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MESOTHERAPY

INTRODUCTION

Mesotherapy is an art of injecting small quantities of various medicinal preparations such as vitamins, minerals and other conventional drugs directly into the mesoderm to treat pathological conditions locally. It involves the administration of intradermal or subcutaneous injections of compounds to treat a variety of medical conditions and avoiding systemic adverse effects due to drugs. It appears to be a novel technique to administer medicines local to the pathology while the skin serves as a natural time- release system.

BACKGROUND OF MESOTHERAPY

The term mesotherapy (derived from Greek mesos. “Middle” and therapeia to treat medically) denotes injection of substances into middle layer of skin ( mesoderm) for medical purposes.

Historical aspects[1]

Mesotherapy was originally used to treat painful conditions using local procaine injections. Michael Pistor who coined the term mesotherapy is considered the father of mesotherapy. In his original article,he described treating deafness, tinnitus, vertigo and headaches using local injections of procaine. Earlier to this in 1884, Koller an ophthalmologist used local cocaine to relieve pain. In 1925 Lerich used intradermal injections in the intercostal spaces. In 1937 Aron studied the use of intradermal injections to have an analgesic effect. Albert Lemaire, a Belgian physician used procaine injections to treat trigeminal neuralgia. In 1952, Michel Pistor a French physician popularized mesotherapy to treat various conditions in dermatology,sports,traumatology and vascular disease chiefly as a pain-relieving therapy. He defined mesotherapyas a techniquethat was used to treat mesoderm,(primary germ layer that develops into connective tissue, muscle and the circulatory system). In 1953, Dr.Mario Lebel invented a 3mm length needle that could be used precisely for injection of substances into the dermis. In 1964, the French society of Mesotherapy was founded by Michel Pistor and use of mesotherapy was extended to treat cosmetic conditions.

The American influence was evident after Dr. Lionel Bissoon popularized the technique in North America. Despite the fact that mesotherapy is gaining popularity in aesthetic medicine especially for localized cellulite reduction, it continues to be a controversial topic and therefore requires cautious approach. The safety and efficacy of these mesotherapy remain ambiguous to patients and physicians alike. [2]

Applied basic science [1, 3]

The concept that led to discovery of mesotherapy is quite interesting. Pistor saw recovery of chronic hearing loss while treating a patient with procaineinjections for an asthma attack. Subsequent intradermal injections of this product into the mastoid region proved this effect to be true. However the depth of injection was considered important. This led the researchers to the fact that at a depth of 1.5 to 2mm the local activity of the product would last longer due to a persistent reservoir with weak local diffusion in the dermis whereas products injected into dermis would dissipate to greater distances.A product when injected intradermally acts in two ways. Firstly, by stimulating dermal receptors in situ and secondly, over long distances by reaching other organs via circulation. A concept of meso-interface exists which is the surface of contact established between the injected products and the tissue injected. The more the multiple punctures are made and the more fragmented products are delivered in small quantities, the greater the meso-interface and proportionately greater numbers of dermal receptors get activated.Pistor has always described this technique as follows. “A little volume, a few times and in the right place”. The idea was that by placing these products in the dermis, the skin acts as a reservoir for drugs to diffuse slowly via microcirculation to activate dermal receptors.

A general mechanism of action (based on the target site, dermis) and a specific mechanism of action (based on the ingredients used) has been proposed to explain the concept of mesotherapy. The dermis is considered to be common denominator for circulatory, neurological and immunological functions; and the general mode of action is believed to occur by correction of these altered functions. Individual drugs or agents target the specific indication of mesotherapy.

EQUIPMENTS

The various equipments used in mesotherapy are

1. Mesogun (Fig 1)
2. Mircromesotherapy device
3. Needleless Mesotherapy

Mesogun

Mesogun is a syringe infusion pump that is capable of injecting the desired substance at a required amount, speed and depth using the injector and needle. Syringes varying from 2cc-10cc and needle lengthsvarying in size from 4mm to 13mm can be used based on the indication, and desired depth of injection. A device known as guide is used to keep the needle at a constant depth. Once the parameters are chosen, the product can be injected by one of the following modes.

