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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44. Jacobsen K, Holst-Nielsen F. A modified McCash operation for
Dupuytren's contracture. Scand J Plast Reconstr Surg. 1977;11(3
):231–3.
[PubMed]
45. Tripoli M, Merle M. The "Jacobsen Flap" for the treatment of
stages III-IV Dupuytren's disease: a review of 98 cases. J Hand
Surg Eur.
2008;33(6
):779–82.
[PubMed]
46. Gilpin D, Coleman S, Hall S, Houston A, Karrasch J, Jones N.
Injectable collagenase Clostridium histolyticum: a new nonsurgical
treatment for Dupuytren's disease. J Hand Surg Am. 2010;35(12
):2027–38.
[PubMed]
47. Knobloch K, Kuehn M, Vogt PM. Focused extracorporeal
shockwave therapy in Dupuytren's disease--a hypothesis. Med
Hypothese.
201;76(5
):635–7.
[PubMed]
48. Tripoli M, Cordova A, Moschella F. Dupuytren's contracture as
result of prolonged administration of phenobarbital. Eur Rev Med
Pharmacol Sci.
2011;15(3
):299–302.
[PubMed]
49. Keilholz L, Seegenschmiedt MH, Sauer R. Radiotherapy for
prevention of disease progression in early-stage Dupuytren's
contracture: initial and long-term results. Int J Radiat Oncol Biol
Phys.
1996;36(4
):891–7.
[PubMed]
50. Lubahn JD. Open-palm technique and soft-tissue coverage in
Dupuytren's disease. Hand Clin . 999 ;15(1
):127–36.
[PubMed]
51. Beaudreuil J, Lermusiaux JL, Teyssedou JP, et al. Multi-needle
aponeurotomy for advanced Dupuytren's disease Preliminary
results of safety and efficacy (MNA 1 Study) Joint Bone Spine
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2011;78(6
):625–8.
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52. Hovius SE, Kan HJ, Smit X, Selles RW, Cardoso E, Khouri RK.
Extensive percutaneous aponeurotomy and lipografting a new
treatment for Dupuytren disease. Plast Reconstr Surg. 2011;128(1
):221–8.
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53. Ketchum LD, Donahue TK. The injection of nodules of
Dupuytren's disease with triamcinolone acetonide. J Hand Surg Am
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2000;25(6
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54. Keilholz L, Seegenschmiedt MH, Born AD, Sauer R.
[Radiotherapy in the early stage of Dupuytren's disease. The
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55. Tripoli M, Cordova A, Moschella F. The Jacobsen flap
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Treating Dupuytren's - Acoustic Shockwave Therapy

Treating Dupuytren's

In many cases no treatment is necessary if the condition lies dormant, causes no problems and and does not progress.
Surgery to straighten bent fingers has long been the
established method of treatment, but in recent years new treatments have
become available to deal with the earlier stages of the disease. Some
of these treatments, such as Radiotherapy and Collagenase injections
might not yet be available on the NHS, but all are available from
private clinics in the UK.
You can view an image of our treatment comparison table or download a PDF of our patient leaflet.

 

Recommended Treatments

Stage N, N1 - nodules and cords, slight or no contracture

Radiotherapy - shows promising results of halting or
slowing any progression of the disease, but has minor side-effects, such
as dry skin and is not always effective. It is only effective during
the active or proliferation phase when nodules are growing and cords may
be developing. This is often accompanied by symptoms of soreness,
tingling, aches, and so on.
If there are no signs of activity then you
should wait and see, but examine and possibly photograph your hands
regularly for signs of changes.
Corticosterod injections - such as Triamcinolone have been used with some success by some Doctors.

 

Stage 1 and 2 - slight to moderate contracture

Needle Aponeurotomy - is a good option if any
contracture is not too severe and if the cord is well away from tendons
and nerves in the hand.
Collagenase injection ( Xiapex) - Has good
results for contracture but carries a small risk of tendon rupture. It
works by dissolving the strands of tissue in the cords or strings. Some
patients need may a second injection. In most cases the contracture is
straightened by the Doctor the following day or a few days after the
injection.

 

Stage 3 and 4 - severe contracture

Surgery - there are different types and your
your surgeon will decide which is needed. Surgery is advised when the
MCP joint (the one that connects the finger to the hand) is more than
40% bent, or the PIP joint (second finger joint from the tip) is more
than 20% bent.

