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"As a result, chemical muscle relaxation—which uses microdoses of botulinum toxin—will take off and gain popularity."
In 1990, in Canada, Dr. Jean Carruthers, an ophthalmic surgeon in Vancouver, regularly treats patients with blepharospasm, or eyelid spasms, using precisely targeted injections into the muscles around the eyes. She repeatedly observes the disappearance of wrinkles in the glabella, the area between the eyebrows.
Together with her husband, dermatologist Dr. Alastair Carruthers, she begins a clinical study that will last five years. They present their findings at the 1992 American Academy of Dermatology (AAD) meeting in San Francisco. I believe I am the only French physician attending that session, and I admit that my reaction mirrors that of many of my American colleagues: I am astonished that anyone would dare treat forehead wrinkles with such a toxin! It must be said that merely mentioning it is frightening. I therefore quickly put the presentation out of my mind. I will come to regret it.
In 1897, the bacterium responsible for producing a highly potent neurotoxic protein is isolated: Clostridium botulinum. This bacterium, originally called Bacillus botulinum, is found in certain spoiled canned foods and soils. Foodborne intoxication causes flaccid paralysis of skeletal muscles and can lead to death, particularly through asphyxiation.
In the 1970s, drawing on the muscle-relaxing properties of type A toxin, Alan Scott, an ophthalmologist in San Francisco, publishes the first study on its use to treat diplopia, followed by childhood strabismus. This marks the beginning of therapeutic applications of botulinum toxin, primarily in ophthalmology.
From 1978 onward, botulinum toxin injections extend beyond ocular disorders to the treatment of abnormal facial movements. In 1988, neurologist Marie-Hélène Marion introduces the treatment in France for dystonic disorders, including blepharospasm, oromandibular dystonia, spasmodic torticollis, and writer’s cramp.
In France, a plastic surgeon’s initiative sparks interest in the toxin. Some time after the landmark 1992 meeting, Dr. Patrick Klap, an otolaryngologist, confirms to Dr. Benjamin Ascher that he, too, has observed wrinkles disappearing in patients treated for facial paralysis.
As I regularly perform liposuction at Dr. Ascher’s clinic, he brings up this medical toxin again, which I had put out of my mind and whose remarkable efficacy he has witnessed in the United States. He then sets out to obtain official authorization to conduct a clinical study involving both his patients and mine. The results are striking.
On October 22, 1993, he presents a study on toxin injections for forehead wrinkles at the annual meeting of the French Society of Plastic Surgery in Paris. Many colleagues question the approach: surely a surgeon should focus on surgery! But Ascher persists. Together with Patrick Klap, Marie-Hélène Marion, and Françoise Chanteloub, he publishes in September 1994 in the Journal de Médecine Esthétique et de Chirurgie Dermatologique (Vol. XXI, No. 83), followed in February 1995 by a publication in the Annales de Chirurgie Plastique Esthétique (Vol. 40, No. 1): “Botulinum Toxin in the Treatment of Forehead, Glabellar, and Periorbital Wrinkles: A Preliminary Study.” The study includes 19 female patients followed for 12 to 24 months.
In September 1996, B. Ascher publishes again in the Journal de Médecine Esthétique et de Chirurgie Dermatologique (Vol. XXIII, No. 91), reporting a four-year study involving 158 patients aged 30 to 64. Several are my own patients, whom I accompany personally. Alongside him, I therefore have the longest experience with this application in France.
In 1998, he presents botulinum toxin at the International Master Course on Ageing Skin.
As early as November 1997, Top Santé magazine publishes a feature by Linh Pham and Yasmine Bourassé entitled “The Best Techniques for Looking Young and Beautiful,” which asks: “Have you heard of botulinum toxin?”
Impressed by the favorable results and absence of complications, I persuade B. Ascher to train 12 expert physicians and dermatologists in this new technique. They already have substantial experience in aesthetic medicine and belong to my association, GRAME, the Research and Application Group for Aesthetic Medicine. In any event, without intervention, errors resolve on their own within a few months, without sequelae.
