▲EVIEW Abstract: Intradermotherapy is a medical procedure introduced by Pistor in 1958 that consists in the appli- cation of intradermal injections of diluted pharmacological substances that are given directly into the region to be treated. There are reports of the use of intradermotherapy to treat painful diseases, skin disea- ses and unaesthetic conditions. Medical clinics have been recently offering the treatment of intradermo- therapy, using the more popular name for this practice - mesotherapy. There is only scant scientific information about this subject published in periodicals indexed on MedLine. Only a few states rigorously pursue this method. Most indexed publications about this subject deal with the complications of this technique. Unaesthetic dermatoses have been a common complaint in dermatologic clinics, and it has become neces- sary to have scientific evidence to give to patients. Therefore, well-researched scientific studies about this technique are necessary to offer data to medical professionals that will clearly explain to patients both the benefits and the risks of these procedures. A bibliographical review was conducted and we verified the need for new studies with adequate methods to confirm the benefits of intradermotherapy as used in dermatologic treatment. Keywords: Injections, intradermal; Review; Skin; Therapeutics Resumo: A intradermoterapia é um procedimento médico introduzido por Pistor, em 1958, e consiste na aplicação, diretamente na região a ser tratada, de injeções intradérmicas de substâncias farmacológicas muito diluídas. Esse método é capaz de estimular o tecido que recebe os medicamentos tanto pela ação da punctura quanto pela ação dos fármacos, e apregoa-se que sua vantagem é evitar o uso de medicação sistê- mica. Há relatos da utilização da intradermoterapia para tratamento de doenças dolorosas, dermatoses e condições consideradas inestéticas. Atualmente, clínicas médicas oferecem esse tratamento, utilizando, porém, o nome mais popular para essa prática, mesoterapia. Há escassa informação científica sobre o tema publicada em periódicos indexados no MedLine e poucos estudos com metodologia mais rigorosa sobre a eficácia e o mecanismo de ação da via intradérmica. A maioria das publicações indexadas sobre esse tema versa sobre as complicações dessa técnica. As dermatoses inestéticas têm se tornado queixas frequentes nos consultórios dermatológicos, sendo necessário um embasamento científico para lidar com tais pacientes, os quais, muitas vezes, estão em busca das novidades mostradas através da mídia. Assim, há necessidade de estudos cientificamente bem conduzidos sobre essa técnica. Estes estudos deverão oferecer aos médicos elementos para esclarecer os pacientes sobre quais benefícios esperar e quais os riscos de tal abordagem. Desse modo, realizou-se uma revisão bibliográfica sobre o assunto e constatou-se a necessidade de novos estudos com metodologia adequada para a confirmação dos benefícios da intradermoterapia como ferra- menta útil no tratamento dermatológico. Palavras-chave: Injeções intradérmicas; Pele; Revisão; Terapêutica
Approved by the Editorial Board and accepted for publication on 25.05.2010. * Study conducted at the University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
Conflict of interest: None / Conflito de interesse: NenhumFinancial funding: None / Suporte financeiro: Nenhum
PhD., Voluntary Investigator, Dermatology Department, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
Adjunct Professor, Dermatology Department, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
PhD., Professor and Coordinator of the Dermatology Department, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
2011 by Anais Brasileiros de Dermatologia
An Bras Dermatol. 2011;86(1):96-101.Mesotherapy: a bibliographical reviewINTRODUCTION
ed the French Society of Mesotherapy in 1964 and the
introduced by Pistor in 1958 which consists in the
technique became known throughout the world.