 

Other treatments (not in general clinical use)

Tamoxifen - (Acts as Growth hormone beta inhibitor)
not used because of potential serious side effects such as stroke-risk.
More promising is the idea of converting the presentation to a gel or
ointment for local application.
Cortisone - (steroid) injection into the nodule
or cord. This lessens pain and inflammation (in theory). Temporary
benefits only for most patients but some have seen a lasting reduction
in nodules.
Cryosurgery-
the application of extreme cold to the tissues. The nodule has to be
big enough (1 cm) to place the probe in it. It freezes the cells and
thus shrinks theb nodule, and it freezes the nerve ending around the
nodule and reduces the pain.
Verapamil - A calcium channel
blocker, applied as a gel. Reported as effective in some cases but the
cost is prohibitive. Not available on the NHS as far as we know.
Penetration of Verapamil into the affected tissues has not been proven
so the effect of the drug applied this way is questionable.
5 fluoro-uracil - injected into the wound area after surgery can limit scarring.
Acetyl -L - Carnitine - This is an essential
amino acid, taken as tablets is reported to have good effect in some
Peyronie’s cases.
Allopurinol - Xanthine oxidase inhibitor used
as gout medicine. Hypoxanthine is found in high concentrations in
Dupuytren’s tissue, and allopurinol can reduce this, thus reducing the
amount of free radicals in the tissues. However clinical results are not
very promising, and some suggest the people who benefited did so
because their gout improved, not their Dupuytren’s.
Ultrasound - The idea is that it can break the
disulfide bonds in the cords, and produces heat to increase the oxygen
and bloodflow. Not proven very successful but some patients can have
reduction aof pain and increased movement after treatment.
Hyperbaric Chamber - As the etiology of the
nodules suggests tissue damage by hypoxia (lack of oxygen) this has been
tried. One report of patient improvement.
Vitamin E ointment - Does not appear to be very successful. The idea is to ‘mop up free radicals’.
Interferon - injected into the nodule or cord. Not proven successful.
Extracorporeal Shockwave Therapy (ESWT) - a non
invasive drug free treatment that takes about 5 minutes. Sudden brusts
of sound are directed into the palm and fingers to loosen the tightening
cords. The vital characteristic of a sockwave is that from zero
decibels to high must happen in a few nanoseconds. The fast moving sound
wave hits the tightened cord and stretches it. Moreover it also
activates stem cells to migrate to the site because through the nerves
the brain has detected a problem and instructs white blood cells to make
a repair. the patient will feel the treatment as uncomfortable, maybe
even painful, but giving a (local) anaesthetic would prevent this repair
process from setting in. The treatment may need to be repeated after
two weeks. Improvements can take place for up to a year after treatment
due to the response of cells to repair the tissues. In over 40 years of
use ( also forproblems such as idneys stones) no side effects have been
encountered.
Verapamil-
gel or injections, reduces the production of collagen and increases the
bodies own enzyme activity to break down collagen strands.


Recent developments:

Botox injection : apart from an enzyme to smooth out wrinkles Botox
also contains another enzyme, that is capable of  reducing contractions,
adhesions and  fibrosis, after surgery.


Halozyme: an injection  ( recombinant hyaloronidase) presently
in use for dissolving blood clots in thrombosis patients ( so already
been tested for safety), it is being trailed for cellulite but could
potentially help Dupuytren's patients in a way similar to Collagenase,
as it degrades collagen.


Alteplase  injections- a compound that stimulates cells in the nodules
and cords to produce their own collagenase. So far it has been tried on
a few Dupuytren's and Lederhose patients who were happy about the
results, but the patent for the drug is pending, so it is a long way
from being widely available, if it ever gets so far.

Cellulite and Focused Extracorporeal Shockwave Therapy for Non-Invasive Body Contouring: a Randomized Trial

Dermatol Ther (Heidelb). Dec 2013; 3(2): 143–155.

