Cosmetic Dermatology – Page 2

Clinical Pearls-Dermal Filler Complications

April 28, 2014

Wm. Philip Werschler, MD

It is important to keep in mind that complications can occur when using dermal fillers in clinical practice…It’s important that you:

Recognize complications and promptly treat them
Not hesitate to see patients in follow-up and refer them if necessary
Are truthful with your patients and stay in close contact with them

What about impending necrosis? Remember that impending necrosis as a proposed MOA and patient’s actions may have an impact on the development of impending necrosis…Dr Werschler provides us with some practice tips:

Educate staff on concept of impending necrosis
Educate and consent patients on risk of necrosis
- “Scabbing, shedding, discoloration and shallow scarring which may result in prolonged healing and/or the need for reconstructive surgery may occur in rare instances”
When patients call and complain of increasing pain, discoloration, headache or other unusual symptoms, instruct staff to have pt. take a NSAID, discontinue cold/ice packs, and come to office for evaluation

Concern of an impending or acute necrosis is a clinical consideration and you should act immediately! Apply a warm compress, nitropaste, confirm NSAID use, and massage as the first step. You should then evaluate the response and consider the use of hyaluronidase and cover with antibiotic, also consider oral corticosteroids. If frank necrosis occurs, utilize HBO2. If necrosis has already occurred, HBO2 speeds tissue repair and healing. Be sure to consult plastic surgery early.

Fillers 2014: New Fillers and New Data

April 7, 2014

Wm. Philip Werschler, MD

In this presentation at MauiDerm 2014, Dr Werschler, a pioneer in the area of toxins and fillers, provided an overview of the fillers currently available on the market along with newer fillers and new data so that we can utilize this information in clinical practice.

A Brief History of Their Time

We started off with collagen, if you wanted a filler, that’s what you got. This is no longer available. At that point in time, we were really focusing on lines and wrinkles. Collagen became products such as Zyplast and Zyderm and was mostly used on lips, crows feet lines, nasolabial folds, and vermillion borders. Then, for many, many years, we had a lull. So, you either did collagen or you didn’t do injectable fillers.Then starting in 2003, the filler market exploded, as you can see from the chart below.

In December, 2003, the US FDA approved Restylane (Hyaluronic Acid), which revolutionized the dermal filler market . With a duration of six plus months, no pre-treatment skin testing, ease of use, room temperature storage and modest cost, there was now a viable product for the emerging, if nascent, dermal filler market.

Radiesse is a novel “next-generation” filler that was approved in 2006 by the FDA for the correction of wrinkles and folds (such as Nasolabial Folds), and for the correction of HIV-associated lipoatrophy. Radiesse is termed a “stimulatory” or “collagen-stimulator” product. This differs from the previous generation “replacement” space occupying materials collagen and hyaluronic acid. With the addition of collagen stimulation, the duration of effect of Radiesse was extended to 9-18 months.

On the same day that Radiesse was approved, the FDA also approved the first and only “permanent” dermal filler, Artefill (collagen + PMMA). Artefill consists of bovine collagen in combination with polymethmethacrylate spheres. As these spheres are non-biodegradable, they represent a permanent placement into the tissue. Well tolerated with an excellent safety profile, Artefill does require pre-treatment skin testing because of the bovine collagen present. Special handling includes refrigeration, and collagen stimulation gradually anchors the PMMA spheres into place typically after 2-3 treatments.

In 2007/2008 Hyaluronic Acid plus lidocaine was FDA approved for the hyaluronic acids, Juvederm, Restylane and Perlane. Similarly, the FDA approved the mixing of lidocaine and Radiesse by the injector at the time of use. These approvals resulted in greater patient comfort during injection and further expanded the dermal filler marketplace. Stabilized Porcine Collagen came onto the market briefly during this time, however due to problems with patient tolerance and complications, the manufacturer withdrew the product and it is no longer available.

In 2009, the FDA approved Sculptra, poly L lactic acid, for aesthetic use (it received FDA approval in 2004 for HIV associated facial lipoatrophy). A pure collagen stimulator, Sculptra, is technically not actually a dermal filler, however; it is best thought of in this category. Sculptra is routinely mixed with lidocaine and sterile water for injection, requires 3-5 injections sessions to gradually grow new collagen leading to the clinical effect developing over a period of three to six months. Duration is a 2+ years effect based on extensive clinical trials and experience.

More recently, an advanced technology hyaluronic acid, Belotero, and an autologous cultured dermal fibroblast (LAVIV) were approved. Laviv, like Sculptra, is technically not a dermal filler but rather a tissue stimulator that up-regulates native collagen production. This process includes harvesting tissue from the patient (post-auricular) and sending it to a processing laboratory that then amplifies the cell count and returns a viable culture for re-injection. The first FDA approved tissue cell culture therapy for aesthetics, Laviv, presents a multitude of intriguing possibilities in the future.

Most recently (2013), we have hyaluronic acid with Vycross technology, known as Voluma.

In order to use fillers, it is important to understand their mechanism of action. There are two primary components of MOA:

Volume Replacement
Collagen Stimulation-either as part of its MOA or its primary MOA

If you use the above approach, collagen and hyaluronic acids have an immediate correction and they do not really have, as a primary mechanism of action, any neocollagenesis effect; therefore, collagen and hyaluronic acids are replacement fillers. PLLA (Sculptra) and LAVIV are bio-stimulatory. And notably, CaHA and PMMA are blends of both MOAs.

