Cosmetic Injectables

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Torunn Sivesind, M.D.

 

Injectable cosmetic products are extremely popular treatment options for individuals seeking an improvement in the signs of facial aging, such as wrinkles, creases, and loss of youthful facial fullness. The types of injectable products available on the market are increasing, as are the approved indications for already-available products. With so many options, choosing the right injectable treatment can seem overwhelming – however, gaining a bit of background knowledge can help immensely in making a smart decision. Broadly speaking, the most commonly used injectable cosmetic products can be divided into two classes: neuromodulators and dermal fillers.

 

Neuromodulators

 

Neuromodulators, such as BOTOX Cosmetic, are preparations of purified botulinum toxin A that has been diluted for treatment. Botulinum toxin is a neurotoxin produced by a type of bacterium, Clostridium botulinum, that causes flaccid (limp, or “floppy”) paralysis. It acts at the neuromuscular junction (the place where nerve and muscle meet) and inhibits the release of acetylcholine from the nerves. Because acetylcholine normally provides the signal for muscles to contract, botulinum toxin prevents muscle contraction and thus leads to paralysis of the affected muscle(s).

 

Clostridium botulinum actually represents a large class of anaerobes (organisms for which oxygen is toxic), and it is divided into groups based on the ability to digest proteins. Four of the groups (I-IV) are capable of producing botulinum toxin, of which there are seven different serotypes (meaning they have different cell surface molecules, or antigens, that are capable of activating an immune response). Clostridium botulinum is responsible for food-borne botulism (usually from canned goods, a result of ingesting pre-formed toxin), infantile botulism (from ingestion of heat-resistant spores, often from honey), and wound botulism. Most botulism outbreaks affecting humans are from groups I (proteolytic) and II (non-proteolytic). Antitoxin therapy is used to treat botulism, along with immune globulin for the treatment of infantile botulism.

 

In the 1980s, botulinum toxin was introduced as a treatment for blepharospasm (eyelid twitch); patients who were treated noticed an unanticipated side benefit: namely, a reduction in the lines around the eyes, or “crow’s feet.” The FDA then reviewed many studies investigating the use of the toxin for wrinkle reduction, particularly for the glabella (the area between the eyebrows, where frown lines appear), and in 2002 approved botulinum toxin for moderate to severe glabellar lines.

 

In both the US and Europe, guidelines outlining the dose and distribution of botulinum toxin injections have been established by expert groups. When these guidelines are followed, and when administered by a provider who has a good understanding of the underlying muscle anatomy, botulinum toxin A is a safe and effective treatment. Most adverse events that occur are due to poor technique. Short-term effects are generally mild, such as headaches and bruising, while long-term effects are more significant, such as drooping of the eyelids (ptosis), which can last weeks or months.

 

 

The beneficial effects of purified botulinum toxin are diverse and impressive, including treatment of chronic migraine headache, hyperhidrosis (excessive sweating), spasmodic dysphagia (difficulty swallowing), esophageal stricture (narrowing), strabismus (crossed eyes), facial wrinkles, overactive bladder, spasticity (stiffness or rigidity of muscles, which can be the result of multiple sclerosis or a stroke), blepharospasm, cervical dystonia (abnormal head position and neck pain), and even the delivery of anti-cancer drugs.

 

The most well-known use of botulinum toxin is for the prevention and treatment of “mobile” wrinkles (those that appear with facial expressions and muscle movement). For this purpose, the toxin is injected directly into the muscles, reducing the muscle actions that lead to the formation of wrinkles and lines between the brows and on the forehead. There are two brands of botulinum toxin available on the market in the US: BOTOX Cosmetic (onabotulinumtoxinA) and Dysport (abobotulinumtoxinA). BOTOX Cosmetic is an FDA-approved product used to temporarily improve the appearance of forehead lines, crow’s feet, and moderate to severe frown lines in patients aged 18-65. It can also provide a lifting effect for the eyebrows. For this purpose, the usual dose is 7-10 units (u) injected into the lateral orbicularis oculi (brow depressor muscles) on each side. To treat glabellar lines, the dose is typically 20 u in five injection sites. For glabellar and forehead lines, the dose is 40 u over 10 injection sites. For crow’s feet, the dose is 24 units in six injection sites. To treat all three areas (forehead, frown, and crow’s feet), the dose is typically 64 units over six injection sites. Dysport is approved only for the treatment of moderate to severe glabellar frown lines in adults 18-65. The dosage of Dysport recommended by the FDA for glabellar lines is up to 50 u divided in five portions. Effects are seen in a couple of days and last three to four months.

