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REVIEW ARTICLE 129 Mesotherapy Thada Piamphongsant ■Mesoderm is a middle layer of tissue formed in the early developing embryo. Therefore the treatment at this skin layer is called mesotherapy. However the treatments sometimes extended to the superficial layer or deeper through internal organs. Thus, to understand the details of such therapy, we need to have an overview of the treatmentûs principle. To administer drugs through the skin and lower tissue layer, several medias are needed. A) Skin moisturization such as to moisture the skin with water or emollient, to cover by transparent plastics, or to use drug delivery patch which has occlusive effect. B) Chemical mixture such as DMSO, isopropyl myristate, propylene glycol. These chemicals will act as a penetration enhancers. C) Advance technology adapted to improve the penetration effect of the media. For example, the drug capsule is specially designed to have better penetration property or using some techniques to minimize the ªï∑’Ë 10 ©∫—∫∑’Ë 2 molecules of drugs such as liposome, nanosome. D) To change the condition of epidermis by using electromagnetic wave, microneedles or penetration of the drug through hair follicles. E) Application of electrical techniques, i.e. ionto, phono, sono or electromagnetic method. In dermatological study, magnesium ascorbyl phosphate cannot penetrate directly through the skin. It has to be modified by or combined with other methods e.g. iontophoresis-it has a synergistic effect on superficial melasma but not effective in deeper type. However superficial melasma can be cured by any bleaching creams and there is no need to use iontopheresis. In cosmetic dermatology vitamin C is generally used to treat melasma, however there is some limitation due to its fast deteriorating property. Though there are attempts using various technologies to stabilized vitamin C, the longest duration only lasts for 3 months. Stabilized vitamin C are used instead such as ascorbyl tetra-iso palmitate, or enveloped in º‘ « À π— ß µÿ≈“§¡ 2548 REVIEW ARTICLE 130 glycosphere. The selection of base substances is also important as it has an influence in the penetration of vitamin. It was found that vitamin C in oil-in-water base has better penetration than in water-in-oil base and to be in gel form is better than in cream.1 It was found that only a part of vitamin C structure is important to fibroblast but it was not possible for fibroblast to incorporate vitamin C. Fullerence-enveloped vitamin C which has similar structure to nanosphere might help in the penetration process. Fifty years ago due to poor penetration into the skin, some French doctors thought of why not inject vitamin C into the skin? Nowadays patients quest for the treatment methods. What they want are safe methods, no complication, no anesthetic, simple for both physicians and patients. But most of all it must be effective, fast and not expensive. Therefore anesthetic mesotherapy seems to answer the question. Mesotherapy is an advance technique of injection. Multiple injections at a time can be done with minimum pain. Drugs to be used can be varied depending on the pathology of diseases. Principles of mesotherapy are2 Right drug Right dose (not for which can create problems), and Right location (suitable depth) For example : ● Use of multivitamin, and hyaluronic acid for wrinkles. ● Use of botox for shallow wrinkle, so called mesobotox. Actually botox injection is a kind of ªï∑’Ë 10 ©∫—∫∑’Ë 2 mesotherapy. Technique Special needles are needed for mesotherapy injection, which are for the depth of 4, 6 and 13 mm. At the beginning, botox injection was more popular than that of mesotherapy, so the latter was used for other locations that botox could not be used by dissolving the drug at 5 times dilution. If using the standard botox injection, it may cause twisted face. ● There are 3 main drug groups used for getting rid of cellulite as follow : 1) The group that its effect is to increase penetration and dilate blood vessels such as theophylline. 2) The group that its effect is to dissolve fat by detergent substance : tween 80, deoxycholate. 3) Calcitonin. ● To eliminate extra fat at specific site by using phosphatidylcholine ● Inject vitamin C, Asia Cantella for acne scar, striae. ● Inject glutathione for melasma. ● Inject panthenol, zinc, minoxidil, or biotin for hair loss. Furthermore, mesotherapy can be used for other disorders such as arthritis, prohibit smoking habit, tension reduction, muscle inflammation and venous insufficiency. In fact, mesotherapy has been existing for more than 45 years and was used at the beginning for arthritis. It then was observed that cellulites around the injected sites also disappeared. The advantages of mesotherapy are as follows : - No deep cutting, no operation required. º‘ « À π— ß µÿ≈“§¡ 2548 REVIEW ARTICLE 131 µ“√“ß∑’Ë 1 Sites of injection. Level Epidermis Papillary dermis mm 0.1-0.3 0.5-1 Physicians Scratch test by allergist