Published online Dec 3, 2013. doi:  10.1007/s13555-013-0039-5
PMCID: PMC3889306

Cellulite and Focused Extracorporeal Shockwave Therapy for Non-Invasive Body Contouring: a Randomized Trial

Abstract

Introduction

Focused
extracorporeal shockwave therapy (ESWT) has been demonstrated to
improve wound healing and skin regeneration such as in burn wounds and
scars. We hypothesized that the combination of focused ESWT and a daily
gluteal muscle strength program is superior to SHAM-ESWT and gluteal
muscle strength training in moderate to severe cellulite.

Methods

This
was a single-center, double-blinded, randomized-controlled trial. For
allocation of participants, a 1:1 ratio randomization was performed
using opaque envelopes for the concealment of allocation. Eligible
patients were females aged 18–65 years with cellulite. The primary
outcome parameter was the photo-numeric Cellulite Severity Scale (CSS)
determined by two blinded, independent assessors. The intervention group
(group A) received six sessions of focused ESWT (2,000 impulses,
0.35 mJ/mm2, every 1–2 weeks) at both gluteal and thigh
regions plus specific gluteal strength exercise training. The control
group (group B) received six sessions of SHAM-ESWT plus specific gluteal
strength exercise training.

Results

The CSS in group A was 10.9 ± 3.8 (mean ± SE) before intervention and 8.3 ± 4.1 after 12 weeks (P = 0.001,
2.53 improvement, 95% confidence interval (CI) 1.43–3.62). The CSS in
group B was 10.0 ± 3.8 before intervention and 10.1 ± 3.8 after 12 weeks
(P = 0.876, 95% CI 1.1–0.97). The change of the CSS in group A versus group B was significantly different (P = 0.001, −24.3 effect size, 95% CI −36.5 to −12.1).

Conclusion

The combination of non-invasive, focused ESWT (0.35 mJ/mm2,
2,000 impulses, 6 sessions) in combination with gluteal strength
training was superior to gluteal strength training and SHAM-ESWT in
moderate to severe cellulite in terms of the CSS in a 3-month
perspective. Long-term results have to be evaluated in terms of the
sustainability of these effects.

Electronic supplementary material

The
online version of this article (doi:10.1007/s13555-013-0039-5) contains
supplementary material, which is available to authorized users.
Keywords: Aesthetics, Body contouring, Cellulite, Dermatology, Extracorporeal shock wave therapy, Strength training

Introduction

Cellulite is a widespread problem involving the buttocks and thighs of the female-specific anatomy [1].
The higher number of fat cells stored in female fatty tissue in
contrast to males, the gender-specific dimorphism with subdermal septae
orientated orthogonally toward the skin, and the aging process of
connective tissue lead to an imbalance between lipogenesis and lipolysis
with subsequent large fat cells bulging the skin [1].
Recently, a case–control study in 15 lean women suffering from
cellulite, and age- and body mass index (BMI)-matched controls
identified significantly reduced adiponectin expression using reverse
transcription polymerase chain reaction among the cellulite-affected
patients [2].
Cellulite appears to potentially impair quality of life of affected
females substantially. It appears that younger females affected by
cellulite suffer more in terms of impaired quality of life than more
mature females [3].
Non-randomized
clinical data suggest that extracorporeal shock wave therapy (ESWT) is
beneficial in terms of improved skin elasticity and revitalizing dermis
in females with cellulite [4, 5].
Potentially, a direct effect on the associated lymphedema is a further
potential consequence of ESWT application in cellulite. A recent Korean
prospective clinical trial evaluated the effect of four ESWT sessions
(0.056–0.068 mJ/mm2, 2,000 impulses, ESWT device from Dornier AB2) within 2 weeks in patients suffering from secondary lymphedema [6].
Both the circumference and the thickness of the skin fold of the
affected region were significantly reduced by as much as 37% in line
with a pain reduction on the visual analogue scale [6]. In systemic sclerosis, ESWT is able to again improve pain and the Rodnan skin score for skin wellness [7].
To date, a limited number of non-controlled studies (two Level III [4, 8] and two Level IV studies [9, 10]) examined the effect of ESWT on cellulite with various outcome measures (Table 1).
Table 1
Evidence
levels of currently published clinical trials on the effect of
extracorporeal shock wave therapy (ESWT) on cellulite with different
outcome measures applied
Recently, a small size (n = 25) randomized-controlled trial (RCT) with large confidence intervals (CIs) has been published (level 2 evidence) [11]. The trial involved six sessions over 4 weeks using the STORZ D-ACTOR® 200 by Storz Medical (Tägerwilen, Switzerland) improved depressions, elevations, roughness, and elasticity within 3 months.
Beyond the aforementioned RCT [11],
with small sample size and large confidence intervals, we do not have
any high-level 1b evidence to support the use of focused ESWT for
non-invasive body contouring in cellulite. In addition, we do not know
whether or not and if, to what extent the validated photo-numeric
Cellulite Severity Scale (CSS) is changed by six sessions of focused
ESWT. Currently, we do not have any high-level 1b evidence regarding the
effect of gluteal home-based strength training with or without focused
ESWT on the clinical outcome in cellulite in terms of digital images,
microcirculation and patient self-reported assessment. Given these facts
we sought to overcome these issues and performed a double-blinded, RCT
providing level 1b evidence on the use of focused ESWT in addition to
daily gluteal strength training in various degrees of cellulite. We
hypothesized that the combination of ESWT and a daily gluteal muscle
strength program is superior to SHAM-ESWT and a gluteal muscle strength
program in cellulite.

