 15° to 30° of PIP joint to take operation as an option [26,28].
In contrast to these professor McGrouther states that it is better to
“rely on functional difficulty and the rate of progression when deciding
on surgery, rather than choosing a set amount of joint contracture [29].

Open, limited fasciectomy is currently ranked as the most commonly used surgical treatment [30-34]
It is interesting to note that between 2003 and 2008 fasciectomy was
the main surgical method in treatment of Dupuytren’s contracture in
England [35].
In a limited fasciectomy the involved fascia is removed and in cases
where the disease is not very extensive fasciotomy of the affected
fascia is performed [15].
Even if surgery is the treatment of choice it does not mean that there
are no complications associated with it. Among the most significant
postoperative complications are haematoma, injuries to nerves, vascular
injury, skin necrosis, oedema, reflex sympathetic dystrophy and
amputation of the finger which is rare. The most common complication
that patients encounter post operatively is joint stiffness and reduced
flexion ability compared to their pre-operative state [29].

There
are two types of fasciotomies, open and closed fasciotomies. Open
fasciotomy is the classic fasciotomy where the surgeon uses a scalpel to
section the cords [36].
The closed technique or percutaneous needle aponeurotomy involves a
minimally invasive operation with a very low complication rate and good
short-term results in mild or moderate contractures [37-41]
In this technique a small needle is used to weaken and manipulate the
cords. The targeted cords will eventually snap very easily after being
weakened, by simply extending the fingers passively. The post operative
results are predominantly satisfactory but extensive hand therapy such
as using night splints and regular physiotherapy exercises are required
for better outcomes [42]. Despite its advantages studies have shown that percutaneous needle aponeurotomy has a high recurrence rate [42].

When
treating a patient with Dupuytren’s disease, surgery has the best
outcome but not all individuals with digital contractures will benefit
from it [29].
By way of illustration, open fasciotomy is not performed on elderly
patients, those with co-morbidities or both. For these individuals
closed fasciotomy or percutaneous needle fasciotomy can prove helpful
even though the chance of developing this disease is very high.

Dermofasciectomy
is the preferred procedure for the patients with advanced Dupuytren’s
disease or patients with high recurrence. In this technique the skin and
the affected fascia are both removed and the wound is grafted [21].
A further surgical treatment for this condition is the Jacobsen flap,
which was first described by Jacobsen and Nielsen. This is a
modification of McCash’s technique which was first performed in 1964 [43]. This modification allows the surgeon to expose the disease in both the palm and the fingers using only two linear incisions [44].
There are many advantages when choosing this type of surgery, for
instance reducing the risk of developing haematoma as well as oedema.
Furthermore, there is no need for skin grafting and causing additional
scars on the donor site. The patient will be able to mobilize the hand
immediately after the operation which reduces the risks of developing
oedema. Due to the fact that the wound is left open, the patient has to
wear a dynamic orthoplast splint for approximately 10 weeks in addition
to physical therapy. The wound can easily become infected and thus needs
to be checked and looked after very carefully particularly in patients
who are suffering from diabetes mellitus and other metabolic disorders.
Skin necrosis as well as progressive flexion deformity in the distal
interphalangeal joint as a result of shrinking of the skin should also
not be underestimated when considering this procedure [45]. Table 11 will summarize some popular surgical procedures and their outcomes towards treating DD.

MEDICAL INTERVENTIONS

Since
Dupuytren’s contracture became known to scientists and medical
professionals numerous ways of treating this disease have been
investigated and different alternatives to surgery have been found. The
most effective non surgical treatment which has also recently got
approved by Food and Drug Administration (FDA) is injectable collagenase
clostridium histolyticum which is known as Xiaflex. Collagenase
clostridium histolyticum is an enzyme that dissolves collagen and thus
it is injected directly into the cord. One day post Xiaflex injection
the enzyme has had adequate time to dissolve certain part of the
collagen and this makes it easier for the doctor to straighten the
finger manually. Often more than one injection is necessary to give the
finger its previous healthy condition back. If more than one digit is
affected then several injections spread over months are required. On the
grounds that injecting collagenase clostridium histolyticum is a very
new treatment its long-term safety and recurrence rate requires further
assessment [46].

