COSMETIC DERMATOLOGY

A primer on cosmetic dermatology—Part II

By Robin Ashinoff, MD

With so many baby boomers seeking the fountain of youth, demand for cosmetic procedures is booming, too. A dermatologist shares her expertise on microdermabrasion, Botox injections, and augmentation with collagen.

Cosmetic dermatology is booming, even expanding into unexpected places like the obstetrician/gynecologist office. In Part I, I discussed the procedures for eliminating spider veins through sclerotherapy, lasers and intense pulsed light, and laser hair removal. In this concluding article, I'll cover microdermabrasion and Botox injections for treating wrinkled foreheads, frown lines, crow's feet, and horizontal lines of the neck. We'll look at soft tissue augmentation using collagen, as well. My goal is to describe the products currently available for these procedures (and those coming soon to the United States), tell how I deal with adverse reactions, and share specifically how I perform Botox injections and soft-tissue augmentation.

Microdermabrasion

Although similar to a superficial chemical peel, microdermabrasion is a rejuvenating manual exfoliation procedure that has become very popular in the US. It can be performed on all skin types with varying amounts of suction and abrasion; most patients find the procedure painless and relaxing. Different machines are able to achieve differing levels of abrasion, but keep in mind that some of the more powerful settings on the stronger of these instruments can cause bleeding and ablation into the papillary dermis. The machines currently available use either aluminum oxide crystals or sodium chloride crystals. The first of these many microdermabrasion units came to the US in 1996 or 1997.¹ Most machines use aluminum oxide crystals with negative pressure systems, whereby crystals pass over the skin and then are simultaneously vacuumed up with negative pressure.

Indications for microdermabrasion include acne, irregular skin texture, mild acne scarring, irregular skin pigment, and perhaps striae. Although there are only a few scientific studies on the usefulness of microdermabrasion, more are entering the literature. Microdermabrasion has been shown to alter the epidermal barrier—increasing skin hydration and decreasing transepidermal water loss—which may be the physiologic explanation for the clinical improvement patients see after a series of treatments.²

We recommend preoperative counseling for patients who have a history of frequent herpetic infections or active viral or bacterial skin infections, and we recommend that those with a strong history of herpetic infection receive prophylactic antiviral therapy, as they may not be good candidates for the procedure. Our practice is to first defat a patient's skin with 70% isopropyl alcohol. The woman is told in advance to avoid wearing contact lenses on the day of the procedure. We cover her hair with a surgical bonnet and her eyes with cloth eye pads—and advise her to keep them closed. As noted, microdermabrasion machines vary in power from aesthetic units that ablate very superficially to those that can penetrate quite deeply. For that reason, when nearing sensitive areas such as the eyes and over bony prominences of the face, the suction and abrasive settings should obviously be lowered.

We also fully instruct women about sun protection and precautions, telling them not to use any irritating medications—including retinoids or irritating acne medications—for at least 2 to 3 days after a microdermabrasion session. We further advise patients that multiple sessions, approximately every 2 weeks, are needed for the best improvement. Usually we recommend a series of six treatments and then monthly ones thereafter.

It's extremely rare for microdermabrasion to cause complications. At times, women may get prolonged erythema for 1 or 2 days, or even purpura from too much suction in certain areas. Although postinflammatory hyperpigmentation may occur, in practice we find it quite rare. Patients do report that their skin is "smoother" and that friends have commented on how "refreshed" they look. Certainly the temporary effect of inducing posttreatment edema may contribute to the skin enhancement. Studies have shown that following microdermabrasion there is some laying down of new collagen in the upper papillary dermis.³ Microdermabrasion is sometimes combined with nonablative laser resurfacing to enhance the results of both procedures.

Botulinum toxin

Botulinum toxin is a purified protein toxin produced by the bacterium Clostridium botulinum. Despite being one of the most lethal toxins known to mankind, it's been used in neurology and ophthalmology for many years to treat muscular spasms, blepharospasm, and strabismus.⁴ Recently it was approved by the FDA for cosmetic use. Of the eight different subtypes of toxins produced by C botulinum—A, B, C, (C₁, C₂) D, E, F, and G—one of these, C_2, is a vascular permeability toxin. The rest are neurotoxins. Botulinum toxin A Botox, (Allergan, Calif.) and "Myobloc" (Elan Pharmaceuticals, South San Francisco, Calif.) botulinum toxin B are not interchangeable. (Specifically, one unit of Botox equals 50 to 100 units of Myobloc).