Methods

The study protocol was composed according to the most recent CONSORT 2010 recommendations for transparent reporting of RCTs [12, 13]. The study protocol according to the CONSORT recommendations has been published previously [14].

Ethics and Trial Registration

This
RCT was approved in May 22, 2009 by the ethics institutional review
board at Hannover Medical School, Germany, under the German title
“Stosswellentherapie und Krafttraining zur Therapie der Cellulite—eine
randomsiert-kontrollierte Studie” (Nr. 5206). The study is
internationally registered at ClinicalTrials.gov with ClinicalTrials.gov
identifier: NCT00947414.
All
procedures followed were in accordance with the ethical standards of the
responsible committee on human experimentation (institutional and
national) and with the Helsinki Declaration of 1975, as revised in 2000
and 2008. Informed consent was obtained from all patients for being
included in the study and for the publication of patient photographs.

Study Design

This was a single-center, double-blinded, RCT with a 1:1 parallel group randomization.

Participants

The
mean age of the enrolled participants was 41.4 years in the
intervention group and 45.0 years in the control group. BMI (mean ± SE)
was 24.2 ± 3.2 kg/m2 in the intervention group and 25.3 ± 4.5 kg/m2 in the control group.
Eligible
patients were females aged between 18 and 65 years with documented
cellulite 0° to 3° according to the Nürnberger Müller score [1].
Exclusion criteria were the following: suspected or evident pregnancy,
no cellulite, no informed consent, and age under 18 years or above
65 years. Patients were recruited by advertisements in local regional
newspapers and via the Internet. The patient enrollment flow chart
according to the CONSORT statement is outlined in Fig. 1.
Fig. 1
CONSORT patient flow chart. Modified with permission from Knobloch et al. [14]

Interventions

In CelluShock-2009 patients were randomly assigned with a 1:1 ratio to either ESWT with 0.35 mJ/mm2 in the intervention group or 0.01 mJ/mm2 in the SHAM-ESWT group. Both groups additionally participated in a home-based, daily gluteal thigh exercise program.
The intervention group received six sessions of ESWT (every 1–2 weeks) with focused shock waves (2,000 impulses, 0.35 mJ/mm2, Fig. 2) plus home-based, daily gluteal strength exercises (Figs. 3, ,4).4). The control group received six sessions of SHAM-ESWT (2,000 impulses, 0.01 mJ/mm2,
every 1–2 weeks) plus home-based, daily gluteal strength exercises.
Extracorporeal shock wave therapy was applied using a STORZ focused
Duolith machine (Taegerwilen, Suisse) as acoustic wave treatment.
Fig. 2
Placement of the shockwave probe from distal to proximal on both thighs
Fig. 3
First exercise (15 repetitions per leg twice a day over 12 weeks)
Fig. 4
Second exercise (15 repetitions per leg twice a day over 12 weeks)
In
order to increase the motivation of the participating females,
especially in terms of follow-up, we added a daily, home-based gluteal
strength exercise program. Twice a day (in the morning and the evening),
two different exercises focusing on the gluteal muscles involving the
piriformis, the gemelli, and the gluteal muscles were performed with 15
repetitions for each leg (Figs. 1, ,2).2).
The compliance to the daily gluteal workout program was noted in a
exercise log to improve and supervise participants’ compliance,
respectively.