Tomasek et al.,
have investigated the effect of INF-gamma on myofibroblast and came to
the conclusion that INF-gamma is able to suppress the differentiation of
myofibroblasts and thus the contractile force is being reduced as well.
Therefore, it has the potential to be used as a non surgical treatment
for this condition [2]. According to Trojian et al.,
using steroid injections into the Dupuytren nodule in the early stages
of the disease can prevent its progression and the need of fasciectomy.
Further research and investigation is needed to confirm this hypothesis.

Another non invasive tool that can be used for treatment of Dupuytren’s disease is shock wave therapy. Knobloch et al.,
have primarily done a randomized-controlled trial in Peyronie’s disease
using focused extracorporeal shock waves which reduced the pain and
dramatically improved the erectile function and the quality of life. As
Peyronie’s disease resembles Dupuytren’s to a large extent the same
method was used in a randomized-controlled trail on individuals with
Dupuytren’s contracture. The hypothesis is that focused extracorporeal
shock wav
e therapy can be use as a non-invasive tool to decrease the
force of contracture and reduce the fibromatosis of the palm [47]. It is commonly alleged that antiepileptic drugs such as Phenobarbital are risk factors for developing Dupuytren’s disease [48]. Tripoli et al.,
studied a group of patients on Phenobarbital and some who were on
benzodiazepine and managed to find out that the administration of
benzodiazepine reduces the risk of recurrence of this condition [48].
Studies have also shown that radiotherapy can play an important role on
preventing the progression of the disease when applied in the
early-stages of Dupuytren’s contracture [49]. The most recent medical interventions for DD are demonstrated in Table 22.

DISCUSSION

The
first ever treatment of Dupuytren’s contracture was surgery which was
performed by Guillaume Dupuytren and for many years doctors followed his
way of dealing with the disease. Today, there are numerous ways of
dealing with this condition and doctors can choose the most suitable
method of treatment for their patients. Each technique has its own
advantages and disadvantages. Certain surgical procedures have a very
low recurrence rate such as dermofasciectomy [50] or Jacobsen flap [55]
with a high risk of post-operative complication rates when compared to
percutaneus needle aponeurotomy which has a low complication rate but a
high rate of disease recurrence. There is a similar picture when looking
at the non-surgical treatments, by way of illustration Injectable
collagenase Clostridium histolyticum is an effective and immediate
medical treatment but it is an expensive injection to get hold of, thus
in certain countries where the insurance does not cover the costs
patients might not be able to afford this treatment. Having mentioned
that, recent statistics show that 3-5% of the UK population is suffering
from Dupuytren’s disease and the National Health Service has to provide
the most cost-effective treatments for the patients [35].
At the moment Fasciectomy and fasciotomy are the main treatments for
Dupuytren’s contracture in the UK. The estimated costs for treatment of
DD in year 2010-2011 were £41,576,141. In this year the costs per
patient ranged from £2,736 for a day-case Fasciectomy to £9,210 for a
day-case Revision Digital [35].

Getting
away from the financial side of medicine, it is essential to find the
main cause of Dupuytren’s contracture in order to prevent the spread of
this disease. One way could be to invest more time in the genetic links
of this condition and to explore the similarities between people
suffering from this disease. It would also be beneficial to find out the
cause of death of these patients as they might die from similar
conditions. One study has shown that 42% of the patients with severe DD
died of cancer; therefore it is worth considering whether people having
DC are more likely to develop neoplastic conditions.
Using
screening programs would help to identify individuals with high risk of
developing DD and take immediate measures to prevent them from
developing this condition. However the risk of recurrence might still be
the same, unless the origin of this disease becomes known to us.

CONCLUSION

Dupuytren’s
Disease is a type of fibromatoses characterized by nodular and
distributed aggregates of immature fibroblasts dispersed in a dense
collagen with no known origin. The new advances in the treatment of this
disease are the modified and improved versions of the previous
treatments with lower complication rates. Among the most recent are
Multi-needle aponeurotomy, Extensive percutaneous aponeurotomy and
lipografting, injecting collagenase Clostridium histolyticum, INF-gamma
and shockwave therapy as well as Radiotherapy. Each of these treatments
has certain advantages and drawbacks and cannot be used for every
patient, and depending on the stage of the disease the treatment might
alter. In order to prevent this condition spending more time and money
in the topic is required to reach better and more consistent treatments
and ultimately eradicate this disease.

ACKNOWLEDGEMENT

None declared.

CONFLICT OF INTEREST

None declared.

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