Botulinum toxin works by binding irreversibly to the presynaptic neuron, which is then brought inside the cell through receptor-mediated endocytosis; a complex is then formed that is responsible for blocking the release of acetylcholine from the cell membrane.

"Botox" and "Myobloc" are available in different preparations. Botox comes in vials of 100 units frozen and must be reconstituted with nonpreserved saline, and theoretically used within 4 hours. However, studies have shown that Botox is still very effective and safe even at 1 month if kept refrigerated after reconstitution.⁵ Myobloc is provided in liquid form in vials of 2,500, 5,000, and 10,000 units. It remains stable for 2 years when stored at a temperature between 4° to 8°C. At present, the dosing of Myobloc for cosmetic use is still being determined, as it is only approved for cervical dystonia.

In general, developing resistance to Botox has not been a problem in patients treated for cosmetic purposes or even when used for treating hyperhidrosis (excessive perspiration). It is extremely useful for the latter—but in much larger doses. Antibodies that can neutralize the protein have been reported in 3% to 5% of patients treated for cervical dystonia with Botox, but these patients also receive much larger doses than we give for cosmetic use. Since botulinum toxin produces a defect at the neuromuscular transmission level, treatment is relatively contraindicated in women with myasthenia gravis or those on aminoglycosides, which impair neuromuscular transmission. Cosmetic uses of Botox include treatment for the horizontal lines of the forehead, glabella, frown lines, crow's feet, as well as for the horizontal neck lines and other areas on the lower face.^6-9 Injecting botulinum toxin below the zygomatic arch, however, can be fraught with greater complications, including inability to smile on that side, asymmetry, drooping, and drooling.¹⁰ Our office practice is generally to stay above the zygomatic arch on the face. Again, Botox has been shown effective also in treating hyperhidrosis of the axillae, hands, and feet. Even though as much as 100 to 200 units per treatment are usually necessary, results can last for more than 6 months. Because injections in the hands and feet can be quite painful, regional blocks are necessary, and patients can experience muscle weakness following these injections.

Until recently, botulinum toxin for cosmetic use was off label, but I have used Botox for more than 4 years, off label, with excellent results and have encountered few side-effects (see "Injecting Botox: How is it done?".) Now that the FDA has approved it for cosmetic use, the package insert recommends 2.5 mL of nonpreserved saline for reconstitution. Botox has also been used to treat migraines, achalasia, dysphonia, cervical dystonia, cerebral palsy, and chronic anal fissures. To date, studies comparing Myobloc and Botox have shown that Myobloc can be quite effective. Its onset of action seems to be slightly more rapid than Botox, but it may not last as long.

Injecting Botox: How is it done?

A wide range of dosing has been prescribed for Botox. Some clinicians prefer to use electromyelography (EMG) guidance to locate the part of the muscle most active when a patient grimaces or smiles and to inject "hills" formed by the patient's rhytides (wrinkles) when he or she maneuvers. After a while, you get a feel for precisely where to inject the Botox. I started out several years ago with an EMG machine and used it for guidance. We always advise patients that the Botox usually lasts about 4 months, but we have seen it last shorter and longer periods of time. Because men tend to require larger doses due to their larger muscle mass, their rhytides may or may not resolve completely. Complete resolution is unlikely if the line to be eliminated is fixed in the skin at rest—that will take many more months of prolonged treatment.

We also tell patients not to take any aspirin or aspirin-like products, as these might cause bruising following the treatment. We use a topical anesthetic before the treatment and ice packs before and after to minimize bruising and to provide anesthesia. Before injecting, it's essential to be familiar with the muscles governing facial expression, including the location of the frontalis, corrugator supercillii, orbicularis oculi, and the procerus muscles of the face.