How do fillers exert their characteristics?

Fillers are commonly compared by viscosity ,elasticity and cohesivity, the three physical properties that dictate the ability of a filler to provide volume plus lift and the ability to resist becoming separated in tissue. All three of these measurements are made in-vitro, and are surrogate measures for in-vivo activity. Viscosity is the measurement of a material’s ability to resist a force that is applied to it. It relates to the movement of the material in response to force. So, highly viscous materials require more force to move or spread compared to lower viscous materials. A filler with a high viscosity “stays where you put it”, providing a “what you see is what you get” results. Fillers with lower viscosity will have the propensity to be easily spread and splay into surrounding tissues.

You’ll see on the graph above that the products with the greater viscosity are Radiesse and Restylane SubQ (not available in the US). Does this mean that they are better products? Not necessarily, it depends on the tissue characteristics for which you are looking. It means that these products have more of an ability to push back against a force that is applied to them.

Elasticity, measured as G’, is the material’s ability to push back against a force that is applied to it. Fillers with a high G’ will resist the forces placed on it, such as gravity, skin laxity, etc. and will provide greater lift to the overlying tissues. Fillers with a low G’ will not have the capacity to lift well, and; therefore, require larger volumes of material to compensate.

What does this mean clinically? Well, in part it means that some activity of a filler can be predicted by laboratory measurements. It also means that only personal experience can determine which filler you use for any particular indication and patient experience and satisfaction will determine the final choice of product.

These are important concepts to think about. Some products provide soft lifting and some products provide a firm lifting.

Volume Replacement

Hyaluronic Acids (HAs)

Volume replacement is all about HAs today in the marketplace. It is when you inject a product that occupies a space and holds that space until that product is either removed or, in the case of HAs, is degraded through natural enzyme processing.

HAs have a very simple chemical structure and is identical in all species and tissues; thus it is non-immunogenic. It is found in all vertebrates and synthesized by some bacteria. The identical structure of HA from all sources makes it an ideal substance for use as a biomaterial in health and medicine. HAs are highly hydrophilic; therefore, they absorb water, i.e., their principal method of giving a volumizing effect. They are also rapidly metabolized in vivo.

HA was first discovered in 1934 by Meyer and Palmer and was first used therapeutically in 1970. During the 1980s, Biomatrix, Inc. developed second-generation HA derivitives (hylans) through cross-linking (stabilization), and in 1986 the term “hyaluronan” was coined. The increased stabilization increases the ability of the product to do the work that you want it to do. By 1996, we had the first generation of resorbable gels based on hyaluronic acid of animal origin. In 1998, we had the second generation of resorbable gels based on hyaluronic acid of non-animal origin—these were biphasic products. In 2000, the third generation of resorbable gels came about, based on hyaluronic acid of non-animal origin—monodensified, mono-phasic products. And, in 2005, we saw more technological advances with Cohesive Polydensified Matrix technology, allowing for different tissue characteristics.

HAs can be used virtually everywhere for anything and everything and they are the most versatile of all of the filler products. These fillers may be ideal for novice patients because they have an “eraser” (hyaluronidase) that can be injected to make the product dissolve, if so desired for either aesthetic effect or for treatment of complications including necrosis. . This is a unique feature of this category. Remember that while some HAs seems to work better in certain areas, this is based on personal preference.

What’s New?

Voluma XC
Belotero (sort of)
Expressions (kind of)
Corporate acquisitions and news

Vycross Technology

Juvederm Voluma XC is FDA approved HA to correct age-related volume loss in the mid-face. We know that volume loss creates the aging changes. The VYCROSS technology formulation produces highly cross-linked gel, increasing lift, capacity, and duration. The duration of this product is up to two years. Duration claims are always a slippery slope, so be sure to caution your patients.

The pivotal clinical study was a multi-center, single blind, no-treatment control study of 282 subjects (235 in the treatment group/47 control “no treatment”) in fifteen North American sites. The subjects received 20 mg/ml HA volumizing filler for cheek augmentation to correct mid-face volume deficit. There was one treatment plus one optional “touch-up” one month later.

Eligible subjects must have scored an overall Mid-Face Volume Deficit score of greater than three on a six-point scale.

3 = moderate concavity of mid face, tear troughs, mild nasojugal and pre-jowl, mild prominence of bony landmarks and musculature
4 = significant concavity of mid-face, tear troughs, moderate nasojugal and pre-jowl, moderate prominence of bony landmarks and musculature
5 = severe concavity of mid face, tear troughs, severe nasojugal and pre-jowl, moderate prominence of bony landmarks and musculature

The study endpoint looked at the Mid-Face Volume Deficit scale at six months with the primary endpoint being greater than 70 percent responder rate versus control. The primary endpoint was met with an 85.6 percent treatment group response rate.

Subject Rated Duration

6 months = 95.1%

12 months = 80.4%

18 months = 67%

24 months = 53.7%

Physician Rated Duration

6 months = 76.8%

12 months = 64.3%

18 months = 57.9%

24 months = 46%The range of volume used in the study was rather dramatic as it went from 1.2mL to 13.9mL. The median for all three subregion treatment areas (mid-face) was 6.6mL.

VYCROSS technology has opened up the mid-face volumization category for us, as practitioners.