application of intradermal injections of pharmacolog-
In 1976, Pistor succinctly defined this tech-
ical substances that have been diluted and which are
nique with the following words: “ A little volume, a
given directly into the region to be treated.1,2
few times, and in the right place.” The founder of
The event that introduced the intradermother-
mesotherapy realized that these recommendations
apy technique is well-known. Pistor saw a patient with
were empirical and based on his personal clinical
an asthma attack and administered intravenous pro-
experience. He affirmed the belief that larger doses do
caine, hoping to obtain bronchodilation. Besides asth-
not improve clinical results, and that multiple punc-
ma, the patient had chronic hearing loss. The follow-
tures seem to be better than fewer injections.1
ing day, the patient returned and told the doctor that
Intradermotherapy has always been described
after forty years of deafness, he was again able to hear
in articles as an intradermal injection of highly diluted
the church bell, which was attributed to the injection
drugs, making it more suitable to be used this way.
he had received. The patient requested a repeat injec-
The dermis, therefore, started to be viewed as a loca-
tion of the same substance, since his hearing had
tion where products could activate dermal receptors
improved for only a short period. The doctor re-
and which would diffuse them slowly using the micro-
administered intradermal injections of this product
circulation unit. However, these explanations seem to
into the mastoid region and the patient once again
be repetitious of the citations of his predecessor,
experienced temporary hearing gain. The doctor con-
although they are always referred to in the same way
tinued with injections of procaine in various patients
in subsequent articles.1,2,4,5,6,7 The basic course of action
and, in 1958, he published his conclusions in “La
of intradermal injections greatly varies from one study
Presse Medicale,” an article entitled “Exposé som-
to another, and this may reflect a lack of methodolog-
maire des propriétés nouvelles de la procaine local en
ical patterns which sustain mesotherapy. The articles
pathologie humain” (Review of new properties of top-
commonly describe mesotherapy as consisting of
intradermal or subcutaneous injections of a medical
In this article he described his experience in
substance or a mixture of various products, called
treating deafness, tinnitus, vertigo, presbyopia and
“mélange.” Views about the injection of the needle
headaches by using local injections of procaine. He
into the skin, however, vary from one author to the
supposed that the effects stood to reason because of
other and are described as either being perpendicular
the neurosensory stimulation caused by procaine,
or forming an angle of 30-60 degrees.7-13 There is,
even though it had a short duration. Pistor believed
however, agreement between these authors that the
that this therapy model based on intradermal injec-
needle should penetrate no more than 4mm. To reach
tions was so important that it deserved its own name
this depth, it is necessary to use a Lebel needle (bevel
– mesotherapy – in view of the embryologic origin of
4mm long). The injections should be contained with-
in the area to be treated and the distance betweenthem varies between 1cm (at the minimum) and 4cm
(at the maximum). The applications reported in the
Despite the fact that this is the most well-
articles are done weekly or monthly, and the number
known event in the history of intradermotherapy, one
of sessions reported vary from four to ten.2,7,13,14 It is
must remember that experiments conducted earlier
suggested that small amounts be given per punc-
came before Pistor’s experiment. These experiments
were mentioned by Rotunda and Kolodney in 2006 in
Besides the traditional needle-syringe combina-
a review article: in 1884, Koller, an ophthalmologist,
tion, more sophisticated and more expensive instru-
related his experience with the use of local cocaine to
ments may be used, such as the mesotherapy gun.