Primary and Secondary Outcome Measures

The
primary endpoint, with respect to efficacy of the combined ESWT and
gluteal strength exercises versus SHAM-ESWT and the same gluteal
strength exercise program, was the change on digital photographs
3 months after the last ESWT treatment assessed by the validated CSS [15].
This provided reliable, comprehensive, and reproducible results.
Cellulite severity may be classified according to the result of this
assessment in the CSS in three degrees, as described in Table 2.
Table 2
Cellulite Severity Scale of mild, moderate or severe degree
The
classification was performed based on standardized photographs taken by
a professional medical photographer at baseline and 12 weeks after the
last ESWT treatment in both groups. The assessment of the anonymous
digital images was carried out by two blinded assessors who were not
aware of either the study arm or the fact that it is a baseline or a
follow-up photograph taken 12 weeks after the last ESWT treatment in
both groups.
In order to overcome the problems of
interpretation associated with multiplicity of analyses we decided to
choose the aforementioned clinical endpoint which is a visual one as the
primary endpoint and results as secondary endpoints in CelluShock.
Secondary
endpoints of the CelluShock RCT were as follows: change of
circumference of the thigh (cm), skin elasticity using the Cutometer® (Cutometer MPA 580, Kosmetik Konzept KOKO GmbH & Co KG, Leichlingen, Germany) [1619], and self-assessment of the success on a visual analogue scale 0–10 (0 = no change, 10 = fully satisfied).
All patients were measured at baseline and after 12 weeks regarding the primary and all secondary endpoints.

Power Calculation

To
detect at least a change of two points in the CSS of cellulite, with a
two-sided, 5% significance with an 80% power, a sample size of 26
participants with an estimated drop-out rate of 15% was calculated. This
was done prior to the start of trial.

Randomization and Allocation Sequence

For
allocation of participants, a 1:1 ratio randomization was performed
using opaque envelopes for the concealment of allocation. The allocation
sequence was concealed from the researcher (BJ) enrolling and assessing
participants in sequentially numbered, opaque, sealed envelopes [20].

Blinding

Blinding
was achieved for all participants enrolled in the trial, the
photographer taking the digital images for the primary outcome measure,
the two assessors of the outcome measures, all additional health care
providers, and for the analyst from the biometrical department. Only one
researcher (BJ) was aware of the group assignment performing the
randomization and the ESWT.
The
assessment of the primary and secondary outcomes was performed by
blinded assessors independently from each other, unaware whether the
digital image displayed was before or after therapy or with group
(intervention or control group) was randomized.

Statistical Analysis

The
primary endpoint was change of CSS assessed on digital, standardized
photographs by two independent expert examiners. Student’s t test was applied for parametric data, the Wilcoxon test for non-parametric data, and a level of P < 0.05
was reported as significant. An intention-to-treat analysis was
applied. SPSS (IBM Corp., New York, USA) was used to carry out the
analysis.

CONSORT Flow Chart

Figure 1 highlights the patient flow throughout the CelluShock-2009 RCT (Fig. 1).