For crow's feet, we usually inject about 12 to 15 units of Botox on each side of the lateral canthus, injecting the area about 1.5 cm outside the lateral canthus, over the zygomatic arch. We use nearly double that amount—25 to 30 units—for glabella folds and wrinkles of the middle forehead (Figures 1 and 2). Many times, if patients have horizontal forehead lines, we'll inject 2 to 4 units at varying areas of the frontalis. Botox will spread for about 1 to 1.5 cm around the injection site. Therefore, we advise patients not to lie down for 3 hours after injection, especially when it's injected into the forehead, so that the Botox does not drift into the levator muscles and cause blurred vision or the upper eyelid to droop (ptosis).¹⁰ If ptosis—which can continue for several weeks—does occur, any of the following alpha-adrenergic agonists can be used as mydriatic agents: Iopidine 0.5% (Apraclonidine, Alcon Labs, Ft. Worth, Tex.), ophthalmic eyedrops, and also Neosynephrine hydrochloride 2.5% (Phenylephrine, Sanofi Winthrop Pharmaceuticals, New York, N.Y.). These remedies work by causing contraction of Muller's muscle (which is situated beneath the levator muscle of the upper eyelids) and will elevate the lash margin 1 to 2 mm, which is usually enough to make the woman's eyelids symmetrical again.^5,6 The agent can be repeated as necessary until the ptosis disappears.

A conservative approach is necessary to avoid drooping eyelids when treating older patients, who may have a reduced or absent orbital septum. Again, we also encourage patients to remain upright and to avoid lying down or any muscle manipulation for the first 3 to 4 hours to minimize the potential for diffusion. During and for the first hour or 1 ¹/₂ hours following the procedure, we encourage women to actively contract the muscles that we're trying to relax, to ensure maximum uptake of the Botox at the neuromuscular junction. Patients are forewarned of the possibility of asymmetry initially, which would then be later corrected.¹⁰

Double vision (diplopia) is another possible side effect of Botox that can happen if the drug should migrate and paralyze the lateral rectus muscle. Botox has been used effectively to relax platysmal bands on the neck, in the infraocular area to give a wider-eyed appearance, as well as in the chin and lower face, although these latter two sites may have a greater complication rate. When used in the forehead, it can also contribute to a nonsurgical brow lift by lifting up the eyebrow.¹²

Botox has been a wonderful addition to our cosmetic armamentarium and if used correctly can quite effectively reduce wrinkles to patients' great satisfaction.

Soft-tissue augmentation

Because the world of filler substances has undergone a small revolution over the last few years, many more substances are now—or soon will be—available for soft tissue augmentation (Table 1). These include bovine collagen (the first substance to become available for cosmetic soft-tissue augmentation more than 20 years ago), the patient's own collagen, and materials like hyaluronic acid that are not yet approved in the US. Unfortunately, no one ideal filler substance exists that has no risk of allergic reaction, is long-lasting or permanent, painless and easy to inject, and inexpensive.

TABLE 1
Commonly used filler agents

Bovine collagen. Approved by the FDA in 1981, this consists of 95% type I and 5% type III colla-gen (McGhan Medical, Fremont, Calif.). Zyderm I was the first material available in a concentration of 35 mg/mL in a phosphate-buffered saline solution with 0.3% lidocaine added for anesthesia. Zyderm II is twice as concentrated at 65 mg/mL in a phosphate-buffered saline solution with 0.3% lidocaine added. Zyplast is 65 mg/mL in concentration and contains cross-linked collagen by the addition of glutaraldehyde. Of the three, Zyplast is least likely to cause allergy and resists bacterial collagenase. Because it lasts longer in the skin, it is used to fill deeper defects. Studies of these substances have revealed that they disappear histologically after 6 to 9 months.¹¹

Some 3% to 3.5% of the population will have a hypersensitivity reaction to collagen when tested. Of those patients whose first skin test is negative, 1% to 5% will still get an allergic reaction if collagen is injected a second time. For this reason, the standard technique now involves two skin tests done anywhere from 2 weeks to 1 month apart so that the time between the first skin test and injection into the face is approximately 6 weeks. By documenting two negative skin tests, you can decrease the rate of allergic reaction to collagen to less than 1%.^12,13 The practice at our office for a patient who has not been treated or has not had a skin test within 12 months is to do a skin test to reduce the possibility of an allergic reaction. If the woman does develop an allergic reaction, it usually resolves within 4 to 6 months; it can, however, last up to 2 years. (One of my patients had a reaction that lasted for 10 months.) A skin test provided by the company consists of 0.1 mL of Zyderm I and is usually evaluated after 72 hours and after 1 month.