manage pain. In 1904, Einhorn discovered a new
These guns electronically inject multiple points and
anesthetic with a low risk of drug dependence: pro-
allow a controlled amount and depth of application. 6
caine. In 1925, Lerich applied intradermal injections
The disadvantage of this system is the difficulty in ster-
in the intercostal spaces. In 1937, Aron published a
ilizing the complete apparatus, because only the nee-
study about an intradermal injection of a histamine
solution and concluded that intradermal injections of
Of all the parameters described, it appears that
whatever product, when given into a painful location,
the only aspect that has been scientifically researched
is the depth of injections in mesotherapy. It has been
However, it was with Pistor that intrader-
shown that the intradermal route contains its own
motherapy received more attention, when he found-
pharmacokinetics and, for this reason, it is recom-
An Bras Dermatol. 2011;86(1):96-101.Herreros FOC, Moraes AM, Velho PENF
mended that injections not be given with a depth
for the same amount of time. Thus, it has been con-
cluded that the diffusion of a product in intrader-
A theory has been suggested, through a study of
motherapy depends upon the depth to which it is
cintilography, standardizing mesotherapy.16
injected. This difference can be illustrated with elimi-
authors of this research studied sixty patients with
nation curves: the superficial intradermal path would
neuralgia and used radioisotopes with a product to be
have a monoexponential elimination curve, while the
injected. The injections were given manually, with a
deeper intradermal path would have a biexponential
depth of 1.5 to 2 mm. The researchers concluded
curve (quicker initial elimination, corresponding to
that, at this level, the local activity of the product
an intravenous injection, followed by slower elimina-
would last longer. The authors affirmed that there is a
persistent reservoir with weak local diffusion in the
However, as mentioned earlier, most of the
dermis, but that the products injected into the dermis
research done on intradermotherapy in indexed jour-
reach great distances (passing progressively through
nals relates to complications. The most feared and
the circulatory system). Because of this evidence, the
most often reported complication is mycobacterial
researchers concluded that intradermotherapy func-
infection, which requires months of treatment with
tions with two factors: the activity occurs over short
multiple drugs and generally results in unaesthetic
distances (by stimulating dermal receptors in situ)
scars.18-32 Apparently, secondary infections described in
and the activity occurs over long distances (by reach-
the aforementioned works can be explained by inade-
ing other organs by way of circulation). In this way,
quate asepsis before the procedure or by contamina-
the diffusion of mesotherapy products has been
demonstrated. There is empirical evidence that
Other complications reported are: lichenoid
explains the mechanics of the process of mesotherapy
eruption,33 induction of psoriasis,34 urticaria,35,36 cuta-
by stimulating both near and far receptors. This is the
neous necrosis, systemic lupus erythematosus,37 pan-
running theory accepted by the French Society of
niculitis,38 acromia, atrophy and others.2,39-43 These
complications are attributed to poor techniques or to
On the basis of this theory, a concept has been
developed which is often cited in intradermotherapy:
Tennstedt and Lachapelle (1997) further report-
the concept of meso-interface, which is the surface of
ed that neither alcohol nor oil-based substances are
contact established between the injected products and
recommended for mesotherapeutic use because of
the tissue injected. The more fragmented the sub-
stance injected (multiple punctures with the smallest
Initially, mesotherapy research addressed the
possible quantity), the greater the meso-interface and
treatment of painful illnesses. Therefore, research
the greater the number of dermal receptors activated.16
indicates the use of intradermotherapy with benefits
In addition to this study by Kaplan and Coutris,
in the treatment of tendonitis,11 cervicobraquialgia,44
others also have been conducted, evaluating the
muscular-skeletal illnesses,15 and oral and periodontal
importance of the depth of injection in the diffusion
pain.8,45 A random study has been conducted compar-
ing the efficacy of mesotherapy and laser treatment for
In 1992, Mrejen conducted research to estab-
deep, sharp lumbar pain with dysfunctional sacroiliac,
lish if there was a difference between the diffusion of
with positive results for the injections.46 Another
products injected into the dermis at up to 4 mm or at
report indicates that pain was adequately controlled
10 mm of depth. He concluded that a product inject-
by substituting one session of mesotherapy for anti-
ed up to a depth of 10 mm diffuses more rapidly and
inflammatory prescription for post-operative dental
reaches the circulatory system more quickly, while at
surgery.10 A review article cites mesotherapy as an
the same time lasting shorter than when given at less
alternative to treatment for joint pain.9 These studies
than 4 mm. Because of this study, it has been suggest-
have one fact in common - the presentation of intra-
ed that injections in intradermotherapy be given at a