Results

Primary Outcome Measure—Cellulite Severity Scale

The
CSS (mean ± SE) in the intervention group was 10.9 ± 3.8 before and
8.3 ± 4.1 after the combined ESWT and strength exercise intervention (P = 0.001, 2.53 improvement (+24%), 95% CI 1.43–3.62) (Figs. 5, ,6,6, ,7,7, ,8,8, ,9,9, ,10;10; Table 3). The CSS in the control group was 10.0 ± 3.8 before and 10.1 ± 3.8 after the SHAM-ESWT and strength exercise intervention (P = 0.876,
95% CI −1.1 to 0.97). The change of the CSS in the intervention group
versus the control group was significantly different (P = 0.001, −24.3 effect size, 95% −36.5 to −12.1).
Fig. 5
Improvement
of the Cellulite Severity Score from 15 to 7 in a female patient
suffering from cellulite before and 3 months after six sessions of
focused extracorporeal shockwave therapy (0.35 mJ/mm2)
Fig. 6
Improvement
of the Cellulite Severity Score from 12 to 2 in a female patient
suffering from cellulite before and 3 months after six sessions of
focused extracorporeal shockwave therapy (0.35 mJ/mm2)
Fig. 7
Improvement
of the Cellulite Severity Score from 10 to 6 in a female patient
suffering from cellulite before and 3 months after six sessions of
focused extracorporeal shockwave therapy (0.35 mJ/mm2)
Fig. 8
No
significant improvement of the Cellulite Severity Score from 13 to 11
in a female patient suffering from cellulite before and 3 months after
six sessions of sham extracorporeal shockwave therapy (0.01 mJ/mm2, control group)
Fig. 9
No
improvement of the Cellulite Severity Score from 4 to 5 in a female
patient suffering from cellulite before and 3 months after six sessions
of sham extracorporeal shockwave therapy (0.01 mJ/mm2, control group)
Fig. 10
Change
of the Cellulite Severity Score before and 3 months after six sessions
of either focused extracorporeal shockwave therapy (ESWT) (0.35 mJ/mm2, intervention group) or SHAM-ESWT (0.01 mJ/mm2, control group)
Table 3
Number
of patients in each group according to the Cellulite Severity Scale in
the intervention and the control group prior and after the intervention
The
results for the five items of the CSS, the cutometer data, and the
thigh circumferences are reported below; all values are given as
mean ± SE unless otherwise stated.

Number of Depressions

The number of depressions in the intervention group was 2.2 ± 0.8 at baseline and 1.8 ± 0.9 at follow-up (P = 0.001,
improvement 0.41, 95% CI 0.17–0.65). The number of depressions in the
control group was 2.0 ± 0.8 at baseline and 2.0 ± 0.7 at follow-up (P = 0.534,
95% CI −0.30 to 0.16). The change of the number of depressions in the
intervention versus the control group was significantly different (P = 0.012, −20.0 effect size, 95% CI −34.8 to −4.4).

Depth of Depressions

The depth of depressions in the intervention group was 2.2 ± 0.8 at baseline and 1.6 ± 0.8 at follow-up (P = 0.001,
0.61 improvement, 95% CI 0.39–0.84). The depth of depressions in the
control group was 2.0 ± 0.8 at baseline and 2.0 ± 0.7 at follow-up (P = 1.0,
95% CI −0.24 to 0.24). The change of the depth of depressions in the
intervention group versus the control group was significantly different (P = 0.001, −31.3 effect size, 95% CI −46.0 to −16.6).

Morphological Appearance of Skin Surface Alterations

The
morphological appearance of skin surface alterations in the
intervention group was 2.2 ± 0.8 at baseline and 1.6 ± 0.8 at follow-up (P = 0.001,
0.6 improvement, 95% 0.36–0.8). The morphological appearance of skin
surface alterations in the control group was 1.9 ± 0.8 at baseline and
1.9 ± 0.6 at follow-up (P = 0.837, 95% CI −0.20 to 0.25). The
change of the morphological appearance of skin surface alterations in
the intervention group versus the control group was significantly
different (P = 0.007, −16.6 effect size, 95% CI −28.7 to −4.6).

Grade of Laxity, Flaccidity or Sagging Skin

The grade of laxity, flaccidity or sagging skin in the intervention group was 2.2 ± 0.8 at baseline and 1.6 ± 0.8 at follow-up (P = 0.001,
0.5 improvement, 95% CI 0.27–0.73). The grade of laxity, flaccidity or
sagging skin in the control group was 2.0 ± 0.9 at baseline and
2.1 ± 0.8 at follow-up (P = 0.516, 95% CI −0.34 to 0.17). The
change of the grade of laxity, flaccidity or sagging skin in the
intervention group versus the control group was significantly different (P = 0.001, −25.1 effect size, 95% CI −39.6 to −10.6).

Classification Scale by Nürnberger and Müller

The
classification scale by Nürnberger and Müller in the intervention group
was 2.2 ± 0.8 at baseline and 1.8 ± 0.9 at follow-up (P = 0.001,
0.5 improvement, 95% CI 0.3–0.8). The classification scale by
Nürnberger and Müller in the control group was 2.1 ± 0.8 at baseline and
2.1 ± 0.7 at follow-up (P = 1.0, 95% CI −0.22 to 0.22). The
change of the classification scale by Nürnberger and Müller in the
intervention group versus the control group was significantly different (P = 0.043, −24.4 effect size, 95% CI −37.7 to −11.1).

