Untitled

▲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 review INTRODUCTION
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 LITERATURE REVIEW
(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 et al. (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 CONCLUSION
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. REFERENCES
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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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