CPM Technology

Belotero is a “cohesive polydensified matrix” hyaluronic acid. CPM technology allows for variable degrees of product/tissue integration. With less homogenous bulk, there is less monochromatic refraction of ambient light. The net clinical result is that the product may be injected more superficially than other HAs without risk of the Rayleigh/Tyndall effect tinting the skin blue.

Expressions

Expressions is a hyaluronic acid filler that is FDA approved for nasal splinting; however, it is not FDA approved for aesthetic use, yet it is heavily marketed to the aesthetic community. Expressions is an HA product that is made with Bacillus Subtilis Fermentation and it comes in a 1.5mL syringe.

New Approaches to Fillers

NeoCollagenesis

Poly-L-Lactic Acid

Through a variety of mechanisms of action, they stimulate fibroblasts to make collagen, making Sculptra more of a tissue stimulator as opposed to a filler, per se.

It is the only approved pure collagen stimulator currently available in the US; therefore, it is considered “stimulatory” and “biodegradable” in classification. PLLA is indicated for the correction of nasolabial folds. Of note, Dermik aesthetics, a division of sanofi-aventis, recently sold the product to Valeant Pharmaceuticals Intl. based in Canada. It takes time and a number of treatments; however, the duration is about two to three years. It is important to remember that it is difficult to establish exact duration of the product because of one’s natural course of aging.

What is the composition of PLLA?

Poly-L-lactic acid
Sodium carboxymethylcellulose (CMC)
Non-pyrogenic mannitol
Sterile water (added) for injection (USP)
Lidocaine (optional—most dermatologists and plastic surgeons add lidocaine for patient comfort)

Sculptra™ is composed of microparticles of PLLA, a biocompatible, biodegradable, synthetic polymer from the alpha-hydroxy-acid family. It is derived from natural components, it is a crystalline, amorphous mixture with microparticles averaging 40 to 63 μm in size. The slow resorption of PLLA after implantation is due to the high molecular weight (140,000 Daltons) of the polymer and the irregular crystalline shape of the microparticles.

Lactic acid can be converted through polymerization to a variety of polymers, including poly-L-lactic acid. Many of these polymers, including polylactic acid, have been used for many years in medical devices and sutures, including absorbable sealants, flow restrictors, fixation systems, suture anchors/absorbable sutures, fixation screws, and tissue regeneration.

Investigator evaluations throughout the study confirmed that improvements in facial appearance with Sculptra^®Aesthetic were achieved in WAS. As this graph shows, improvements from baseline at 25 months proved to be consistent, progressive, and statistically significant at each time point (P<0.001): 100% of patients improved at week 3; 88.7% at month 13; and 86.3% at month 25.

Where is it used?

Poly-L-lactic acid treatment primarily to add volume, and as such is used to thicken dermis and to stimulate collagen growth in the pre-periosteal plane. Placement may include the temporal hollows, across the zygomata, in the mid face, nasolabial folds, labiomental sulcus, prejowl sulcus, mandibular sweep and angle and for genioplasty. Sculptra is not recommended for use in areas of concentric movement such as the lips and eyelids. In terms of adding volume, this is a great way to go. As you become skilled with PLLA, there are a lot of great things that you can do with it over time.

Personalized Dermal Technology

Azficel-T (LaViv) is an interesting, innovative technology to isolate, purify, and regenerate a patient’s own fibroblast cells for re-injection.

Fibroblast cells produce collagen and play key role in the continued health of skin. Collagen provides firmness and structure to the skin and is essential in supporting the dermis. As skin ages, fibroblast cells decrease and the collagen matrix that provide the skin its structure breaks down.

This is a way to restore the equilibrium. LaViv is the first autologous cell therapy for use in aesthetics filed with the FDA. There is strict release testing on each clinical lot to ensure performance and safety including:

Collagen content testing results must achieve specification for each prepped injection, indicating cells are biologically active and produce collagen
Cell suspension must consist of at least 98% fibroblasts prior to release
Cells in suspension must achieve a viability level of at least 85%

Treatment Process

A small cell sample is removed from behind the ear from a small skin punch biopsy with the use of a local anesthetic. A proprietary manufacturing process multiplies the fibroblasts from the sample into tens of millions of new cells in approximately three months. The fibroblasts are tested by quality control and released by quality assurance prior to the shipment. The cells are then frozen for use in potentially multiple treatment sessions. The recommended regimen is three treatment sessions at three to six week intervals. In clinical trials, Azficel-T and placebo was seen by the time of the third treatment. Dr Werschler feels that if you have a patient who doesn’t want a “foreign” substance used for aesthetic purposes, this is a nice alternative to be able to offer as it’s personalized dermal cell technology. Of note, the side effects are minimal, mostly pruritis.

Volume Replacement + NeoCollagenesis

Calcium Hydroxylapatite (CaHa)-Radiesse

CaHA has a biphasic MOA, it is 30 percent calcium particles and 70 percent CMC gel. CaHa is best used for regional facial contouring. Dr Werschler uses this product for structural augmentation, i.e., helping to define the face. Its mechanism of action is to serve as a filler material initially (particles + gel) then provide long-term benefit through natural collagen integration in and around the particles. The result is a long lasting, but not permanent correction augmentation that feels like the patient’s own tissue. Remember with Sculptra, the volume effect comes from neocollagenesis; however, with Radiesse, because it is a biphasic product, you get an immediate corrective effect which then stimulates neocollagenesis at a rate which prolongs the effect clinically that you see; therefore lasting longer.