Change of Circumference of the Thigh and Body Mass Index

The change of thigh circumference in the intervention group was 61.5 ± 6.2 cm at baseline to 61.0 ± 5.9 cm at follow-up (P = 0.760,
95% CI −2.91 to 3.97). There was no change of thigh circumference in
the control group (61.6 ± 6.9 cm) at baseline versus follow-up
(61.6 ± 6.9 cm; P = 0.996; 95% CI −4.28 to 4.31). Pre- and
post-treatment body weight index did not change in either group
significantly beyond 3%.

Skin Elasticity Using the Cutometer®

The skin elasticity in the intervention group was 14.1 ± 2.5% at baseline and 14.1% ± 1.6 at follow-up (P = 0.963; 95% CI −1.22 to 1.16).
The skin elasticity in the control group was 14.4% ± 1.8 at baseline and 14.1% ± 1.9 at follow-up (P = 0.676; 95% CI −0.91 to 1.38).

Discussion

The combination of focused ESWT (0.35 mJ/mm2,
2,000 impulses, 6 sessions) in combination with gluteal strength
training was superior to a gluteal strength training alone in terms of
the CSS in a 3-month perspective. The significant mean improvement was
24% in the intervention group in contrast to the control group, a
clinically meaningful difference. Second, the SHAM-ESWT and the gluteal
strength training were not able to change the CSS.
The
strengths of this double-blinded, randomized clinical trial are the
independent assessment by two expert examiners who were blinded to both
the patients and the group allocation. Both experts assessed the
digitalized standardized photographs independently and the mean of both
assessments was applied. Second, this is the first registered,
double-blinded, randomized clinical trial to assess the effects of a
gluteal strength training and the combination with focused ESWT. Third,
standardized photographs were taken by a clinical photographer
independently from the study team. Fourth, the control group received
SHAM-ESWT (0.01 mJ/mm2, 2,000 impulses, 6 sessions) which did
not appear to have any clinical effect in terms of the CSS at all, with
identical values before and after the intervention.
However,
to date we cannot estimate the long-term efficacy and sustainability of
the aforementioned clinical effects in a perspective of one or more
years. It is possible that, after a year, an additional treatment might
be warranted, such as a touch-up procedure. In our personal experience,
select cases might benefit even longer than 1 year from a set of six
focused shockwave sessions, but this is only a non-controlled
observation.
The results of this randomized clinical
study should be discussed in detail. The CSS is a validated
photo-numeric Cellulite Severity Scale, which has been published in 2009
by Dr. Hexsel and coworkers [15].
Beyond the well-known Nürnberger and Müller score ranging from 0° to
3°, this validated score appears to better reflect even modest to small
changes of a given therapeutic intervention. The CSS has a high
intraclass correlation coefficient of 0.9 or more and ranges from 1 to
15. Three clinical cellulite severity grades have been proposed by
Hexsel et al. [15] (Table 2).
Given our patients, we included the majority of patients with moderate
to severe degrees of cellulite. This is partially reflected by the mean
age beyond 40 years and the BMI beyond 24.2 kg/m2 in both groups.
As
far as the underlying mechanisms of the evident improvements in the CSS
are concerned, a “mechanical” response might be evident as well as a
“regenerative” response of the afflicted skin.
In terms
of the “mechanical” perspective, one might speculate that the focused
extracorporeal shockwave has somewhat disrupted either the fat
components or the septae or both, which might lead to a smoothening of
the afflicted skin. MR imaging has shown that fibrous septa are
visualized in 97% of the area with cellulite depressions, which are
markedly thickened in cellulite afflicted areas [21]. Shockwave energy might have weakened the fibrous septae and thus the afflicted skin became smoother.
Reduction
of lymphedema is a second potential underlying mechanism. Recently, a
significant reduction of lymphedema was reported clinically following
four ESWT sessions in females with secondary lymphedema following breast
cancer treatment [6].
In animal experiments ESWT and the vascular endothelial growth factor
(VEGF-C) hydrogel appear to exert a synergistic effect in promoting
lymphangiogenesis [22].
On
the other hand, ESWT might somewhat influence mesenchymal stem cells.
There is evolving experimental data suggesting that shockwave therapy
activation pathways in adipose-derived stem cells [23].
Clinically, diseased skin appears to normalize following shockwave
treatment such as in progressive systemic sclerosis with an up
regulation of endothelial progenitor cells and circulating endothelial
cells [24].
Energy flux density of the focused ESWT is another issue to concern. We used low to medium energy flux densities of 0.35 mJ/mm2
with 1,000 impulses on each thigh with 4 Hz. To date, we do not know in
controlled trials whether potentially higher energy flux densities such
as up to 1.24 mJ/mm2 might be even more beneficial in terms
of the potential disruption of the fibrous septae in the
cellulite-afflicted areas. On the other hand, stem-cell activation might
be achieved by rather low-energy flux densities in regard of the
aforementioned potential underlying “regenerative” mechanisms.
To date, only small size, controlled trials with wide CIs have been published [7, 25].
We tried to overcome the methodological shortcomings of previous trials
in CelluShock-2009. In regard to different techniques, there are
evolving clinical data that, for example, low-level laser therapy with
532 nm wave lengths appears to improve cellulite in a double-blind,
placebo-controlled, randomized trial [26]. 1,064 nm Nd:YAG laser appears to improve mild to moderate cellulite also [27]. Radiofrequency is able to reduce cellulite in a randomized trial [28].