 

Neuromodulator Treatment Expectations: Patients can expect to have small mounds (resembling insect bites) at the injection sites, which disappear within about an hour. Bruising is a possibility. Patients should avoid lying down for two to four hours following treatment, and avoid pressure on the treated area for 24 hours. Strenuous exercise can be resumed 24 hours post-treatment. Effects start becoming noticeable at day 3-5, though muscle movement is still possible during this time. Full effect is reached between 7-10 days; sometimes a feeling of heaviness is noticed around this time, most commonly with the frontalis (forehead) muscle. Touch-ups can be performed to adjust the results as needed. BOTOX lasts between three to six months; patients sometimes begin to notice the return of pre-treatment wrinkling after the two-month mark, though generally, maintenance treatments are performed every 3-4 months.

 

Contraindications to botulinum toxin include pregnancy, a history of sensitivity to botulinum toxin, age over 65, and milk allergy (for Dysport only). Blood thinners, muscle relaxers, anticholinergics, and some antibiotics (such as those in the aminoglycoside class), can interact with botulinum toxin and should be discussed with a doctor. Over the counter medications and supplements, including nonsteroidal anti-inflammatory drugs (NSAIDs, such as ibuprofen and naproxen), omega fatty acids and fish oil, among others, can increase bleeding and the risk of bruising with treatment. Rare but serious side effects include muscle weakness, vision changes, and difficultly speaking, swallowing, or breathing – all of which can be caused by weakening of associated muscles. Risk of these events is greatest for those who have pre-existing problems with swallowing, breathing, or speaking.

 

Dermal Fillers

 

Dermal fillers are used to fill and soften the appearance of creases and lines, add fullness and volume to the face, to improve the appearance of shadowed lower eyelids, to augment the lips, to improve the look of recessed scars, and to correct contour deformities. Fillers vary in their degree of firmness or softness, in how long their results last, and in their components. Softer fillers are best for the lips and to smooth fine lines, while firmer fillers are better for volume enhancement of the cheekbones or to fill contour deformities.

 

The scientific basis for the use of dermal fillers can be found in the underlying physical changes responsible for many of the signs of aging: With the natural facial aging process, there is a loss of subcutaneous fat, while the facial skin stretches and exacerbates the drooping or sagging effect caused by loss of volume. The loss of subcutaneous fat also makes facial muscles more visible since there is less “padding” over them, which causes smile lines and other wrinkles to become more noticeable. Most dermal fillers (approximately 90% of those on the market) are preparations of hyaluronic acid (HA). HA is a disaccharide that forms polymer chains, which can be crosslinked. HA is a hydrophilic (water-loving) molecule that holds moisture, plumping and lifting the skin. HA is a naturally occurring component of the human body, found in the dermis, where it is abundantly present; in cartilage and joint fluid, where it provides lubrication; and in ocular fluid.

 

Hyaluronic acid derivatives include the branded products Juvederm Ultra, Juvederm Ultra Plus, Volbella, Voluma, Vollure, Perlane, Restylane, and Belotero. Hyaluronic acid fillers vary in their composition, with the original formulations composed solely of high molecular weight hyaluronic acid. Newer options, such as those with “Vycross” Technology (VT), employ a combination of low molecular weight HA and a smaller proportion of high molecular weight HA. This is meant to yield a more natural or subtle effect for those patients worried about appearing unnatural or overcorrected. VT products are crosslinked to produce a smoother, more moldable product with potentially longer-lasting results. Juvederm Volbella, Vollure, and Voluma utilize VT. Of these, Voluma contains the highest concentration of HA, and Volbella the lowest. Treatment results from Juvederm XC and Juvederm Volbella can last up to one year, Juvederm Vollure lasts up to 18 months, and Voluma may last up to two years. With regular repeat filler treatments, less product may be required with each treatment in order to achieve the desired results.

