Included on DVD 
Introduction
The term ‘mesotherapy’ was reputedly first coined by journalists attending a lecture by Dr Michael Pistor, a French physician, in 1958. They mistakenly believed he was referring at the time to the mesoderm, an embryonic layer, and one of the three primary germ cell layers in the very early embryo, as opposed to injections into the dermis, the middle layer of the skin.
Dr Pistor’s principles were first enumerated in 1958. His system was at the time primarily used for medical and musculoskeletal disorders, and consisted of the need for:
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correct diagnosis
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the localized application of medications near the target organ
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the use of the smallest dose of pharmaceuticals for effective and localized treatment.
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During his lecture, Dr Pistor used the expression : “ I don’t know how, I don’t know why but it works.”
There are numerous theories that describe the mechanism of action. Some practioners believe in the reflexive theory, where the mechanism of action is due to the direct mechanical puncture, and chemical (or pharmacological) actions are a result of the action of the injected drugs. An alternative theory is microcirculation stimulation by the local injections close to the vessels damaged by the pathological process. In this theory the applications are made close to arterial paths with 1 or 2 cm in between the punctures. The third theory is Kaplan’s interface where molecules with low weight are absorbed by blood vessels and the high molecular weight molecules are absorbed by lymphatic vessels passing through lymphatic nodes.
In 1958 the French Academy of Medicine, endorsed mesotherapy as an integral part of traditional medical standards and in 1996 it was recognized by the National Health Agency of Accreditation and Evaluation in France.
The theory of mesotherapy is simple. The stratum corneum of the skin acts as an effective barrier to most large molecules, hence the paucity of pharmaceutical transdermal patches. In mesotherapy, the integrity of the stratum corneum is pierced, allowing the deposition of small amounts of pharmaceuticals. Numerous studies have demonstrated that molecules deposited in the epithelial dermal layer or the intradermal layer will be found in venous return for up to 8 hours, as opposed to 1 hour for subcutaneous injections. This prolonged exposure at the site of the target lesion leads to a more profound effect.
MATERIALS, NEEDLES AND SYRINGES
Needles
The needles generally used in mesotherapy are 30 g (29 mm) and 27 g (40 mm) with needle lengths ranging from 4 to 13 mm for cosmetic purposes. Generally a 5 cc syringe is used manually or with an injection device.
Injection Devices and Mechanical Syringe Support
In recent years, a large number of mechanical injection devices that can accurately control both the depth and speed of injection have been developed. The most common devices will be described below along with some of the benefits and drawbacks of these devices.
The ideal pistols should fulfill the following criteria:
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All the parts that have direct contact with the patient must be disposable
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The medication does not run inside the pistol but inside the syringe
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Must have mechanisms to calibrate depth of the needle and drug delivery
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Must have energy power or rechargeable battery
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Must be economic
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Must be ergonomic enough to allow injections in deferent angles and positions
Types of devices:
Den-Hub is a simple mechanical pistol fitted with a screw that determines the depth of injection and is activated by a simple trigger. It is an automatic device where a 10 mL syringe is plugged in.
Mesopen – this pistol operates on a lithium battery and both the depth and volume of substance to be delivered can be adjusted.
Mesalyse I – the Mesalyse I is composed of three components: a compressor, a control unit that can be programmed for both speed and depth of the injection and which can be set on a continuous or single injection mode, and a pistol with individual needles. The advantage of this device is that the speed of the injection can be modulated: increasing the speed decreases the patient’s discomfort.
U225 – this device is very similar in form and function to the Mesalyse I.
DHN 1, 2, 3 and 4 – offers various degrees of complexity with the DHN 3 being the most complete device. The injection is triggered by pressure of the pistol on the skin and enables injections in continuous mode or single shot.
Piso 4 – this is a battery-operated system that allows the frequency and volume of injection to be adjusted and has one unique feature – mesoperfusion. Mesoperfusion allows two to six needles to be fixed to tubing connecting to a device that will perfuse the chosen medication at a low pressure. This allows a large area to be perfused at a low, comfortable pressure, e.g. for cellulite. The disadvantage lies in the need to purge the tubing before each usage and the necessity of replacing the tubing each time, together with a requirement for service and cleaning by the manufacturer every 6 months. In the hands of a skilled practitioner mesotherapy can be performed manually with a simple syringe and needle. For novices, or if an assistant is to be taught, electronic pistols allow more control since the depth, volume, speed and frequency of the injection can be preset. Many of the devices do not fully retract the needle after penetration, causing superficial lacerations if the injector is ‘dragged’ across the face or body for continuous injection. This problem is found primarily with the use of needles made in the USA, which have less flexibility than many of the needles manufactured in Europe.