The advantages of Radiesse include immediate site-specific correction in one to two sessions and strong structural tissue support with no Rayleigh/Tyndall effect. CaHa is malleable up to two weeks and has a long duration of nine to 18 months. No pretreatment testing is required, it is also cost-effective and does not migrate or obscure radiographic studies and it doesn’t ossify in the skin. Radiesse received approval in the United Sates in 2006 for both HIV and aesthetic use and is the only approved biodegradable dual collagen stimulator and replacement filler currently available in the US. When utilizing Radiesse, no skin or allergy testing is needed and there is no special handling. The product is available in 0.3, 0.8 and 1.5 mL and recently approved 3.0 mL syringes through Merz Aesthetics.

Where is it used?

CaHA is used most everywhere; however, it is not recommended to be used in the lips or around the eyes.

PMMA Dermal Filler-ArteFill

ArteFill was approved in the United Sates in 2006 and is the only approved PMMA-enhanced dermal filler currently available in the US. It is indicated for the correction of nasolabial folds. Suneva Medical acquired (ARTES) Artefill in 2009 and is currently manufacturing, selling, and distributing Artefill in the US. Of note, it is currently awaiting FDA approval for acne scars.

ArteFill is a combination of purified bovine collagen plus polymethyl-methacrylate beads. Essentially, you drop the beads into the tissue that are then carried by the bovine collagen that is then rapidly reabsorbed. You see a neocollagenesis effect from the fibroblasts around the PMMA particles that are locked into place so that they do not migrate providing a long-standing correction. You can see from the graph below that the five-year follow-up study demonstrates long-lasting effects.

Conclusions

Injectables are: Facial Shaping Agents

They can enhance natural features
They can rejuvenate fading youth
They can restore aged, facial features
They can even improve natural beauty
Each product has features that result in certain benefits in clinical use
They are not all alike!

What’s new?

Not that much…but quite a bit
CPM technology is “back” on market
Valeant owns Medicis, Dermik
FDA approval for Allergan’s Vycross technology mid-face volumizer
Expressions is in the neighborhood
Merz has acquired Neocutis
Allergan has acquired SkinMedica
Valeant (Medicis/Dermik) has Obaji
Merz acquired Anteis (Beletero family-Soft, Basic, Intense)

Additionally, Allergan has clinical trials underway in the United States for Volbella and Volift. A new player, Alphaeon, has products at different states of pre-approval; they have licensed Teoxane (filler and skincare line), they have also licensed a neurotoxin which is not yet on the market and the company plans to expand on lifestyle medicine, focused on wellness, beauty and performance.

Clinical Pearls

Use filling agents appropriate to the requirements of the job
- Lifting tissue requires robust strength, longevity, durability, and safety
- For surface “crinkles” use “thin” or “dilute” products
Not all products are created equal – understand the differences!
- Some products create “soft” volume, others “firm” volume
Some areas are more difficult to correct than others (e.g. lips and tear troughs)
- Create facial filling improvement by starting with low-risk/high-satisfaction areas—utilize a STEP approach
Evaluate and approach filling from a multi-step progression:
- Integrate filling with development of structure and support, progress to volume replacement and refine with contour
Product duration claims are a slippery slope—be careful with those and be conservative with your ranges

MauiDerm News Editor- Judy Seraphine

Botulinum Toxin 2014: Tips, Thoughts, Science, & Different Formulations

March 4, 2014

Joel L. Cohen, MD

In this presentation, Dr Joel Cohen, a leader in aesthetic dermatology, and the Director of AboutSkin Dermatology and DermSurgery in Colorado, provides us with an update on the use of botulinum toxin. Dr Cohen begins the session by reminding us, as Dermatologists, that every day we have an opportunity to blend our modalities, i.e., medical, surgical, and aesthetic in order to provide our patients with the best possible outcomes.

Currently, there are three FDA-approved botulinum toxins type A; these are Botox (Allergan), Dysport (Medicis/Galderma), and Xeomin (Merz). All three products are approved to treat glabellar lines; however, Botox was also recently approved for the treatment of Crow’s feet.

Cox and Finn a decade ago, found that botulinum toxin type A injections have been beneficial for patients who feel that their faces are not communicating their emotions properly, want to delay the outward appearance of aging, and/or patients simply want to look their best. Data also suggest that botulinum toxin type A injections can also affect self-esteem. A 2010 health-outcomes survey (randomized data), conducted by Dayan and colleagues, found that the injection of botulinum toxin type A injections demonstrated improvements in quality of life (QOL) and self-esteem and injection-naïve patients demonstrated greater improvements in QOL and self-esteem versus those who had received previous injections.

All three of the FDA-approved products contain a core neurotoxin protein (150 kD BoNT/A), this is where the mechanism of action lies. Botox and Dysport are wrapped in protein, which is part of the neurotoxin complex. Xeomin; however, lacks these accessory proteins. All three products have demonstrated efficacy and have established good safety profiles, but remember that it is difficult to make direct comparisons among the approved botulinum toxins. Keep in mind that the products are different, the dosing can be different, the studies were all designed differently and there are differences among the various study endpoints.

Conversation Ratios

Keep in mind that the three neuromodulators approved for aesthetic use are separate products; therefore, there is no TRUE or EXACT “conversion ratio”. As dermatologists, we must learn how to use each product differently in clinical practice. The injection techniques are similar; however, there are no direct specific or perfect conversion ratios. Regulatory agencies around the world, including the United States, have recognized that these are different products, and there is no interchangeability among botulinum toxin neuromodulators.