Limitations

Given
our randomized, double-blinded clinical trial, some limitations have to
be considered when interpreting our data. First, the extent of
cellulite reflected by digital unprocessed images assessed by two
independent examiners was chosen to overcome some types of biases.
However, a digital image does not necessarily reflect or even replace a
clinical examination including a pinch test. However, we sought to
address as objective as possible the outcome based on digital images.
Those images were produced by a clinical plastic surgical professional
photographer under the very same circumstances to overcome issues such
as angle of the photograph, lighting, among others. To date, we can only
report the short-term results 3 months following ESWT. We do not know
the long-term effects in terms of efficacy and sustainability of six
sessions of focused ESWT in cellulite to date.

Conclusion

The combination of focused ESWT (0.35 mJ/mm2,
2,000 impulses, 6 sessions) with gluteal strength training was superior
to SHAM-ESWT and gluteal strength training in moderate to severe
cellulite in terms of the CSS in a RCT. The mean improvement was 24% in
the intervention in contrast to the control group. Second, the SHAM-ESWT
and gluteal strength training were not able to change the CSS in a
3-month perspective. Long-term data are warranted to elucidate the
sustainability of the aforementioned clinical effects.

Electronic supplementary material

Acknowledgments

Prof.
Knobloch is the guarantor for this article and takes responsibility for
the integrity of the work as a whole. Article processing charges are
supported by Storz Medical AG, Tägerwilen, Switzerland.

Conflict of interest

The
principal investigator K. Knobloch has been a speaker for Storz Medical
AG (Tägerwilen, Switzerland) after the end of this
randomized-controlled trial on various indications for ESWT which had no
influence on this RCT.
B. Joest, R. Krämer, and P. M. Vogt declare no conflict of interest.
No company had any financial or intellectual influence on the design, the execution or the results of this RCT.

Compliance with ethics guidelines

This
RCT was approved May 22, 2009 by the ethics institutional review board
at Hannover Medical School, Germany, under the German title
“Stosswellentherapie und Krafttraining zur Therapie der Cellulite—eine
randomsiert-kontrollierte Studie” (Nr. 5206). The study is
internationally registered at ClinicalTrials.gov with ClinicalTrials.gov
identifier: NCT00947414.
All
procedures followed were in accordance with the ethical standards of the
responsible committee on human experimentation (institutional and
national) and with the Helsinki Declaration of 1975, as revised in 2000
and 2008. Informed consent was obtained from all patients for being
included in the study and for the publication of patient photographs.

Open Access

This
article is distributed under the terms of the Creative Commons
Attribution Noncommercial License which permits any noncommercial use,
distribution, and reproduction in any medium, provided the original
author(s) and the source are credited.

Footnotes

ClinicalTrials.gov identifier: NCT00947414.

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