1. Continuous – Min 3cc/min Max 10cc/min.
2. Mircrodose – Max0.1cc/trigger.
3. Standard dose – Max 0.3cc/trigger.
4. Mesoperfusion – Max 0.3cc/trigger.
5. Nappage – 0.1cc/trigger.

Advantages of Mesogun

1. Good comfort level for patient and physician
2. Procedure is faster and relatively painless
3. Accurate delivery system
4. Versatality – Ability to perform various modes such as nappage, continuous, mesoperfusion in dosimetry.

Syringes used in Mesogun: Generally 1ml, 5ml, 10ml and 20ml syringes with luer lock system is used based on the indication.

MesoNeedles (Fig2 a): Mesoneedles or “Lebel needles” are commonly used in mesotherapy.The John Screw needles have an adjustable length.The recommended parameters for needles are based on the site of injection:

Face and neck – 4mm 30G mesoneedles

Fat and cellulite – 6mm 30G mesoneedles, ½ inch 30G needles.

Multi-injectors and plates (Fig2 b): These accessories help to cover larger areas in a short time facilitating faster and easier procedure for the injector. There are sterile circular and linear multi-injectors with needles ready to be used for any body part.

Micromesotherapy Device

Micromesotherapy is an evolution of conventional mesotherapy. Usually mesotherapy uses needles to deliver drugs in deep dermal layer. Here a reverse cone shaped device has ultrafine needle 32Gx2mm by which drugs are injected into the superficial layer of dermis therebyminimizing incidence of bruising, pain and scarring.

Needle-Less Mesotherapy or No Needle Mesotherapy

This is a needle free device that pushes mesotherapy products painlessly through the skin using electrical waves known as isophoresis. The main features of needle less mesotherapy are:

1. Less painful and less traumatic
2. Uses ultrasound/electroporation technology.
3. Probably around 20% efficiency compared to traditional mesotherapy as there is no neocollagenesis or neo angiogenesis reactions that occur with needle micro injury.
4. This may be an option if mesotherapy is not allowed in the country.

It has been discussed in details in Chapter 12.

MESO SOLUTIONS (Fig6[VG1]

The basic requirements of meso products is that it should be approved and skin-compatible.Systemic administration (intravenous, intramuscular, subcutaneous or intradermal) should be safe and known pharmacological actions to be effective. The ingredients used in mesotherapy products should be water soluble, isotonic and non-allergenic.

The mesoproducts vary with the indications chosen for treatment^. [4] [ Figure 3]Products used for mesotherapy involves combination of products some of which are main ingredients known as principals as they have high grade of evidence in the treatment of each indications and complementary agents that have been approved for treatment of each indications. For a mixture to be effective it should contain 2 – 3 principals for any given indication. Therefore the ingredients in mesosolutions are broadly classified into main categories:

• Principal (P) / Major
• Complementary (C) / Minor.

The main targets for mesotherapy are skin, hair, fat and cellulite. (Table 11.1).

Table 11.1 Principal and Complementary ingredients in meso solutions in various indications

DMAE -Dimethylaminoethanol ; PPC – Phosphatidylcholine

TECHNIQUES FOR MESOTHERAPY INJECTIONS

The mesoproducts can be injected into the skin by various injection techniques to reach desired depth.The commonly used techniques and the desired depth reached are summarized in Table 11.2and Illustration 11.1

Table 11.2: Techniques and depth in mesotherapy injections

The salient features of various techniques are outlined below:

Intra-epidermal

This is one of the most superficial of the techniques described by Perrin.