Xeomin

Sattler, et al published a non-inferiority trial comparing Xeomin to Botox in the treatment of glabellar frown lines. The independent rater and patient assessment between both products were very similar at weeks four and 12. Because this was a non-inferiority study with two time-points, you can miss the “duration of efficacy” and the “waning effect.” The authors concluded that Xeomin is equally as effective as Botox and both preparations were well tolerated.

Other Considerations

When we look at the FDA studies for the available neuromodulators, they dose the medial corrugator exactly the same as the lateral corrugator and for the convenience of an FDA study. For Botox and Xeomin, it was four units in five injection points and for Dysport it was ten units in five injection points. The reality of our practice is that patients typically have a much more prominent medial corrugator than a lateral corrugator, and when you inject the lateral corrugator with a large dose you risk unwanted spread to the frontalis, which can knock-out the lateral frontalis function of keeping the brow up. So consider lower doses in the lateral corrugator when appropriate, and consider orienting the needle tip more medially to avoid lateral spread to the frontalis.

Combination Delivery

Combining fillers and neuromodulators in the same syringe is not something I would recommend and is considered controversial. It is ok to consider combination therapy, as there is good data on this, but not in the same syringe. In 2013, Drs Cohen and Mariwalla wrote a letter to the editor of Journal of Drugs in Dermatology referencing an article whereby these products were mixed in the same syringe, cautioning practitioners about the potential pitfalls of this sort of approach. Keep in mind that combination same-syringe delivery (e.g. botulinum toxin-A and hyaluronic acid filler ”mixed together”) can be imprecise on many levels, from not uniformly mixed to potential unintended spread of one of the agents. I personally think it would take more time to mix the neuromodulator in the filler syringe, then to simply draw up and inject the Botox on its own—and on its own seems much more precise.

Another important consideration is that of combination neuromodulators and chemical peels on the same day. Swelling can potentially carry a neuromodulator, even a centimeter or two. Use caution on the same day and in same region as procedures that may cause significant swelling with regards to migration, such as non-ablative fractional, ablative fractional, higher concentration chemical peels, and even tightening devices.

Dosing

Remember that dosing, dilution, and reconstitution are different concepts. Dr Cohen reconstitutes his neuromodulators differently by region, using 1cc dilution per 100 units (Botox/Xeomin) in most areas (glabellar, lateral canthus, DAO, and mentalis); however, he uses 5cc for the perioral lines, forehead, platysmal bands, and hyperhidrosis.

When looking specifically at dosing, aesthetic physicians have historically used high-dosages in the forehead, which often caused them to look completely “flat”. “Many patients prefer simply softening the musculature in the forehead without totally knocking it out — achieving a relaxed and natural look. Over the years, Dr Cohen and colleagues have found that they can basically cut the forehead dose in half. This helps in achieving a natural look, softens the musculature and maintains brow shape and positioning–many patients prefer. There are published consensus statements and recommendations on how much product to use and how best to use it for each of the products available. As dermatologists, we also need to consider the anatomic differences between men and women and how we approach the use of neuromodulators in the forehead.

Summary

Remember that all three products have demonstrated positive efficacy and safety profiles. As clinicians, it is important to understand how to use each product, their differences and most importantly, how to individualize treatment and set realistic expectations for our patients. Utilizing the Merz scales or other scales can help with achieving aesthetic treatment goals, by explaining to patients their point on a scale now versus where you are striving to get them to after treatment.

It is critical to understand the changes and differences in the FDA requirements in the studies for neuromodulators. When Botox was approved, studies were designed differently—and improvement was scored differently with follow-up evaluations looking at persistence of some degree of improvement (but not 2-grade improvement necessarily). With Xeomin, a two-grade improvement was required, which was a much higher standard. This is an important concept to keep in mind when looking at responder rates over various studies. With the recent approval of Botox for Crow’s feet, Allergan similarly was held to the 2-grade improvement scale as well.

How to Use Hyaluronidase: Clinical Pearls

February 12, 2014

Joel Cohen, MD

Derek Jones, MD

Dr Joel Cohen and Dr Derek Jones, two of the leading experts in cosmetic dermatology, provide us with some important information on the use of hyaluronidase…

Many clinicians consider hyaluronidase as standard of care, i.e., it is in the office.
Be aware with Voluma because it is a vycross technology not a hyal-cross technology—therefore, its not as easy to dissolve with hyaluronidase, so it may take more concentration.
It takes a fair amount of hyaluronidase to erase nodules with Voluma.
How much hyaluronidase should you use? Some use 150 units per mL; A simple rule of thumb for each 10^th of a cc of Restylane, use about 5 units of Vitrase; (remember that the units across every brand may not be the same); 10 units if you’re trying to dissolve Juvederm; and probably about 15 units for Voluma.
A bottle of Vitrase has 200 units per bottle-so you actually do have to reconstitute with some things so you get more out of it.
Hyalnex is 150 units per bottle.
The shelf-life for the hyaluronidases is very short.
Many people use compounded products, but we’re not sure if they are as effective.
There are a lot of issues with compounding and there will be a lot more regulations coming up.

Tightening Tissue and Zap the Fat

February 1, 2014

Mathew M. Avram, MD, JD

Dr. Avram provides his clinical pearls regarding the use of lasers in tissue tightening….

