Introduction to Botox & Dermal Fillers


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Introduction Aesthetic Medicine and Facial Rejuvenation on the High Street Non-surgical rejuvenation and Aesthetic Medicine are rapidly gaining popularity as society becomes increasingly preoccupied with beauty and the “aesthetic ideal”. On parallel with this demand, our time deficient population are seeking for quick, cost effective treatments with minimal “down-time”. This article concentrates on elucidating injectables commonly used on the High Street. Botox^tm What is it ? Clostridium Botulinum is a rod-shaped bacteria readily found in the soil. BOTOX^tm is derived from Clostridium Botulinum and is also known as Botulinum Toxin Type A. Botulinum toxin was originally developed in 1946 by Dr. Edward Schantz, a young Army officer stationed at Fort Deitrich in Maryland. It was then intended for biological warfare, but since its inception, botulinum toxin has been used therapeutically for more than 20 different disorders, from cerebral palsy to excessive sweating. It was also used then for the treatment of blepharospasm and strabismus. In 1987 an ophthalmologist called Jean Carruthers discovered that one of her patients was requesting ongoing treatments with the drug even after her blepharospasm had stopped. This was because the injections smoothed away the wrinkle between her eye producing a relaxed, untroubled facial expression ! Currently Botulinum toxin is used as a prescription medicine in managing spasticity, dystonia, torticollis, hemifacial spasm, blepharospasm, spastic dysphonia and hyperhydrosis amongst others. Further cosmetic applications have been devised so as to improve the look of forehead lines, glabella worry lines and crows feet amongst others. Injections of botulinum toxin in certain anatomical areas prevent or reduce facial gestures being made. It is these facial gestures which form wrinkles in especially the photo-aged skin. What is of debate is whether Botox should be used for the prevention of wrinkles by having these injections as early in life as possible! It has been cited by many clinicians that with repeated usage of Botox, there is a potential for a prolonged clinical effect with smaller doses ! This essentially means fewer annual visits to see the aesthetician and small amount of Botox used each time ! In the US it is legal to advertise prescription medicines, but in the UK it is illegal to advertise Botox® or any other prescription medicine direct to the general public. Therefore as it currently stands: wrinkle removal with Botox cannot be advertised in the UK. It is interesting to see how clinic websites and patient leaflets have been designed to circumvent such red tape ! Practitioners injecting Botulinum toxin should have valid and current medical indemnity should medico-legal claims arise. To date though, no significant long-term hazards of botulinum toxin injections have been identified. How does it work ? The neurotransmitter acetylcholine is contained in vesicles in the presynaptic membrane which require several proteins (VAMP, SNAP-25 and syntaxin) to mediate fusion with the presynaptic membrane. Injected botulinum toxin binds to the presynaptic membrane and is internalised. The toxin then undergoes cleavage and the individual cleavage products further cleave VAMP, SNAP-25 and syntaxin. Without these necessary proteins for exocytosis at the presynaptic membrane, neuromuscular transmission is brought to a halt, thus resulting in weakness of the injected muscle. The toxin requires 3 to 5 days to see the desired effect. The effect of botulinum toxin lasts from 8 to 12 weeks. Tissue studies have demonstrated no long-term adverse effects of repeated botulinum toxin injections on muscle histological morphology. Cosmetic Indications forehead lines, glabella/frown lines, crow's feet (lateral orbital lines), bunny lines (transverse nasal lines), peri-oral lines (smoker's lines), marionette lines, mentalis dysfunction (chin “dents”), vertical platysma bands, brow lift Contraindications presence of infection at injection sites, pregnancy, breast feeding, hypersensitivity to ingredients used in the formulation, patients taking aminoglycosides (potentiates effect) or any other medication interfering with neuromuscular transmission, patients with a history of neuromuscular weakness eg: Eaton-Lambert syndrome, Myasthenia Gravis Side Effects and Adverse Events Immediate: Haematoma, pain Early: Headaches, diplopia, eyelid ptosis (temporary) Late: Facial Asymmetry, brow ptosis Dermal Fillers What are they ? As we age, we progressively lose dermal collagen and subcutaneous fat. This results in characteristic contour changes