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Mesotherapy: a bibliographical review
Fernanda Oliveira Camargo Herreros 1 Aparecida Machado de Moraes 2
Paulo Eduardo Neves Ferreira Velho 3
Abstract: Intradermotherapy is a medical procedure introduced by Pistor in 1958 that consists in the application 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 diseases and unaesthetic conditions. Medical clinics have been recently offering the treatment of intradermotherapy, 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 necessary 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 e um procedimento medico introduzido por Pistor, em 1958, e consiste na aplicacao, diretamente na regiao a ser tratada, de injecoes intradermicas de substancias farmacologicas muito diluidas. Esse metodo e capaz de estimular o tecido que recebe os medicamentos tanto pela acao da punctura quanto pela acao dos farmacos, e apregoa-se que sua vantagem e evitar o uso de medicacao sistemica.
Ha relatos da utilizacao da intradermoterapia para tratamento de doencas dolorosas, dermatoses e condicoes consideradas inesteticas. Atualmente, clinicas medicas oferecem esse tratamento, utilizando, porem, o nome mais popular para essa pratica, mesoterapia. Ha escassa informacao cientifica sobre o tema publicada em periodicos indexados no MedLine e poucos estudos com metodologia mais rigorosa sobre a eficacia e o mecanismo de acao da via intradermica. A maioria das publicacoes indexadas sobre esse tema versa sobre as complicacoes dessa tecnica. As dermatoses inesteticas tem se tornado queixas frequentes nos consultorios dermatologicos, sendo necessario um embasamento cientifico para lidar com tais pacientes, os quais, muitas vezes, estao em busca das novidades mostradas atraves da midia. Assim, ha necessidade de estudos cientificamente bem conduzidos sobre essa tecnica. Estes estudos deverao oferecer aos medicos elementos para esclarecer os pacientes sobre quais beneficios esperar e quais os riscos de tal abordagem.
Desse modo, realizou-se uma revisao bibliografica sobre o assunto e constatou-se a necessidade de novos estudos com metodologia adequada para a confirmacao dos beneficios da intradermoterapia como ferramenta util no tratamento dermatologico.
Palavras-chave: Injecoes intradermicas; Pele; Revisao; Terapeutica
Approved by the Editorial Board and accepted for publication on 25.05.2010.

Study conducted at the University of Campinas (UNICAMP), Campinas, Sao Paulo, Brazil.
Conflict of interest: None / Conflito de interesse: Nenhum
Financial funding: None / Suporte financeiro: Nenhum
1 PhD., Voluntary Investigator, Dermatology Department, University of Campinas (UNICAMP), Campinas, Sao Paulo, Brazil.
2 Adjunct Professor, Dermatology Department, University of Campinas (UNICAMP), Campinas, Sao Paulo, Brazil.
3 PhD., Professor and Coordinator of the Dermatology Department, University of Campinas (UNICAMP), Campinas, Sao Paulo, Brazil.
c2011 by Anais Brasileiros de Dermatologia 96 REVIEW
An Bras Dermatol. 2011;86(1):96-101.
An Bras Dermatol. 2011;86(1):96-101.
Mesotherapy: a bibliographical review 97

INTRODUCTION
Intradermotherapy is a medical procedure introduced by Pistor in 1958 which consists in the application of intradermal injections of pharmacological substances that have been diluted and which are given directly into the region to be treated.
The event that introduced the intradermotherapy technique is well-known. Pistor saw a patient with an asthma attack and administered intravenous procaine, hoping to obtain bronchodilation. Besides asthma, the patient had chronic hearing loss. The following day, the patient returned and told the doctor that after forty years of deafness, he was again able to hear the church bell, which was attributed to the injection he had received. The patient requested a repeat injection of the same substance, since his hearing had improved for only a short period. The doctor readministered intradermal injections of this product into the mastoid region and the patient once again experienced temporary hearing gain. The doctor continued with injections of procaine in various patients and, in 1958, he published his conclusions in “La Presse Medicale,” an article entitled “Expose sommaire des proprietes nouvelles de la procaine local en pathologie humain” (Review of new properties of topical procaine in human pathology).
1 In this article he described his experience in treating deafness, tinnitus, vertigo, presbyopia and headaches by using local injections of procaine. He supposed that the effects stood to reason because of the neurosensory stimulation caused by procaine, even though it had a short duration. Pistor believed that this therapy model based on intradermal injections was so important that it deserved its own name – mesotherapy – in view of the embryologic origin of the skin.