Intradermal test by allergist Intradermal 4 3 Dermatologist : intralesional Dermis-subcutaneous junction 6 Dermatologist : intralesional Subcutaneous Intramuscular Articular area 12 Dermatologist : intralesional GP, dermatologist (botox) Rheumatologist Mesotherapy IED (reju) ID (acne scar), dermal melasma, beading technique IDS (hair loss), Nappage technique IDP (cellulite), allergy injection DHD (obesity) Mesobotox Fibro-osseous junction, acupuncture pt. Remarks : IED = intraepidermal, ID = intradermal, beading technique (inject to pop a pimple), Nappage technique (see explanation in this text), IDS = intradermal superficialis, IDP = intradermal profundus, DHD = deep hypodermic, Acupuncture pt. = needle piercing - Low dose usage and precise localization - No complication to any part of the body. - Time release absorption3. Experimentally it was found that the penetration of substances that was injected at the upper dermis level is much better than at the deeper level as it slowly percolates. Such substances should be water soluble, neutral status, no allergic, natural, curable and safe. injection needle should be 4-6 mm in length. 4. Mesodrip : attach an adapter and slowly inject at one time with 3.5 gauge needles, and slowly push. 5. By using a mesosystem pistol, the depth of injection sites and the dosage can be adjusted equally or every spot of injection by using Nappage or single injection. List of drug group ■ Drug injection technique 1. Inject to intraepidermal site. 2. Nappage which is a rapid injection technique, by using one syringe to inject several times continuously into the dermis. 3. Single spot injection - Inject for dermatological purpose. This depends on the depth of clinical sites. - Inject is similar to immunological test. This creates a small wheal which is rather painful and is used to cure the deep scar. For deeper site, ªï∑’Ë 10 ©∫—∫∑’Ë 2 1. Anesthesia group : lidocain, xylocain 2. Arthritis : NSAIDs, calcitonin, analgesic group 3. Increase blood circulation group : buflomedil, pentoxyphyllin 4. Multivitamin 5. Stimulate immune system 6. Drug that effect to reduce tension on neuron system such as amitriptyline 7. Drug group to cure general disease in our body such as phloroglucinol º‘ « À π— ß µÿ≈“§¡ 2548 REVIEW ARTICLE 132 Pain killer Use lidocain when having pain anywhere and as soon as symptoms start. Use procain for chronic pain ● Dosage is 1/60 of edible drug ● May use analgesic, neuron-effect drug anti-inflammation drug : calcitonin ● When having pain from sprain and strain, use piroxicam plus lidocain. It was found that mesotherapy has more advantage than other treatments in many ways. For example : a symptom of tennis elbow can be improved by taking medicine within 3 months, by steroid injection within 2 weeks but by using mesotherapy, the patients can get better and may have some light exercise within the next day. If it is muscle pain, then use analgesic drug. For chronic pain use calcitonin Neural pain such as herpes zoster : inject spot by spot along the nerve line along the lower part of costal cartilage. ● Cellulite treatment To get rid of cellulite we need to know the pathway of lipid dissolution. There are 4 steps of treatment as follows : 1. To reduce water retention in fat cell by using dehydrated substance such as mannitol or by hand massage or using some instruments. Some massagers may claim that it is the way to release fat while its real effect is only to decrease water. 2. To smoothen blood circulation by applying drug that enlarge blood vessel such as pentoxyphyllin, PTMB [4-(1-pyrrolidimyl)-1-(2,4,6-trimethosyphenyl)1-butanone], buflomedil or electricity to warm up. ªï∑’Ë 10 ©∫—∫∑’Ë 2 Nowadays laser technique is used to hit the cellulite and using body wrap to warm up (but not to reduce fat). When the skin is warm water is released (not fat) temporarily for a few days. Therefore after a few days cellulite will return, except that the patient will do some exercise in combination with fasting. 3. Fat dissolution A) Using detergent. Similar to dish washing solutions that dissolve fat. The detergent emulsifies fat into small particle and turn to be fatty acid e.g. tween 80, deoxycholate. B) Using other substances such as phosphatidylcholine, calcitonin. C) Destroyed fatty acid by using carnitine and conjugated linoleic acid. D) Hibiscus extract can reverse chylomicron to triglyceride. E) Use additive that can react to c-AMP to dissolve fat to fatty acid such as coffee, theophylline. 