1. Depth: 1mm within the epidermis
2. Painless, no bleeding
3. Simple and large surface covered
4. Ideal for patients with low pain threshold
5. Ideal for facial rejuvenation, mesoglow

Papular

1. Depth:2mm dermoepidermal junction
2. Painful
3. Useful in mesobotox
4. Ideal treatment of wrinkles

Nappage(French for ‘covering’)

Also known as picotage is the classic injection technique in mesotherapy. (Illustration 11.2) It is the most widely used technique in aesthetic dermatology. The syringe is held obliquely and the physician applies constant pressure on the plunger flicks the wrist to infuse a drop of the solutioninto the dermis(Fig 4). The injections are 2-2.5mm deep and 1cm apart. This technique can also be used for injections using a mesogun. (Fig 5)

1. Depth 2-4mm
2. Less pain and less bleeding
3. Ideal for rejuvenation and scalp treatments

Point by Point(Fig 6)

1. Depth 4mm
2. Perpendicular injection
3. Ideal for fat reduction

Mesoperfusion

1. Depth > 4 mm
2. Mesosolution is injected slowly over a priod of 10 minutes
3. Not commonly used in dermatology

PRACTICAL ASPECTS OF MESOTHERAPY

Indications and contraindications for mesotherapy are listed in box 11.1 and box11.2.

Box 11.1 Indications for mesotherapy

Box 11.2 : Contraindications for mesotherapy

Patient selection

Selecting the patient with a valid indication for mesotherapy is the key to success. Care should be taken to avoid patients with active skin diseases, too elderly and patients with history of sensitive skin. For androgenetic alopecia better results are seen in patient with Grades 1 – 3.

Counseling and preparing the patient

A proper counseling is essential before starting mesotherapy. Patients with body dysmorphic disorders and those with unrealistic expectations should not be treated. Alternate procedures should be discussed sufficiently as mesotherapy is still in the controversial stage. A written informed consentis mandatory in the present medical scenario. A good before and after clinical photograph is needed to evaluate results following the procedure.

Procedural aspects

The area to be treated is marked and thoroughly cleaned with an antiseptic solution. For anesthesia, a local anesthetic cream may be applied or ice-anesthesia can be used to numb the treatment area. Patients are preferably injected in a lying down position. The required quantity of ingredients is drawn into the syringe using an 18Gx11/2needle. The injection is given either manually or using a device to deliver by the papular, nappage or point by point technique. A gentle massage is given after the treatments. Fresh normal saline and a mositurising cream can be applied to the treated area and massaged gently. [9]. The procedure takes about 20 – 30 minutes depending on the indication and area to be treated. There is no downtime after the procedure and the patient will be able to return to normal activities immediately.

Good results are seen with mesotherapy done for skin rejuvenation, cellulite and double chin. [Fig 7, 8, 9]

Post procedure care and counseling for follow up

There may be mild pain, pinpoint bleeding, itching, burning or erythema after the injection which will subside spontaneously. Bruising and hematoma can appear occasionally and can be managed symptomatically. Mild swelling at site of injection may require anti-inflammatory agents for few days.

The patients need to be counseled on the following aspects:

1. Avoid sun exposure and smoking for next 48 hours
2. Loose fitting clothes to be worn especially after lipolytic injections.
3. The area to be treated is generally massaged after 72 hours and continued daily till disappearance of nodules if any.

Follow up: Generally treatments are given once every 1-2weeks for 6 sessions, then once a month for 5months. Maintenance sessions are to be done once or twice a year. This protocol may be altered depending on the indication, patient’s lifestyle, financial position and response to

previous treatments.

Complications

Though there are few evidence based studies on the efficacy of mesotherapy, there are documented reports on various complications. [10-17] The complications can be classified as local and systemic complications. (Box 11. 3)

Box 11.3: Complications

Management of Complications:

Bruising: It is a common but preventable complication. Always advice patient to stop aspirin or NSAIDs at least 2 weeks prior to the day of procedure. While injecting be slow and gentle. It is advisable to avoid mesotherapy during menstruation.