The Good News, The Bad News, and Overall Conclusions….

Each of the available technologies can achieve some degree of tissue tightening.
They are the best alternative to surgery.
They are getting better.
For the most part, they are safe in skilled hands.
The benefits, if any, require months to be seen.
Too often, no improvement is seen clinically.
It is difficult to predict who will benefit and who will not.
Tissue tightening can non-invasively provide improvement of skin laxity in a safe manner.
Remember that the results are unpredictable.
The technologies do not approach results of a face lift.
It is very important to educate patients as to the limits of these devices prior to treatment.

Laser Treatment of Pigmented Lesions

February 1, 2014

Mitchel P. Goldman, MD

Dr. Goldman provides us with some key takeaway points regarding the laser treatment of pigmented lesions…

Nevus of Ota respond to Q-switched laser—we’ve never seen a report of it becoming melanoma; Picosecond is efficacious as well perhaps with fewer treatments.
There are various approaches to treating lentigines—multiple treatments with lasers combined with bleaching agents, sun screen and sun avoidance In addition, resurfacing and chemical peels may also be effective.
Both congenital nevi and aquired nevi can go away with laser treatment; acquired nevi may be easier to remove (sometimes only 1 treatment is needed); Picosecond also shows benefit with perhaps fever treatments.
Melasma—this is one of the most difficult conditions to treat; it typically has a peak in ages 40-50 and is more around the central face. The most important part of treatment is protection from both sun and other light. Laser and IPL treatment is best when combined with skin bleaching agents. We have found Lytera™ to work best.
Infraorbital Pigmentation-Q-Switch Ruby Laser can help with this; PDL and non-ablative and ablative fractionated and confluent resurfacing is also helpful.
What about lentigo maligna? Q-Switch Alexandrite Laser + zyclara may be an appropriate procedure; however, long-term results are unknown; this is also an alternative approach to patients who do not want to undergo surgery.

BeautiPHIcation-Clinical Pearls

February 1, 2014

B. Kent Remington, MD

Dr Remington, a leading expert in aesthetics, provides us with clinical pearls with regards to the aesthetic consult…

The patient consult is extremely important-spend ample focused time with your patients and find out the “real” reason that the patient wants to look more youthful, not the “stated” reason.
Remember that patients come to physicians for direction.
Pay special attention to details—as dermatologists we are image enhancers and we do all of the creative work—this full face enhancement project is what changes the patients personal self concept and self esteem.
Remember to see in “double vision”—the first vision is to see what the face needs and demonstrate these needs to your patient, so they can visualize it as well ; the second vision is to able to see the end result before you start.
Look for the patient’s best feature and point these out to the patient as they often already know what it is or used, combine this observation with a positive sincere compliment and enhance that feature by performing subtle changes to the face.
Remember that we never really finish a face, maintenance therapy is required.
Educate your patients about the importance of maintenance therapy, most patients intuitively know that they already maintain their house, car, teeth their hair and the face is no different.
Insist on baseline photos of your patients—this allows you to share before and after photos with your patients; therefore, showing them the positive changes.
Have your patients bring an older good resolution photos of themselves front relaxed view usually in their early 20’s—be sure that the photo is in high resolution. The patient needs to understand we are not trying to make them look like this 25 year old photo ,but it is to look at past symmetry, harmony and balance of the face and compare where they are now.
Have a careful planned approach with each patient—each patient has a different recipe for a successful outcome.
When taking baseline photos of your patients, take more than just a frontal view—3/4 and profile views are extremely important.
Patient perception and reality needs to be managed closely.

Beauty and the Signature Feature™

January 30, 2014

Ava Shamban, MD

Dr Shamban is a renowned dermatologist and recognized as a skin care expert. In this presentation, she discusses the concept of beauty and how, as dermatologists, we can improve the aesthetic outcomes for patients by recognizing their Signature Feature™, a concept developed by Dr Shamban.

Dr Shamban reminds us that beauty is an expression of sight, smell, and sound. We want to make beauty memorable and we experience beauty at every level of our brain. Unfortunately, the media is always sending us messages about what we “should” like and this isn’t realistic. It’s important to remember that beauty can really affect one’s self-esteem. Lifestyle issues, such as stress, poor nutrition, diet, alcohol, and sleep can also affect beauty.

We now have a redefinition of aging and that has led to heightened expectations, i.e., what is normal and what is expected with regards to aging. Dr Shamban also reminds us that reaction to beauty is hard-wired, in that “we know it when we see it.”

We have to remember what makes faces and bodies beautiful…

Form

Symmetry
Proportion
Averageness
Defined contour

Surface

Smoothed draping
Texture
Pigment

Another concept that Dr Shamban discusses is that of the positive feedback loop. How we feel affects how we look and it’s a circular concept.

The purpose of aesthetics is to highlight the natural beauty of the individual. Dr Shamban’s Signature Feature™ is comprised of three points:

Feature the particularly beautiful feature of the individual
Persona-the signature feature should be tied to who that person is
Showcase/highlight the signature feature

The goal of cosmetic work is to showcase the signature feature by reducing background noise, which in dermatology is composed of fine lines, wrinkles, textural changes, and brown spots. A blink-test will easily identify the positive feature on a person. As dermatologists, we need to remember that beauty is very important to our patients and we need to use insight and intuition along with the guides and tools that are available in order to help our patients look their best.