This is how chemical muscle relaxation using microdoses of botulinum toxin begins to develop and gain popularity.
Two competing products soon emerge: Botox*, from the U.S. company Allergan, containing 100 units of onabotulinumtoxinA, which receives FDA approval in 2002 for glabellar treatment; and Dysport*, containing 500 units of abobotulinumtoxinA, from the French-British company Ipsen-Beaufour.
In France, the authorities wish to distinguish therapeutic treatment from aesthetic indications. In 2003, Afssaps grants marketing authorization for Vistabel*, containing 50 Botox units, for aesthetic use limited to glabellar lines between the eyebrows. In 2009, Azzalure*, containing 125 Dysport units, also receives authorization, with one Botox unit corresponding to approximately 2.5 to 3 Dysport units.
These two products, authorized for aesthetic indications, may be supplied only by community pharmacies or certain pharmaceutical establishments specified in Article R.5124-2 of the French Public Health Code.
In 2013, marketing authorization is extended to crow’s feet. Treatment of other areas outside the authorized indications remains entirely the practitioner’s responsibility.
The following products become restricted to hospital use: Botox*, Dysport*, Neurobloc*, and Xeomin*, containing incobotulinumtoxinA equivalent to 100 Botox units, from the German company Merz. The latter is subsequently marketed in a 50-unit presentation as Bocouture*. In 2023, they are joined by Letybo*, from Croma.
Azuliance*, the liquid formulation of Azzalure*, has recently become available. It is ready to use and does not require reconstitution with normal saline. Type E toxins, whether recombinant (Ipsen) or native (Allergan/Bonti), take effect within only a few hours, although their duration of action appears shorter.
Other toxins are emerging from different bacterial strains, with claims of a longer duration of action, almost six months guaranteed! One example is Relfydess*, from Galderma, which is also ready to use and requires no reconstitution.
The growing number of competing toxins may eventually lower product prices. Other types of muscle modulators are beginning to compete with botulinum toxin, such as Daxxify*, a peptide-based neuromodulator and the first of its kind on the U.S. market, free of human blood proteins, including serum albumin, and animal-derived ingredients. Its effects are reported to last six months without touch-ups, with fewer adverse effects.
Finally, we should not overlook a competing and rapidly evolving approach: mechanical myomodulation, which acts through volumetric support of the muscles and distension of their microfibrils.
Although eight different types exist, type A toxin is routinely used for both therapeutic and aesthetic indications at extremely low doses that are not life-threatening.
Used medically as a muscle relaxant, botulinum toxin type A competes with acetylcholine, a small molecule that transmits signals from nerves to muscles and also to sweat glands. By blocking this molecule at the motor end plates, where nerve endings contact muscular acetylcholine receptors, the toxin inhibits muscle contraction. There is never paralysis in the strict sense, since the muscle can still be stimulated by an electrical impulse.
Depending on the dose administered, receptor saturation and the degree of inhibition vary. The number of units must therefore be carefully adjusted to achieve the desired effect, using small intramuscular injections directed at the specific facial muscles to be relaxed.
Broadly speaking, the muscles of facial expression contract in opposing directions, through agonist and antagonist muscle groups. The close connections between skin and muscle through the superficial musculoaponeurotic system (SMAS) allow the full range of facial expressions. At rest, these muscles balance one another.
This muscular balance makes it possible to favor one muscle group by relaxing its antagonists through targeted injections of a few toxin units. For example, relaxing the depressor muscles of the lower face, which are partly responsible for marionette folds, favors the action of the elevator muscles, including the zygomatic muscles.
Most of these toxins require an uninterrupted cold chain, with the exception of certain newer products such as Bocouture*. A study conducted at the Geneva cantonal hospitals showed that, once reconstituted, toxin vials remain sterile and retain reasonable efficacy for up to eight days when refrigerated, under the practitioner’s responsibility, provided a new withdrawal needle is used each time (J Med Esth et Chir Derm. Vol. XXXXV, No. 177, March 2018, pp. 15–18).