Bovine collagen can cause both allergic and nonallergic adverse reactions. Temporary side effects, of course, include bruising, reactivation of herpes, and rarely bacterial infection. If a patient has a history of herpetic simplex infection and we are going to inject around the mouth, I give prophylactic antiviral therapy. Sterile abscess formation may be an atypical form of allergic reaction which is seen more frequently with Zyplast.¹⁴ The drug should not be injected into the glabellar region because this can cause necrosis of the overlying skin and subsequent scarring—possibly due to either intra-arteriolar injection or compression of vessels. Intra-arteriolar injection is also thought to have caused several cases of unilateral blindness resulting from retinal artery occlusion.

Once a person develops an allergic reaction to bovine collagen, it usually presents with swelling and erythema (often intermittent) at the site of injection. Although topical and intralesional corticosteroids can be used to manage these patients, once the treatment is stopped the allergic reaction flares up again. Antihistamines and nonsteroidal anti-inflammatory drugs (NSAID) have also been used with poor results, as have oral corticosteroids. Bovine collagen is best used in the nasolabial, perioral, and glabella areas (see "My procedure for soft tissue augmentation".)

My procedure for soft-tissue augmentation

Human collagen. Autologen (Collagenesis Inc., Beverly, Mass.) uses the patient's own collagen derived from a large piece of tissue, as obtained in an abdominoplasty (from abdomen tightening) or rhytidectomy. For patients who wish to use their own tissue at a later date, it can be stored up to 5 years and banked by the company. In addition to giving patients the option to store tissue, an advantage of Autologen is that no skin test is necessary. The disadvantages, however, include processing delays, high cost, pain, and the need for a very large piece of tissue.¹³

Promising fillers on the horizon. A host of other materials now available only outside the US may become available here in America within the next few years. Of these, the hyaluronic acid derivatives are the most promising.^15-17 Hyaluronic acid, a mammalian polysaccharide found naturally in our dermis, has the ability to bind water, which increases skin hydration and plumps up the skin. In one study using Hylan B gel on 150 patients, at week 12, 84% of patients showed moderate improvement and 80% reported moderate or even better satisfaction.¹⁶ Adverse reactions in these patients (who'd received injections for wrinkles or scars) were limited to erythema and bruising. The staying power of Hylan B gel was also compared with bovine collagen in guinea pigs. At week 26, histologically gel was still present at 87% of the sites compared to the presence of collagen in only 25% of the bovine collagen group.¹⁵

Hyalform gel (BioMatrix, Inc., Ridgefield, N.J.) has a concentration of 6 mg/mL of hyaluronic acid. Derived from rooster combs, it is already available in the US for injection for osteoarthritis of the knee. Another material, Restylane (QMed, Uppsala, Sweden), which is derived from a bacterial fermentation product, is more concentrated at 20 mg/mL. It is biocompatible and biodegradable. Because hyaluronic acid is not species specific, no skin test is required and it may last longer than bovine collagen. Neither product contains anesthesia, and therefore a topical or a regional nerve block anesthesia is usually necessary.

Because hyaluronic acid is found in the ground substance of our tissue, it absorbs water and can expand. Therefore, the less concentrated the product is, the more water it may bind to give the impression of a more long-lasting correction. An advantage of these preparations over bovine collagen is that they do not require refrigeration and can be stored for at least 1 year at room temperature. I've been fortunate to have used one of these products (Restylane) in patients and almost every one of them was very happy with its performance. When hyaluronic acid becomes available in the US, many physicians doing soft-tissue augmentation will certainly use it widely—as is already the case in Europe, Canada, Australia, and South America, where it is very popular for lip augmentation. Another advantage of Restylane is that it comes in three varieties. Perlane is for deeper rhytides and Restylane-Fine for more superficial wrinkles, such as those around the eye.^13,15,16

Recently, an FDA Advisory Panel recommended approval of Artecoll (Rofil Medical International B.V, Breda, The Netherlands), another substance used in Europe as a filler. It is composed of polymethylmethacrylate microspheres (PMMA) suspended in a 3.5% solution of collagen.¹⁵ PMMA is commonly known as Plexiglas or Lucite. When the collagen dissipates, the microspheres cause a fiberblastic reaction, which contributes to long-term improvement. Certainly, as with bovine collagen, allergic reactions can occur. Dr. Arnold Klein, an expert in skin augmentation, believes it is not really what material you inject that is the most important criterion for improvement of rhytides or depressions in the skin, it is really the expertise you attain in learning to use it, so becoming very competent in using one or two materials will yield the best results.¹⁵