in the facial profile and rhytids (wrinkles) forming. Autologous fat has been used as far back in the 19^th century to correct facial contour defects. With modern advances now a large variety of dermal fillers exist as valuable tools in the rejuvenation specialist’s armamentarium. They allow the ability to restore youth by recorrection of profiles, adjust mild asymmetries in profile, improve skin defects and scars without the need to harvest fat. There has been concern previously with bovine collagen which is antigenic and can cause anaphylactic reactions or exaggerated granulomatous tissue responses. Typically a dermal injection of the collagen is injected a week prior to the actual treatment in order to gauge sensitivity to the product. However in some patients, this merely serves to sensitise the immune system and causes an even larger hypersensitive reaction on re-challenging the body with the antigen concerned. Therefore there has been a drift towards using dermal fillers which are not bovine collagen origin. Dermal fillers can be broadly classifiable into either biodegradeable or non-biodegradeable. Biodegradeable fillers can last anywhere from 6 to 12 months, whilst the non-biodegradeable fillers can last between 3 to 5 years. Listed below are some examples of popular fillers used in the high street. This list is by no means exhaustive. Biodegradable Non-biodegradable Hyaluronic acid eg: Restylane, Hydrafill, Artecoll Perlane, Juvederm Evolution Outline New Fill Bovine Collagen Zyderm, Zyplast Autologous tissue: eg: fat Human allografts How does it work ? Wrinkles that appear due to dermal collagen depletion can be treated with appropriate dermal fillers injected into the reticular or papillary dermis. These ‘depressions’ which we call wrinkles are literally ‘filled out’ to a smooth aesthetic contour. New products are available now which can be also injected supraperiosteally in order to give more bulk in required areas allowing fullness in even cheeks and chins ! Indications nasolabial folds, lip augmentation, fine lines, wrinkles and scars eg: acne scarring, perioral lines, fill cheeks / raise cheekbone, reshape the jaw line Contraindications history of an anaphylactic event of any cause, previous sensitivity to bovine collagen, lidocaine sensitivity, pregnancy, active infection at the treatment site, history of keloids, history of atrophic skin diseases, patients with thin, flaccid skin because of the risk of permanent surface irregularities. Side Effects and Adverse Events Immediate: bleeding, haematoma, pain, erythema, allergic reaction or anaphylaxis, oedema Early: asymmetry (over or undercorrection), activation of herpes simplex Late: bacterial infection, cystic skin reactions, local skin necrosis, lumpiness of areas injected Isolagen What is it ? The reduction of the number of active fibroblast cells in the dermis with age contributes to the formation of wrinkles. Logically if we added more fibroblast cells to a patient’s dermis, it was postulated that it might be possible to stop these wrinkles from forming. Isolagen^tm is a company which was founded in 1995. It patented its technology in taking a patient’s own fibroblasts and reproducing them in the order of millions. These cells are then re-introduced via injecting into the relevant treatment area identified. This inherently means that the patient’s immune system will not reabsorb or reject them as with foreign material ie: hyaluronic acid, collagen. Therefore there is an automatic reduction of risk of marked hypersensitivity reactions. Unlike dermal fillers such as bovine collagen , Isolagen^tm treatment consists of autologous new active cells which have the potential to keep regenerating collagen. The company goes on further to store retrievable frozen copies of these fibroblasts at a price premium ! Injecting the body with dermal fillers other than autologous cells, can cause the development of increasing titres of antibodies. This can reduce the duration of the desired aesthetic effect. Therefore in the long term, Isolagen^tm claims that the cost of its treatment will be less for the patient, instead of having regular dermal filler therapy. How does it work Isolagen treatment begins with a 3 mm x 7.5 mm elliptical incision of skin taken behind the ear, under a local anaesthetic. This skin tissue is then sent to the Isolagen laboratory where fibroblasts are stimulated to reproduce in the order of tens of millions. After twelve weeks, the cells are sent back to the clinician to inject into the patient. Once the laboratory has copies of the patient’s fibroblasts, there is no need for additional biopsies. 