Since the treatment of blepharospasm, it has been recognized that relaxing muscles with excessive resting tone can be beneficial. This excessive tone produces abnormal or exaggerated contraction at rest and promotes expression lines that tend to become permanent.
This is particularly relevant to horizontal forehead lines involving the frontalis muscle, glabellar lines between the eyebrows involving the corrugator and procerus muscles, and crow’s feet at the outer corners of the eyes involving the orbicularis oculi muscles.
Beyond these three principal authorized indications, other technically delicate facial applications have gradually developed: wrinkles around the eyelids in the orbicularis oculi region; the nasal region, including bunny lines and the nasal tip; wrinkles involving the orbicularis oris; correction of a gummy smile; reduction of depressor muscle tone in the lower face and neck; and reduction of masseter hypertrophy to refine the facial contour.
Other body regions may also be treated, including the calves and pectoralis major muscles.
Another particularly interesting off-label therapeutic indication has developed within stomatology and maxillofacial surgery departments, including those at Georges Pompidou European Hospital and Pitié-Salpêtrière Hospital: the treatment of bruxism and temporomandibular joint pain-dysfunction syndrome.
A study of 1,150 cases published by Luc Chikhani, Jacques Dichamp, Francis Guilbert, and Jacques-Charles Bertrand reports complete pain relief in 64% of cases, improved mouth opening, and correction of masseter and/or temporalis hypertrophy, with cosmetic improvement in facial contours. Bruxism is eliminated in 53% of cases and reduced in 22% of the remaining cases. Comfort during chewing improves in 73% of treated cases, with sustained therapeutic effects.
Another indication related to patient comfort has led to effective treatment protocols: excessive sweating, or hyperhidrosis, of the palms and axillae.
Beyond oculomotor disorders, applications include torticollis and cervical dystonia, hypersalivation and drooling, compartment syndrome, certain gastrointestinal and urologic conditions, and even migraine, which is often relieved.
This treatment is currently growing at 8.8% annually, with 20 million people treated worldwide each year. It is the world’s second most common aesthetic treatment after injectable fillers, except in the United States, where it remains the leading treatment.
Europe is the third-largest market, behind the United States and Asia. China has its own toxin for its domestic market, which is unreliable, while Korea exports highly reliable products: Neuronox*, Botulax*, and Natoba*.
A parallel market involving counterfeit products, illegal injections, and dangerous injections is developing, particularly in Asia but also online.
In France, approximately 100,000 people receive injections annually for aesthetic indications. Patient satisfaction is evolving. Although increasingly younger women are turning to the treatment, often preventively, some women in their thirties no longer want a smooth forehead or to be labeled “Botoxed”: they wish to retain a “natural” forehead.
There is an irrational fear surrounding botulinum toxin. It should be noted that many “poisons” are used in medicine at extremely low doses. One example is digitalin, extracted from the foxglove plant and used to treat heart failure.
Produced in large quantities, the toxin could theoretically be used as a biological weapon. Fortunately, however, it is difficult to handle because it is highly fragile, being particularly sensitive to heat, or thermolabile, and to oxygen in the air.
One incident raised concerns about its possible use for terrorism. In Germany, police found numerous botulinum toxin vials in a hideout used by the Baader-Meinhof group. The authorities classified the product as a potential terrorist weapon, prompting France to do the same. French authorities subsequently became extremely cautious about its medical use.
In reality, as discussed above, the toxin is highly fragile and becomes neutralized upon contact with air, making it difficult to see how it could be used for terrorism.
A few unfortunate incidents in the United States also initially caused concern. A reckless physician with no training somehow obtained a highly concentrated “industrial” toxin and injected his wife and several patients, all of whom developed botulism and died!
Another American dermatologist injected the neck muscles of a well-known actress to relax her platysmal bands. She filed a complaint because she could no longer hold her head upright! Fortunately, the effect resolved after a few months.