TECHNIQUES AND DEPTHS OF INJECTION
Intraepidermal Injection
Intraepidermal injection involves use of a 13 mm needle, which is is placed horizontally on the skin with the bevel facing upward. A series of injections to 1 mm depth is performed by a vertical flicking of the practitioner’s wrist on moving along the desired area. The needle must not be dragged between points of injection or abrasions will result. The product is not injected into the skin but the disruption of the stratum corneum allows for quick localized absorption. The punctures are placed 2–4 mm apart and the movement is sometimes described as a “parkinsonian” type of movement, this technique is referred to in French as ‘nappage’ .
Intradermal Superficial Injection
Intradermal superficial injection involves injection with a 6 mm needle at a depth of 1–2 mm. At this depth either point-by-point (PPP), which is a traditional injection technique, or nappage, with a total of 0.1 mL injected approximately at 1–2 mm, can be used. At this depth nappage is frequently described as a ‘bouncing’ technique, with numerous injections 2 cm apart. Pressure on the plunger is applied when the needle is in contact with the skin.
Deep Intradermal Injections
Deep intradermal injections are administrated at 2–3 mm depth with a volume of 0.5 mL per injection.
Hypodermal Injection
These injections can vary between 4 and 13 mm depending on the pathology being treated. For our purposes, the techniques that will be described are:
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nappage at 1 mm for skin rejuvenation (sometimes called mesoglow)
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nappage at 2–3 mm for cellulite
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point-by-point at 13 mm for localized fat (lipodissolve injections usually consist of phosphatidylcholine, and are meant for localized fat elimination)
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‘point by point’ technique, which may be used to minimize scars.
AESTHETIC MESOTHERAPY
Localized Fat
Adipose tissue has two types of receptors, α and β, that normally interact with epinephrine norephinephrine and glucagon. These receptors may be stimulated by a number of medications that will in turn stimulate or suppress lipolysis. It should be noted that receptors are distributed differently in men and women, but in general there is a higher proportion of alpha receptors in the hip and buttock areas and more beta in the mid and upper torso.
Cellulite
Cellulite refers to dimpling of the skin and most commonly affects the thighs and buttocks. Cellulite is brought about by alternating depressions and protrusions in the upper compartment systems of fatty tissue.
There are three major components in cellulite: hypertrophic adipocytes, thickening of connective tissue and consequently, bad drainage of the intercellular liquid.
The pathophysiology may be attributed to a number of factors:
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genetic, gender and hormone factors
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vascular factors, including venous stasis and decreased lymphatic drainage
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lifestyle factors, such as tobacco, weight gain, and lack of exercise.
On a clinical level ( Figs 13.1–13.4 ) the states can be identified as follows.
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Stage I can be elicited by compressing the skin but is otherwise not visible ( Fig. 13.1A & B ).
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Stage II is visible only on standing ( Fig. 13.2 ).
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Stage III is visible on standing or lying down ( Fig. 13.3 ).
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Stage IV is visible on both standing and lying down with moderate to severe nodules or pitting ( Fig. 13.4 ).
Histologically, stages I and II are characterized by venous stasis and edema, and stages III and IV by fibrosis, with the eventual encapsulation of adipocytes by collagen fibers, forming micronodules and macronodules that are easily palpated.
Treatment
Treatment of cellulite can be very frustrating for both physician and patient as it often requires a combination of different modalities and an understanding and commitment from the patient to lifestyle changes.
In stages I and II the main purpose is to to contract the veins, open the capillaries and decrease the edema to avoid fibrosis in the future. After preparation using an appropriate disinfectant it is possible to use either point-by-point injections or nappage if we wish to avoid bruising. Many combinations are used but in general they include:
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pentoxyphylline (Trental®) and/or phentolamine as a capillary dilator
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dihydroxyergotamine to cause vasoconstriction and reduce edema
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a solution of sodium monomethyltrisilanol orthohydroxybenzoate, associated with a derivative of bioavailable organic silicon and salicylic acid (Conjunctyl®) to increase collagen
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procaine, a potent vasodilator.