LITERATURE REVIEW
Despite the fact that this is the most wellknown event in the history of intradermotherapy, one must remember that experiments conducted earlier came before Pistor’s experiment. These experiments were mentioned by Rotunda and Kolodney in 2006 in a review article: in 1884, Koller, an ophthalmologist, related his experience with the use of local cocaine to manage pain. In 1904, Einhorn discovered a new anesthetic with a low risk of drug dependence: procaine.
In 1925, Lerich applied intradermal injections in the intercostal spaces. In 1937, Aron published a study about an intradermal injection of a histamine solution and concluded that intradermal injections of whatever product, when given into a painful location, would have an analgesic effect.3 However, it was with Pistor that intradermotherapy received more attention, when he founded the French Society of Mesotherapy in 1964 and the technique became known throughout the world. In 1976, Pistor succinctly defined this technique with the following words: “ A little volume, a few times, and in the right place.” The founder of mesotherapy realized that these recommendations were empirical and based on his personal clinical experience. He affirmed the belief that larger doses do not improve clinical results, and that multiple punctures seem to be better than fewer injections.
Intradermotherapy has always been described in articles as an intradermal injection of highly diluted drugs, making it more suitable to be used this way.
The dermis, therefore, started to be viewed as a location where products could activate dermal receptors and which would diffuse them slowly using the microcirculation unit. However, these explanations seem to be repetitious of the citations of his predecessor, although they are always referred to in the same way in subsequent articles.
The basic course of action of intradermal injections greatly varies from one study to another, and this may reflect a lack of methodological patterns which sustain mesotherapy. The articles commonly describe mesotherapy as consisting of intradermal or subcutaneous injections of a medical substance or a mixture of various products, called “melange.” Views about the injection of the needle into the skin, however, vary from one author to the other and are described as either being perpendicular or forming an angle of 30-60 degrees.7-13 There is, however, agreement between these authors that the needle should penetrate no more than 4mm. To reach this depth, it is necessary to use a Lebel needle (bevel
4mm long). The injections should be contained within the area to be treated and the distance between them varies between 1cm (at the minimum) and 4cm (at the maximum). The applications reported in the articles are done weekly or monthly, and the number of sessions reported vary from four to ten. It is suggested that small amounts be given per puncture.
Besides the traditional needle-syringe combination, more sophisticated and more expensive instruments may be used, such as the mesotherapy gun. These guns electronically inject multiple points and allow a controlled amount and depth of application. The disadvantage of this system is the difficulty in sterilizing the complete apparatus, because only the needle is disposable.
Of all the parameters described, it appears that the only aspect that has been scientifically researched is the depth of injections in mesotherapy. It has been shown that the intradermal route contains its own pharmacokinetics and, for this reason, it is recom


1. Fertil Steril. 2011 May;95(6):2134-6, 2136.e1. Epub 2011 Jan 5.
Abdominal mesotherapy injection extended the absorption of follicle-stimulating hormone.
Hsu CC, Kuo HC, Hsu CT, Gu Q.
Department of Obstetrics and Gynecology, National Taiwan University Hospital,
Taipei, Taiwan. tube2363808@gmail.com

Abdominal mesotherapy injection of recombinant human FSH (rhFSH) was well tolerated with increased net absorption (AUC0-∞ 4,655.3 IU•h/L and t1/2 247.6 h) up to 360 hours compared with those of 120 hours (AUC0-∞ 1,915.7 IU•h/L and t1/2 101.8 h). The extended absorption of rhFSH suggests that abdominal mesotherapy injection mode be considered for future administration of rhFSH in controlled ovarian hyperstimulation.


PMID: 21208615  [PubMed - indexed for MEDLINE]
2. Clin Dermatol. 2008 Mar-Apr;26(2):177-81.
Biorejuvenation: theory and practice.
Iorizzo M, De Padova MP, Tosti A.

Department of Dermatology, University of Bologna, 40138 Bologna, Italy.
matildeiorizzo@hotmail.com

The aim of mesotherapy for skin rejuvenation is to increase the biosynthetic capacity of fibroblasts, inducing the reconstruction of an optimal physiologic environment, the enhancement of cell activity, and the synthesis of collagen,
elastin, and hyaluronic acid. The desired final effect is a firm, bright, and moisturized skin, and the injection in the superficial dermis of suitable products--perfectly biocompatible and totally absorbable--can achieve these results. In addition to a daily sunscreen application and nonsmoking, mesotherapy is another antiaging strategy helping to maintain a globally firm and bright skin, protecting it from the environmental contributors to aging.



PMID: 18472058  [PubMed - indexed for MEDLINE]
3. J Drugs Dermatol. 2008 Apr;7(4):341-5.
An evidence-based assessment of treatments for cellulite.
Wanner M, Avram M.
Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. mwanner@partners.org

Cellulite, a skin surface change that is nearly ubiquitous in women, is a condition that remains elusive to treatment. In fact, no treatment is completely successful as none are more than mildly and temporarily effective. Despite the lack of evidence to support efficacy, treatment options continue to proliferate.  This article will briefly review the currently available data about cellulite treatments including noninvasive devices such as massage, radiofrequency, and laser and light-based treatments; invasive modalities including liposuction, mesotherapy, and subcision; and other treatments including topical creams and carboxy therapy.



PMID: 18459514  [PubMed - indexed for MEDLINE]
4. Rev Rhum Mal Osteoartic. 1990 Jul-Sep;57(7-8):589-91. [Controlled trial of injectable diclofenac in mesotherapy for the treatment of tendinitis].

[Article in French]
Menkès CJ, Laoussadi S, Kac-Ohana N, Lasserre O. Service de Rhumatologie A, Hôpital Cochin, Paris.
PMID: 2281303  [PubMed - indexed for MEDLINE]