dermotherapy as an alternative to pain therapy – and
depth of 4 mm (so that the product will remain longer
this indicates the need for more research about this
The more superficial the injection, the slower
In 2001, indexed studies began to appear in
the diffusion, resulting in increased time in the upper
MedLine regarding the use of intradermotherapy for
dermis. Fifty percent of the amount of the pharmaceu-
tical injected at less than 4 mm of depth remains at
There are reports of lipolitic injections (deoxy-
the point of injection after ten minutes, while only six-
cholate or phosphatidylcholine) being given subcuta-
teen percent of the pharmaceutical injected at more
neously, in the name of mesotheraphy, to try to dimin-
than 4 mm of depth remain at the point of injection
ish the layer of fat in areas such as the abdomen, infe-
An Bras Dermatol. 2011;86(1):96-101.Mesotherapy: a bibliographical review
rior eyelids, neck, buttocks or thighs.47-49 Some studies
silanol in comparison with the dermis that received a
have been revised regarding the role of mesotherapy
physiological solution. Intradermotherapy with
in gynoid lipodystrophy 50 and others regarding the
organic silicon increased the number of collagen and
role of mesotherapy lipolysis.3,6,51 These revisions offer
elastic fibers in the dermis and improved the texture
the conclusion that, theoretically, a subcutaneous
of collagen on the side that received silicon.55
injection of specified products can function, but they
The conclusions of the study on intrader-
lack indexed scientific publications on which to base
motherapy are still pending. The study by Herreros etal. (2007) is, as far as the authors can tell, the first
In 2004, Rotunda et al. published a study in
work with a rigorous method published in an indexed
which researchers injected two main components of a
medical journal and which 1) evaluates the histologi-
lipolytic product (phosphatidylcholine and sodium
cal consequences of mesotherapy procedures, 2)
desoxicholate) used for subcutaneous injections.
demonstrates a significant increase in the number of
With the use of pork fat tissue, they concluded that
collagen and elastic fibers, and 3) shows improvement
the active ingredient of the product is sodium desoxi-
of the dermal texture after intradermotherapy. In spite
cholate and that this acts as a detergent, causing
of using women with moderate photoaging, it was not
unspecified lise of adipocyte cell wall.52 In 2005, Rose
the purpose of this study to evaluate intradermother-
and Morgan published a study demonstrating
apy as a treatment for this condition. The decision to
anatomical pathological exams of biopsies from one
use skin with photoaging in this study was made
patient after treatment with phosphatidylcholine and
because an earlier study had been published suggest-
sodium desoxicolato. Histology demonstrated inflam-
ing the use of intradermotherapy with organic silicon
mation and necrosis in the adipose tissue.53
in women with this condition. Still, the results of this
Conceptually, it is argued that if the technique
study suggested that women with only a small amount
is mesotherapy, then the number of punctures and
of elastic fibers were those who gained more fibers in
the amount injected subcutaneously should not cor-
the underarms that received silicon. This was further
respond to the traditionally recognized methods as
confirmed by Spearman’s rank correlation coefficient
specified by intradermotherapy. Even though subcuta-
- women with fewer elastic fibers in their underarms
neous injections fall under the definition of mesother-
who received physiological solution showed an
apy, as subcutaneous tissue is also derived from the
increase in the number of elastic fibers on the side
mesoderm, larger doses and a smaller number of
with silicon. The authors were able to separate the
puncture points will not yield the same results as
effects of puncturing from the effects of mesotherapy
claimed by Pistor, the founder of this technique.3
medication. Traditionally, it had been declared that
In 1992, also in an unindexed publication,
the therapeutic effect of this technique was a result of
Aumjaud recommended organic silicon for intrader-
combined medication and stimulation by needles and
mal use in age wrinkles and skin with rhytids and pho-
that the effects of both could not be distinguished.
toaging. The study used organic silicon associated
Injecting organic silicon into one side and physiologi-
with other substances, and the author did not men-
cal solution into the other and obtaining an increase
tion any scientific study that supported his recom-
in the number of fibers on the side injected with
mendation, but instead spoke of his own experi-
silanol proves that the effect of silicon is more signifi-
Maya, in a review article published in 2007,
More than three years since this study was con-
cited organic silicon as an intradermal medication
cluded, there have not been any complications in the
able to stimulate the synthesis of collagen.7
Food rich in fiber, such as vegetables and whole
As mentioned before, a previous study has been
grains, is a major source of silicon in the diet. Doses
published in an unindexed periodical describing the
up to 50 mg per day of organic silicon supplements
benefits of mesotherapy for gynoid lipodystrophy.