Burning/Itching: Burning can be overcome by adding lignocaine to the products if compatible. A mesomask applied immediately following procedure can also minimize burning and itching as it has a soothing effect.

Pain/Tenderness: Procedural pain can be minimized by using adequate topical anaesthesia. Immediate post treatment pain can be alleviated by cold compresses with ice. Other methods that help to minimize pain are by pinching the skin for point by point injections or by stretching it when giving a nappage. Change needles after every few pricks to reduce the pain caused by blunt injecting needles

Urticaria: Urticaria can be avoided by a careful history to avoid products that would provoke an allergic reaction. E.g. phosphatidyl choline in individuals with history of allergy to soy proteins.

Skin necrosis: Skin necrosis occurs usually with phosphatidyl choline when the injections are given superficially <1cm below the epidermal surface, excessive injection volume at each point, or in appropriately small distances between the points.

Ulcers: Ulcers can due to infection or irritant nature of the drugs. Irritant induced ulcers can be prevented by minimizing the number of drugs used in the cocktail to 4 or 5. Infective ulcers can be avoided by disinfecting the treatment area thoroughly and by wearing sterile gloves and using sterile equipment and materials.

Hyper pigmentation: This can be avoided by advising the patient photo protection for 48 hours after the procedure and by addition of topical skin lightening agents in patients with a history of post inflammatory hyper pigmentation.

COMBINING MESOTHERAPY WITH OTHER TECHNIQUES

Mesotherapy can be combined with other techniques to enhance results.Soon after injection of mesotherapy products, ultrasound, radiofrequency or electroporation may be applied to help in better diffusion of the injected products. The techniques are discussed in chapter 12. Mesomasks can be applied immediately after the injections to minimize bleeding points and to overcome the discomfort that follows injections.It is a 150 g of powder to be mixed with water to form a paste which is applied for 15minutes as a mask over gauze. This allows all products to penetrate deeper in the skin to give a better effect. These masks contain a mixture of calcium sulfate, talc and orange oil. Other procedures such as chemical peels, fillers and neurotoxins can be carried out between the mesotherapy sessions.

In countries where mesotherapy is not practiced, mesotherapy products can be used following cosmetic skin needling. By using a dermaroller in the area to be treated, it is possible to create micro perforations that will be used as channels to deliver a product deeply into the skin.

CLINICAL STUDIES

Mesotherapy has been in history for a long time and there are proponents who have been successfully using it in practice for the benefits of their patients. However there are few indexed studies about the safety and efficacy of mesotherapy but many about its complications, hence it only natural to distrust proponents in relation to this technique Hence adequate controlled studies are needed to establish the value of mesotherapy in aesthetic dermatology. [18] Mesotherapy for skin rejuvenation, treatment of local fat deposits, body sculpting have been assigned Evidence Level C, whereas cellulite treatment has been assigned Evidence Level D [18].

Few recent studies have shown promising results for mesotherapy in various aesthetic indications. A study by Larruba et al showed good results with hyaluronic acid mesotherapy on photoaging and assessed by ultrasound techniques. [5] A study by Savoia etal showed promising

[VG1] An excellent compilation with evidence for few of them are given in these two articles from IJDVL

1. Sarkar R, Garg VK, Mysore V. Position paper on mesotherapy. Indian J Dermatol Venereol Leprol 2011;77:232-7
2. Konda D, Thappa DM. Mesotherapy: What is new?. Indian J Dermatol Venereol Leprol 2013;79:127-34

Another review of various indication s of mesotherapy is in this article by Dr. premlatha

3.Latha P. and Vandana K.R. / International Journal of Advanced Pharmaceutics / 1 (1), 2011, 19-29

( full text available of all three)

The meso solutions can be tabulated in the format below

1. Indication
2. Product
3. Mechanism of action ( should include original intention versus intention in mesotherapy e.g. aminophylline was originally used for brochodilation. In mesotherapy it is used for vasodilatation etc
4. Evidence grade ( wherever available)