Toxins: What’s New, Are There Differences Among Toxins, and What We Have Learned

January 8, 2014

Michael H. Gold, MD

Dr. Gold spends a lot of his time in Asia and, in this presentation, he shares some of the knowledge that he has acquired overseas with regards to toxins. The neuromodulator market is huge and the global medical aesthetic market is expected to post growth of 10.8 percent per year from 2010 to 2015.

Medical Insight, Inc. “Global Aesthetic Market IX Research Report April 2011”, “Facial Injectables Report July 2011” ,“EU Facial Injectables Report July 2011

As mentioned in Dr Cohen’s presentation, it is extremely important to remember that the goal, when using neuromodulators, is a natural and relaxed look for your patients.

Data on Neuromodulators

When looking at the Xeomin clinical trials, dermatologists should remember that responders at maximum frown at day 30 had to have an improvement of two points on a four-point Frown Wrinkle Scale (FWS) compared to baseline by both the investigator as well as the patient. Neither Botox nor Dysport required assessments by both parties. So while the data on the 2-point responders did not look quite as compelling, the numbers for the 1-point responders appeared good.

Mentor, which was purchased by Johnson & Johnson, has completed their clinical trials on a new botulinum toxin, PurTox. Many are hopeful that J&J will submit this data to the FDA in which case we will see this product at some point in the future. Of note, both Xeomin and PurTox are pure toxins. Whether that actually makes a big deal clinically, Dr Gold does not think so; however, it is a wonderful marketing point.

Medy-Tox , which was purchased by Allergan in 2013, is the company that developed a product called Neuronox. It is currently approved in South America and Korea for blepharospasm and tortilcollis. Dr Gold and others feel that Neuronox will not come to the United States market anytime soon. A double-blind, multi-center trial of 173 patients compared Neuronox to Botox in patients with hemifacial spasm. The efficacy evaluation was similar between both groups. A recent clinical study demonstrated the proven efficacy and safety of Neuronox on glabellar frown lines.

Another Korean company, Hugel, makes Botulax. Dr Gold mentions that this company is at many of the meetings to which he goes and they claim to have the Korean version of an FDA approval.

ChinaTox is a product made by Lanzhou Biological Products Institute. It is important to know that many of the other toxins are actually fake ones. An open label study between Botox and ChinaTox looked at 785 patients with focal spasm and dystonia. They found that ChinaTox was less powerful than Botox; therefore, higher doses were required. There were also five cases of skin rashes seen in the ChinaTox group. ChinaTox is; however, cheaper than Botox. Of note, the strain of clostridium botulinum type A was donated from the University of Wisconsin to Dr Yinchun Wang. ChinaTox was approved in China in 1989 and by 2002 the drug has been exported to several foreign countries and is currently in Brazil for both clinical and cosmetic use. ChinaTox has several different names in other countries. This is important to keep in mind as you’re reading various pieces of literature.

Prosigne-Brasil
Redux-Peru
Lantox-Russia
Lanzox-Indonesia

ChinaTox demonstrates similar efficacy as far as other neuromodulators. In Asia, calf hypertrophy is an issue. ChinaTox has shown positive benefits when injected into the calf muscle.

In Russia, there is a toxin, Relatox, with the “Russian FDA-approval.” It was produced at the Federal State Unitary Enterprise Research-Division of Microgen of Russian Ministry of Health. It is available in two dosages, 50µ and 100µ. Relatox is indicated for blepharospasm, cervical dystonia, and facial wrinkle correction and is recommended only for adults. A published article claims that Relatox is comparable to other toxins.

A topical toxin has been developed by Revance using a proprietary platform that enables transcutaneous flux. The first commercial applications will be topical BoNTA in lateral canthal lines and hyperhidrosis. The product is well tolerated and demonstrates up to 89 percent response rate. The median duration of effect is 113 days.

In the US, Myoscience is developing a hand-held medical device for the treatment of facial wrinkles. Essentially, the device uses cold-induced modulation of facial nerves. This has demonstrated promising results in difficult patients and is a new option for toxin-averse patients.

Clinical Pearls

Physicians should only use branded products that are FDA-approved in the US or CE marked in Europe, or products that have received regulatory approvals in your country. There have been instances in the US where non-approved Botox was used and patients ended up paralyzed in the hospital. Physicians are also subject to major sanctions, fines, loss of license, etc. There are many fake products out there….this important to keep in mind as there are serious issues involved with the use of unlicensed botulinum toxins.

Botulinum Toxin 2013

January 8, 2014

Joel L. Cohen, MD

In this presentation, Dr Cohen, a leader in aesthetic dermatology, discusses where we are right now in terms of botulinum toxin. Currently, there are three FDA-approved botulinum toxins type A; these are Botox (Allergan), Dysport (Medicis/Galderma), and Xeomin/NT201 (Merz). Neuromodulators that are on the horizon include PurTox, Neuronox, and China ToxThe three approved botulinum type A products are approved for the use of glabellar lines; however, they are used off-label for other aesthetic purposes.

All three products contain a core neurotoxin protein (150 kD BoNT/A), this is where the mechanism of action lies. Botox and Dysport are wrapped in protein, which is part of the neurotoxin complex Xeomin, however, lacks these accessory proteins.All three products have demonstrated efficacy and have established good safety profiles.