 

 

Non-hyaluronic acid based dermal fillers include calcium hydroxylapatite and polylactic acid. Calcium hydroxylapatite (Radiesse) is used for moderate to severe creases, including frown lines, marionette lines, and nasolabial folds, and can add volume to the cheeks or areas of muscle wasting. It provides long-lasting results by stimulating the production of natural collagen in the skin, yet also yields instant results by acting as a scaffold to support the skin. Calcium hydroxylapatite is a mineral-like compound that is a naturally-occurring component of bones, though the type used in cosmetic preparations such as Radiesse is synthetically produced. It consists of tiny calcium-based spheres that provide structure to support and lift the skin; by simultaneously stimulating native collagen production, results are enhanced over time and can last a year or more.

 

Polylactic acid (Sculptra) is a synthetic product used to stimulate the body’s production of collagen. It is a non-toxic and biodegradable product that has been used for decades as a suture material. Studies have shown polylactic acid to work especially well in the lower part of the face, where it is used to fill nasolabial folds and laugh lines, and to provide lip augmentation. Polylactic acid does not produce results immediately, because the stimulation of natural collagen synthesis occurs over a period of months. To achieve the best results, the recommended treatment regimen consists of three treatments spaced a month apart. Full results will be seen four to six weeks after the third treatment. Though polylactic acid is thought to be a semi-permanent rather than a temporary treatment, touch-ups may still be needed on occasion.

 

Dermal Filler Treatment Expectations: Immediately following injection, the treated area may appear over-filled or swollen, bruised or red, lumpy or hard, and may be temporarily numb. Application of ice can minimize any associated bruising or swelling. Strenuous exercise should be avoided for 24 hours post-treatment. Rare but serious adverse effects include vascular occlusion and inflammatory reactions. Vascular occlusion is almost always the result of injection into an artery, blocking the blood vessel and impairing blood flow. Occlusion is a complication that can be seen almost immediately — it is suspected when pain and changes in skin color (pallor) occur. Treatment includes dissolving the hyaluronic acid with injection of an enzyme called hyaluronidase, application of warm compresses, and sometimes applying nitroglycerin (a vasodilator) in the form of a 2% paste, though the use of nitroglycerin is controversial.

 

Conclusion

 

While botulinum toxin and the dermal fillers described above represent the vast majority of injectable products used for cosmetic purposes, other options exist for unique indications and particular patient circumstances. These include the use of fat grafting, platelet-rich plasma (PRP), and deoxycholic acid (brand name Kybella), which is used to destroy fat cells in the submental area (below the chin). Ultimately, treatment with any injectable cosmetic product should only be undertaken after careful consideration of one’s goals and expectations, and after discussing the risks and benefits of treatment with a board-certified physician or surgeon.

 

 

 

 

References

 

 

Ahn, M, et al. Temporal brow lift using botulinum toxin A. Plast and Reconstr Surg. 2000 Mar; 105(3):1129-35.

Camargo C, et al. Botulinum toxin for facial wrinkles (Protocol). Cochrane Database Syst Rev. 2014; (9). Art. No.: CD011301. doi: 10.1002/14651858.CD011301

 

Signorini, M, et al. Global aesthetics consensus: avoidance and management of complications from hyaluronic acid fillers-evidence- and opinion-based review and consensus recommendations. Plast Reconstr Surg. 2016 Jun;137(6):961e-71e. doi: 10.1097/PRS.0000000000002184.

 

Tezel, A, Frederickson, G. The science of hyaluronic acid dermal fillers.

J Cosmet Laser Ther. 2008 Mar;10(1):35-42. doi: 10.1080/14764170701774901.

 

Urdiales-Galvez, F, et al. Treatment of soft tissue filler complications: expert consensus recommendations. Aesthetic Plast Surg. 2018; 42(2): 498–510.