1 to 2 separate injections are common with 4 to 6 weeks in between. After a period of 3 to 6 months, results are observable in terms of reduction in depth of wrinkles, improvement in skin texture and tone. Indications The indications for Isolagen are the same as for dermal fillers with the proviso that the results are not immediately apparent Contraindications There are no contraindications because this is autologous tissue Isolagen recommends that this procedure is not attempted during pregnancy or lactation Side Effects and Adverse Events Immediate: Haematoma Late Skin necrosis (rare) Mesotherapy What is it ? Mesotherapy is a series of microinjections of a cocktail of vitamins, minerals, medications and amino acids into the mesoderm or middle layer of skin to deliver healing or corrective treatment to a specific area of the body. The technique was invented in 1952 by French Physician Dr. Michel Pistor. It has been described as being a treatment for bodysculpturing, cellulite reduction and skin rejuvenation. The procedure was recognized by the French National Academy of Medicine in 1986 How does it work It was discovered that when small amounts of medications were injected into the mesoderm, blood flow increased to the treated areas, dissolving excess fat deposits, improving lymphatic drainage and removing hardened connective tissue. skin. On the average, patients receive 6 to 10 treatments. These treatments should not be closer together than two weeks and there should be no more than 4 to 5 treatments in an area. Examples of ingredients used in Mesotherapy include: vasodilators, non-steroidal anti-inflammatory agents, enzymes or hormones. Specific examples include: Mesocaine, Buflomedil, Caffeine, Procaine, Theophylline, Aminophylline, L-Carnitin, Artichoke One of the commonest injectable is lecithin, which is phosphatidylcholine isoproterenol, a lipolytic agent with stimulates beta adrenergic receptors. It is interesting to know that lecithin is common in human bile and is necessary for the digestion of dietary fat! It is to be noted though that though empiricially results have been recognised, there have been no clinical scientific studies that have been published in the literature to prove that mesotherapy fulfils its claims. Indications fat reduction, cellulite reduction, sagging skin, reduction of wrinkles, tightening and toning of areas treated Contraindications pregnancy, breast feeding, diabetes, bleeding diastheses, history of DVTs, thomboembolic diseases, immunocompromised patients Side Effects and Adverse Events Immediate: Haematoma Late: Skin necrosis (rare), Urticaria Pigmentosa In Summary Aging is a complex process mainly involving volume loss throughout the face. Repetitive muscle action leading to the formation of fold and wrinkles. Aesthetic Medicine is a fast growing specialty and facial rejuvenation attempts to reverse or at best, delay these processes. Products and techniques available on the high street can be used in combination to effectively reshape and rejuvenate the face and neck. This article is to serve as a short introduction for professionals interested in learning some basics of aesthetic medicine. Popular Injectable Facial Rejuvenation Techniques Available on the High Street Botulinum toxin Dermal Fillers Isolagen Mesotherapy References Wollina U, Konrad H. Managing adverse events associated with botulinum toxin type A: a focus on cosmetic procedures. AM J Clin Dermatol. 2005;6(3): 141-150 Rohrich RJ: Mesotherapy: what is it? Does it work ? Plast Reconstr Surg. 2005 Apr 15;115(5):1425 de Maio M: The minimal approach: an innovation in facial cosmetic procedures. Aesthetic Plast Surg. 2004 Sep-Oct;28(5):295-300. Homicz, MR, Watson D: Review of injectable materials for soft tissue augmentation. Facial Plast Surg. 2004 Feb; 20(1): 21-9 Review Flynn TC, Carruthers JA, Carruthers JA, Clark RE. Botulin A toxin (Botox) in the lower eyelid: dose-finding study. Dermatol Surg 2003; 943-50 Lowe NL, Maxwell CA, Lowe P, et al. Hyaluronic acid skin fillers: Adverse reactions and skin testing. J AM Acad Dermatol 2001; 45: 930-3 Klein AW, Elson ML: The history of substances for soft tissue augmentation. Dermatol Surg 2000 Dec; 26(12): 1096-105 Binder WJ, Blitzer A, Brin MF: Treatment of hyperfunctional lines of the face with botulinum toxin A. Dermatol Surg 1998 Nov; 24(11): 1198-205 Carruthers A, Carruthers J: Clinical indications and injection technique for the cosmetic use of botulinum A exotoxin. Dermatol Surg 1998 Nov; 24(11): 1189-94 Wieder JM, Moy RL: Understanding botulinum toxin. Surgical anatomy of the frown, forehead, and periocular region. Dermatol Surg 1998 Nov; 24(11): 1172-4 Millikan LE: The evolution of dermal implants. Cosmetic Dermatology 2001 Dec; 14(12): 27-30