However, the author used a mix of products and his
In 2007, a study published in an indexed jour-
criterion to evaluate improvement was the loss of
nal histologically compared the skin of women with
measures (clinical evaluation and size), which makes a
moderate photoaging submitted to intradermal injec-
rigorous analysis difficult.15 One can question if the
tions of salicylate silanol and physiological solution.
loss of measures is adequate to evaluate gynoid lipody-
The authors analyzed the density of collagen fibers
strophy and also the possibility of evaluating a treat-
and elasticity in the dermis injected with salicylate
ment based on a combination of products, since it
silanol in relation to the density of fibers in the dermis
would be difficult to determine which product is
that received a physiological solution. They also eval-
responsible for the result. Park et al., 2008, could not
uated the texture of the dermis that received salicylate
demonstrate the effectiveness of mesotherapy on body
An Bras Dermatol. 2011;86(1):96-101.Herreros FOC, Moraes AM, Velho PENF
contouring using computed tomography scans to
(four) and the time between the last application and
measure the cross-sectional areas and thickness of fat
the biopsy (two months) were different from those of
injected with a specific solution.57 Lacarrubba et al.,
the study by Herreros et al., 2007 (10 weekly sessions
2008, conducted a preliminary study to evaluate
and biopsy two weeks after the last session). 55
mesotherapy for skin rejuvenation and assessed the
The conclusion of this study about silicon and
subepidermal low-echogenic band through ultra-
intradermotherapy induced the use of silanol to treat
sound with cross-sectional B-mode scanning after mul-
atrophy scarring in a certain patient. She was treated
tiple intradermal microinjections of hyaluronic acid
with doxycycline for atypical mycobacteriosis that
salts weekly for four weeks. They showed that this
occurred in the locations of application of
could be an effective treatment for skin photoaging.58
hydrolipoclasia by using ultrasound. From a clinical
Brown, 2006, stressed that, to date, the effects
perspective, the results were partially satisfactory, and
of mesotherapy have not been scientifically evaluated.
the patient was sufficiently satisfied as she chose not
He pointed that there was no dosage standardization
Similarly to Atiyeh et al., 2008, we concluded
The only previous, more adequate, methodical
that until further studies are conducted, patients con-
work is the already cited study by Amin et al., 2006.13
sidering mesotherapy for cosmetic purposes must be
In this study, the authors discovered clinical benefits
aware that the substances currently being injected have
of mesotherapy for the treatment of facial photoaging
not been thoroughly evaluated for safety or efficacy. 61
in four monthly sessions and an increase in collagenin the treated area, which was evaluated through a
zone of repair. However, there was not a statistically
Since there are few indexed studies about the
significant increase. Although the methodology for
use of intradermotherapy and so many about its com-
evaluating the results was good, the technique devel-
plications, it is only natural to distrust dermatologists
oped by the authors has been criticized. It is unknown
in relation to this technique. More adequate method-
what product was used, although they have declared
ological studies need to be conducted so that the true
to have applied a mixture of hyaluronic acid and
value of intradermotherapy with useful procedures in
“multivitamins.” Besides this, the number of sessions
the practice of dermatology can be demonstrated.
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How to cite this article/Como citar este artigo: Herreros FOC, Moraes AM, Velho PENF. Mesotherapy: a biblio-graphical review. An Bras Dermatol. 2011;86(1):96-101. An Bras Dermatol. 2011;86(1):96-101.
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