4. To strengthen the destroyed tissue by using antioxidant mixed with silicium to renew the tissue. The injected solution might not be composed of all the essential active ingredients, so slimming cream is needed to apply on the skin lesion as well because it has all the ingredients. Some physicians might think that applying slimming cream is not necessary. However one should realize that most people do not like injection. By applying cream the ingredients can penetrate through the skin better. Most creams consist of transdermal delivery system which enhances drug delivery into the skin or the medicine absorption may be accelerated by covering the treated area with a transparent plastic during bedtime. We advice patient º‘ « À π— ß µÿ≈“§¡ 2548 REVIEW ARTICLE 133 to cover the treated area with thin transparent aluminum pads (see thru) to produce heat. The most important suggestion to patients is exercise and control diet otherwise the fat accumulation will return to the same level. Drug injection is only 70% effective, so a cream should also be applied. Problems in using phosphatidylcholine (PC) In USA this substance is classified as a food ingredient, not as a drug because it is made from egg yolk sac, not yellow eggs. Americans bought it from Brazil to extract contaminated substances off. In Thailand there are many problems about cellulite injection due to wrong injection technique, for example : - The person doing the procedure is not well trained and do not know the right depth of injection level. People think that they can just consult any pharmacist and they are not keen to study the proper method. - The drug imported from Brazil is not pure enough and are oil base. Actually, it should be water base which is the most suitable preparation. - Wrong drug mixture. Again, people just think they can ask the pharmacists or the personnel responsible for the product. So there are problems in applying mesotherapy in Thailand. After injection a patient will get granuloma. In the picture (Fig. 6), a woman used PC injection and got granuloma, which was probably due to over application. This substance cannot be injected at superficial dermis as it may cause skin necrosis and it can make people blind if the infection site is ªï∑’Ë 10 ©∫—∫∑’Ë 2 Fig. 6 Granuloma after PC injection. (see colored picture p. 216) near the eyes. The type of drug to be used also depends on the grading of cellulite. The International Physicians Association in Mesotherapy and most Americans do not recommend the use of PC due to the following reasons : 1) Create skin granuloma 2) Safety of drug use to cure cellulite cannot be guaranteed. 3) Other substances can also be used effectively. The fat dissolution effect is also not greater by using surfactant alone4 and even create more harm. For fat under eye lids it is suggested to consult the surgeon as the injection of phosphatidylcholine is too risky. Aesthetic mesotherapy 1. Applying hyaluronic acid, vitamins and other minerals have rejuvenation effect to the face sooner. 2. Alternative way is to use other substances to rejuvenate the face within 15 minutes. This is suitable for the ones with lots of wrinkles, especially movie stars. Other substances such as DNA, placenta, º‘ « À π— ß µÿ≈“§¡ 2548 REVIEW ARTICLE 134 proteo-chrondriotin sulfate is still on experimental ment effect in synthesizing collagen fibers together process. with other substances. Injection to acne scar : by using multi vitamin Hair loss therapy silicium and Asia cantella injection give better result. Several mixtures are used such as panthenol, biotin, zinc. Other substances such as finasteride, ■ Conclusion Mesotherapy is the technique originating in dutasteride and other hormones are still under reFrance and had been used to cure arthritis for more search. The danger in taking finasteride orally is than 60 years and to eliminate cellulite for 45 years. dangerous as there is 30% possibility that it can create The technique nowadays is used in America. In cancer of prostate gland while there is no evidence 2004, there were 5,000 trainees and the technique is of PSA (prostatic specific antigen) increment found. certified by American Board of Mesotherapy. In The size of prostate gland is still normal and can be Thailand, the proper technique usage should be diagnosed only by tissue biopsy with 30% chance to learned and the drugs should be selected for safe use. After reading this article and if there is any be.5 The treatment of Striae Distensae from preg- unclear information the reader may take a jet plane to America or France to see how advance they are nancy and over dose of steroid. Injection of Asia cantella extract has supple- or simply call the author at 0-2424-9619. ■ ‡Õ° “√Õâ“ßÕ‘ß ■ 1. Huh CH, Seo KI, Park JY, Lim JG, Eun HC, Park KC. A randomized, double-blind, placebo-controlled trial of vitamin C iontophoresis in melasma. Dermatology 2003;206:316-20. 2. Adelson H. Introduction to mesotherapy. Lecture note. 2004. Salt lake City, USA. 3. Rotunda AM, Suzuki H, Moy RL, Kolodney MS. Detergent effects of sodium deoxycholate are a major feature of an injectable phosphatidylcholine formulation used for localized fat dissolution. Derm Surg 2004;30:1001-8. 4. Thompson IM, Goodman PJ, Tangen CM, Lucia MS, Miller GJ, Ford LG, et al. The influence of finasteride on the development of prostate cancer. N Engl J Med 2003;349:215. 5. Kaplan AR. Devernir dûun produit Marque injecte par quatre voies differentes. Bulletin SFM; 1985. p. 62. ªï∑’Ë 10 ©∫—∫∑’Ë 2 º‘ « À π— ß µÿ≈“§¡ 2548