Xeomin

Xeomin has both medical and aesthetic studies. In 2005, Benecke and colleagues published a double-blind non-inferiority trial of 463 patients comparing Xeomin to Botox and concluded that Xeomin is at least as effective and safe in treating cervical dystonia as compared to Botox. Of note, one of the criticisms of a non-inferiority trial is that it utilizes two timepoints, and you don’t know where the subsequent timepoint ends.

In 2006, Roggenkamper and colleagues published a double-blind, phase III trial comparing the efficacy and safety of Xeomin with Botox in patients with blepharospasm. No significant differences were found between the formulations and the non-inferiority of Xeomin compared to Botox was concluded.

It is critical to understand the changes and differences in the FDA requirements in the studies for neuromodulators. When Botox was approved, a one-grade improvement was required. With Xeomin, a two-grade improvement was required. This is an important concept to keep in mind when looking at responder rates over various studies.

Two recently published, identical randomized, double-blind, multi-center, placebo-controlled trials looked at 547 patients. 366 patients received 20µ Xeomin and 181 patients received placebo. Success was defined at a two-grade improvement on a four-point scale. The median onset of effect occurred within seven days after injection and the duration effect was typically up to three months. Single and repeat treatment was well-tolerated. The majority of adverse events were mild or moderate with headache being the most common. There was a 0.2 percent incidence of blepharoptosis following a single treatment.

Sattler, et al published a non-inferiority trial comparing Xeomin to Botox in the treatment of glabellar frown lines. The independent rater and patient assessment among both products were very similar at weeks four and 12. Because this was a non-inferiority study with two timepoints, you can miss the “duration of efficacy” and the “waning effect.” The authors concluded that Xeomin is equally as effective as Botox and both preparations were well tolerated.

A small study of 21 patients by Prager and colleagues compared Xeomin to Botox for the treatment of Crow’s feet. Both products demonstrated high efficacy and good tolerability at a dose ratio of 1:1 with no statistically significant differences between the two. Also of note, the high response rates observed after four months suggest a good effectiveness beyond this observation period.

Conversation Ratios

It is important to remember that the three neuromodulators approved for aesthetic use are separate products; therefore, there is no TRUE or EXACT “conversion ratio”. Dr Cohen emphasizes the importance of learning how to use each product differently in clinical practice. The injection techniques are similar; however, there are no direct specific conversion ratios. Regulatory agencies around the world have recognized that these are different products, and there is no interchangeability among botulinum toxin neuromodulators.

Controversies

It is also important to keep in mind that combination same-syringe delivery (e.g. botulinum toxin-A and hyaluronic acid filler ”mixed together”) can be imprecise on many levels from not uniformly mixed to potential unintended spread of one of the agents.

Another big controversy is that of zinc supplementation on botulinum toxin treatments. A publication in 2012 advocated a proprietary zinc formulation to “extend the durability of botulinum toxin” and “make non-responders, responders.” Dr Cohen found that there were HUGE problems with this study. Zinc deficiency does not seem to be an issue with healthy aesthetic patients, and the article assumes that basically everyone is zinc deficient. Another major issue with this study is that the only physician who injected the product has a financial interest in the product, identified all of the patients for the study, and was an active participant in the study design. In summary, the effect of zinc supplemation with a phytase has yet to be clearly elucidated.

Dosing

When looking specifically at dosing, aesthetic physicians have historically used high-dosages in the forehead, which often caused them to look completely “flat”. “It is important to understand the importance of achieving a relaxed and natural look. Over the years, Dr Cohen and many colleagues colleagues have found that they can basically cut the forehead dose in half. This helps in achieving a natural look, softens the musculature and maintains brow shape and positioning, which is very good for patients. There are published consensus statements and recommendations on how much product to use and how best to use it for each of the products available.

Botulinum Toxin has also shown to improve facial wound healing. Dr Cohen has incorporated its use when performing Mohs closure. This leads to less tension in the scar; therefore less scar spread and a better overall aesthetic look through “chemo-immobilizaton” (Mayo 2006, Flynn 2009)– similar to what has been described peri-procedure with peri-ocular resurfacing (Carruthers) and peri-oral resurfacing (Kadunc).

Dueling

There are many attempts in the literature to try to compare the various neuromodulators. This started from an article published in 2008 in the Journal of Cosmetic and Laser Therapy looking at patient satisfaction with different botulinum toxin type A formulations in the treatment of moderate to severe upper facial rhytids. The patients were switched from Botox to Dysport and, by and large, the patients wanted to go back to Botox. Unfortunately, when studies like this are introduced, Dr Cohen comments that there is a tremendous amount of bias. Often time we see “novelty bias.” Patients return after a second injection and they don’t see the “wow” effect, and there could be “recall bias” as well in trying to remember the effect of the first treatment versus subsequent treatments.

Onset and Duration

The original Dysport trials demonstrated that median time to onset ranged from two to four days. This data; however, was not captured in the original Botox trials. A subsequent JDD trial did actually capture the effect of Botox starting to “kick-in” within the first few days as well.

It is imperative that clinicians be critical of study designs when they are comparing these various products. A meta-analysis looked at the Botox duration effect in the treatment of glabellar lines. Overall, the effect was about four months in 50 percent of patients.

Repeat injections in the same area tend to extend the duration of the product. This has been demonstrated in several studies among all three of the approved neuromodulators.

Summary

Overall, we have good safety and efficacy data among these three products demonstrating that people respond and seem to have better self-esteem (Dayan). Data suggest that, overall, patients look and feel better.