In Stages III and IV phentolamine is always used for dilation, and for the fibrosis Conjunctyl®, collagenase may be used sparingly with subcision to undermine the fibrous bed of large nodules. Treatments should be weekly for 8 weeks followed by biweekly sessions for 1 month, and then monthly for 2–3 months. Depending on the severity, several other classes of drugs and herbs may be used but we should first briefly discuss the physiology of lipolysis.
Lipolysis
If blood sugar is low or metabolic demands increase, glucagon and epinephrine, respectively, are released. These hormones increase cyclic AMP, which in turn binds to protein kinase and stimulates the lipases. It should be noted that beta-2 receptors increase lipolysis, alpha-2 receptors inhibit it. It is known that if phosphodiesterase is inhibited it will interfere with this process, probably by interfering with the binding of cyclic AMP to protein kinase. Hence inhibiting phosphodiesterase and stimulating the beta receptors (where epinephrine binds) and inhibiting the alpha receptors will all increase lipolysis. Many formulas use these principles.
| DRUG | ACTION |
| Aminophylline, Forskolin, caffeine | Phosphodiesterase inhibitors |
| Isoproterenol | β2 agonists |
| Yohimbe and phentolamine | Block α2 receptors |
| Acetyl-L-carnitine | Increases the transport of free fatty acids into the mitochondrion to be metabolized |
| Artichoke, mellilotus/rutina | Increase lymphatic drainage and decrease venous stasis |
Localized Fat
Two further treatments are used in the treatment of both cellulite and localized fat. The first is a mixture of phosphatidylcholine 50 mg/mL and deoxycholic acid 4.75 mg/mL, known as PC/DC, which has been used to facilitate lipolysis. Since the injections involved, at 13 mm depth, are into the hypodermis rather than the dermis, many consider this treatment not to be a form of mesotherapy and hence refer to it as ‘lipodissolve’. Many practitioners combine PC/DC with the mixture of medication mentioned in the last section for treatment of localized fat and cellulite in Stages III and IV. The technique used is point-by-point PPP, 2 cm apart in the area to be treated. The use of PC/DC will inevitably lead to localized edema, swelling and pain. The pain subsides within 1 day and the swelling within 2–3 days. It is believed that the inflammatory response evoked by the deoxycholic acid causes retraction of the skin after lipolysis. Where a ‘cocktail’ is used, careful monitoring of the total doses of aminophylline, isoproteronal and yohimbe is required because of the associated cardiovascular effect and aminophylline toxicity. Patients with mitral valve prolapse, coronary artery disease (CAD) or known cardiac arrhythmias should not be injected with isoproterenol or yohimbe. According to Patricia Rittes, the use of PC/DC in pure form, undiluted, has avoided many of the complications associated with the use of the β-agonist, aminophylline, and alpha-2 agonists.
Facial Lipodissolve
Patricia Rittes’ protocols involve the use of PC/DC for other localized areas of fat:
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Double chin injections ( Fig. 13.5 ): 0.5 mL of PC/DC in three to four areas and for jowls 0.5–0.6 mL at two points bilaterally.
Fig. 13.5
Post-mesotherapy.
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Fat pockets in the lower eyelids are treated to a depth of 6 mm with two to three injections of 0.1 mL of product per fat pad.
Any area of the body can be treated with lipodissolve: axillary folds, love handles, saddle bags and abdomen. Generally the abdomen is divided into four quadrants with either the lower or upper abdomen being treated with a maximum of 20 mL of PC/DC in each session. The treatment per area is every 2 weeks for four to six sessions. If results are not achieved, the sessions can be repeated after 2 months, as the PC/DC continues to work for up to 10 weeks. One study on love handles showed histological changes that were primarily inflammatory, with lipolysis and release of free fatty acids and phagocytosis at 10 weeks.
Loose Skin
Attempts have been made to treat loose skin with PC/DC, achieving occasional success in the periumbilical area. The fibrosis necrosis that follows injection into small fat pockets around the umbilicus will occasionally cause retraction and tightening of the lower abdomen.
For the face glutathione and DMAE can be applied by nappage to a depth of 2 mm to create a mild lifting of the face.
Mesotherapy has not been effective for the tightening of loose skin on the posterior arms and anterior thighs.
Mesoglow/Mesolift
This procedure, shown in Figure 13.6 , is used for skin rejuvenation and is not intended to replace Botox® or the various injectables. It is meant to improve the quality of the skin, repair sun damage with antioxidants, and to tighten skin and restore its hydration and shine.