In 2007, the European Medicines Agency (EMEA) decided to strengthen precautions for use and expand the list of adverse effects associated with this medication. An Afssaps pharmacovigilance notice dated June 2007 likewise reiterated the risk of serious adverse effects caused by the spread of botulinum toxin.
This partly explains why, until 2003, botulinum toxin products were used in France only for therapeutic purposes, to treat neuromuscular dysfunction. Aesthetic use was off-label and undertaken under the practitioner’s responsibility.
It should nevertheless be noted that no significant, serious, or lasting complication has ever been reported in France in connection with strictly aesthetic use.
It is worth recalling that European treaties allow each sovereign country to determine its own health policy and establish its own healthcare provisions. We certainly experienced the European cacophony during the COVID-19 pandemic!
France frequently chooses to go its own way, invoking what is often an excessive interpretation of the precautionary principle, which can conceal broader political motivations.
In August 1994, an official from the French Directorate-General for Health (DGS) writes to Dr. J. J. Legrand, President of the SFME. Having reviewed the congress program, the official notes that the session entitled “Preliminary Evaluation of Forehead and Glabellar Wrinkle Treatment by Botulinum Toxin Injection” concerns a technique “involving potentially dangerous biological products, outside any legislative or regulatory framework (…) and apparently inconsistent with the interests of public health.”
Clearly, botulinum toxin was frightening at the time! An astonishing article by a professor of neurology in the bulletin of the French Medical Council then causes a scandal, revealing his complete lack of understanding of the subject!
Despite all scientific indicators being favorable, in 2004 the health authorities decide that only physicians qualified in plastic, reconstructive, and aesthetic surgery; dermatology; face and neck surgery; maxillofacial surgery; and ophthalmology may prescribe and inject Vistabel*.
In 2020, two additional specialties are authorized to use the toxin: otolaryngology and head and neck surgery.
General practitioners are effectively prohibited from using BTX, ostensibly to prevent potential diversion or misuse. In reality, this reflects a clear intention to prevent general practitioners from performing aesthetic medical procedures.
Consequently, these physicians, uniquely in Europe, including those with extensive experience, are prosecuted and severely sanctioned if they continue. This occurs particularly through the French Medical Council, normally responsible for validating professional competence, which acts as the government’s enforcement arm regardless of its political affiliation.
I myself was sanctioned for mentioning it on my website, even though, alongside Benjamin Ascher, I was one of the very first physicians to use it and had previously trained hundreds of specialists!
France has truly turned things upside down. Unfortunately, we have become the laughingstock of Europe, despite once priding ourselves on being leaders in aesthetic medicine and surgery.
In some countries, even trained nurses administer the toxin! As for the authorized specialties, even without any specific training, they cannot meet the substantial demand on their own, unless many French dermatologists, already limited in number and overwhelmed with work, set dermatology aside to focus on aesthetics!
What a triumph of public health policy!
For years, the Directorate-General for Health has acknowledged that this is an anomaly and has promised the national union of aesthetic physicians, chaired by Dr. François Turmel, that authorization will be extended to physicians who can demonstrate appropriate training. Yet the decision is repeatedly postponed on purely administrative grounds.
The Directorate-General for Healthcare Provision and the Directorate-General for Health (DGOS/DGS) are still analyzing the permitted scope of practice of aesthetic physicians in Europe and Canada!
Since the new diploma’s curriculum includes BTX, there should be no difficulty amending the marketing authorization. However, we will have to wait for the first graduates, followed by recognition of the prior learning and experience of other experienced physicians!
In healthcare, France moves at a snail’s pace, and physicians are stifled by absurd decisions that border on the ridiculous and contribute to undermining the profession.
By Dr. Fanny POIROT
By Dr. Mélissa Badof
By Dr. Jean-Jacques DEUTSCH
By Jonathan POTIER
By Dr. Alexandre KITIC & le Dr. Sarra CRISTOFARI
By Dr. Fanny POIROT
By Dr. Mélissa Badof
By Dr. Jean-Jacques DEUTSCH
By Jonathan POTIER