Conclusions

Cosmetic dermatologic procedures can be very rewarding for the physician as well as for the cosmetic patient. However, cosmetic patients especially have different expectations than those seeking medically necessary treatment and need additional time and explanations of the potential risks and benefits of the procedures discussed within this review. Physicians performing these procedures not only need expertise in the performance of the procedure, but just as importantly in how to deal with any possible complications. Once mastered, these ambulatory procedures can greatly enhance a patient's outlook and self-esteem.

Key points

REFERENCES:

1. Tsai RY, Wang CN, Chan HL. Aluminum oxide crystal microdermabrasion. A new technique for treating facial scarring. Dermatol Surg. 1995;21:539-542.

2. Rajan P, Grimes PE. Skin barrier changes induced by aluminum oxide and sodium chloride microdermabrasion. Dermatol Surg. 2002;28:390-393.

3. Shim EK, Barnett ED, Hughes K, et al. Microdermabrasion: a clinical and histopathologic study. Dermatol Surg. 2001;27:524-530.

4. Carruthers A, Carruthers J. Cosmetic uses of botulinum A exotoxin. Adv Dermatol. 1997;12:325-347.

5. Garcia A, Fulton JE Jr. Cosmetic denervation of the muscles of facial expression with botulinum toxin. A dose-response study. Dermatol Surg. 1996;22:39-43.

6 Carruthers A, Carruthers J. Botulinum toxin type A: history and current cosmetic use in the upper face. Semin Cutan Med Surg. 2001;20:71-84.

7. Carruthers JD, Carruthers JA. Treatment of glabellar frown lines with C. botulinum-A exotoxin. J Dermatol Surg Oncol. 1992;18:17-21.

8. Huilgol SC, Carruthers A, Carruthers JD. Raising eyebrows with botulinum toxin. Dermatol Surg. 1999;25:373-376.

9. Carruthers JA, Lowe NJ, Menter MA, et al. A multicenter, double-blind, randomized, placebo-controlled study of the efficacy and safety of botulinum toxin type A in the treatment of glabellar lines. J Am Acad Dermatol. 2002;46:840-849.

10. Klein AW. Complications and adverse reactions with the use of botulinum toxin. Semin Cutan Med Surg. 2001;20:109-120.

11. Stegman SJ, Tromovitch TA, Glogau RG. Injectable collagen. In: Cosmetic Dermatologic Surgery. 2nd ed. Chicago, Ill: Year Book Medical Publishers, Inc; 1988:131-149

12. Klein AW. Indications and implantation techniques for the various formulations of injectable collagen. J Dermatol Surg Oncol. 1988;14:27-30.

13. Ashinoff R. Overview: soft tissue augmentation. Clin Plast Surg. 2000;27:479-487.

14. Hanke CW, Higley HR, Jolivette DM, et al. Abscess formation and local necrosis after treatment with Zyderm or Zyplast collagen implant. J Am Acad Dermatol. 1991;25:319-326.

15. Klein AW. New filling substances on the horizon. In: Narins RS, ed. Cosmetic Surgery: An interdisciplinary Approach. New York, NY: Marcel Dekker; 2001:313-331.

16. Piacquadio D. Crosslinked hyaluronic acid (hylan gel) as a soft tissue augmentation material: a preliminary assessment. In: Elson ML, ed. Evaluation and Treatment of the Aging Face. New York, NY: Springer-Verlag; 1994:304-308.

17. Piacquadio D, Jarcho M, Goltz R. Evaluation of hylan B gel as a soft-tissue augmentation implant material. J Am Acad Dermatol. 1997;36:544-549.

Dr. Ashinoff is Chief, Dermatologic and Laser Surgery, New York University Medical Center, Ronald O. Perelman Department of Dermatology, and Associate Professor of Clinical Dermatology, New York, N.Y.

Robin Ashinoff. A primer on cosmetic dermatology-Part II.

Contemporary Ob/Gyn

Apr. 1, 2003;48:100-115.