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Fillers and toxins

fillerstoxins2

Fillers and toxins

Our panel of experts discuss filler techniques and complications, as well as toxin resistance and the future of injectables

 

Treating the chin

Mr Rajiv Grover: Dr Brandt, you often use fillers to treat the chin and I think this is a very under-utilised area. In terms of the lower face, the chin has quite an effect on the relationship to the mouth and the neck. Can you expand on how often you tend to inject the chin and any specific techniques you use?

Dr Fredric Brandt: I think the chin is very important to treat past a certain age. Obviously if you’re 25 years old and you want your lips done you don’t need your chin done at the same time. But the chin I always say is a support structure—a foundation for your lips. I tend to use Restylane or Perlane—I use a lot and inject it sub-muscularly. I find if you inject it below the muscle, you’ll get a much smoother result and a better lifting to the area. It depends on the person’s age but I can inject one to two syringes of filler in the chin.

However it doesn’t last as long as on the cheek or certain areas because there is constant muscle movement and muscle tension in that area. Most people need a touch-up in about four or five months.

Dr Michael Kane: Some years ago I wrote a few articles about eyelid injection and tear troughs, so I probably inject more eyelids than anything else, followed by noses—many of the secondary rhinoplasty surgeons that don’t do injections send me these patients. However for people that walk through the front door and want something done, I probably inject the mandibular border, which runs into the chin from the jowl, as often as any area in the face. A patient in their early 40s gets more turnaround with jowl hiding from doing that, than anything else we do.

Mr Rajiv Grover: I think the message we’re getting is that patients come in with a particular problem but a good clinician is one that can look at their face, analyse it and tell them what they need rather than what they’re asking for. Dr Flynn, your thoughts on the chin?

Dr Timothy Flynn: I agree, it is an under-treated area but my least favourite line in the face is the marionette line. In order to treat the marionette line you have to put structure in the lower area. There can be a lot of sinking occurring there, so once we’ve treated that and lifted the marionette up—as it’s such an obvious sign of ageing—then I may augment an area in addition to the chin, just to restore. We’re all doing more mid-face going down to the lower face and augmenting as we go along.

Dr Nick Lowe: Chins can be improved considerably, in some instances just by using one of the deep volume fillers—my favourite is Voluma. I’ll inject it in the sub-muscular area and I may even do it over more than one session. I bring the chin forward and it’s very useful to treat regressive chins and also helps to define the jaw line.

Don’t be afraid to bring the patient back after a month or so and do a little bit more. Another way to achieve longer lasting results if you are treating a very mobile mentalis muscle with the puckering peau d’orange appearance, choose your time to put some botulinum toxin in the central muscle to diminish puckering and movement and help the filler last longer.

Mr Rajiv Grover: That’s the message of the Carruthers paper about treating the glabellar with a combination of toxins and fillers—if you reduce the movement, the lifespan of the filler is a little longer. The other thing that I found when treating the chin is definitely use a cannula because it is quite a vascular area.

I treated a lady with some Restylane SubQ to the chin whilst performing a facelift—at that time I was using the needle—and I got more bruising from this than from the entire face and neck lift. You can get quite dramatic bruising in some individuals so definitely use the cannula.

What are the thoughts of the panel on needle versus cannula, and do you have any preferences in particular areas?

Dr Fredric Brandt: I think it depends on the physician and what they’re more comfortable with—whatever works better for you. I happen to use cannulas for the cheek area, for filling facial compartments. I don’t use them for the temple because it’s too hard to get through that fascia  for me to get to the periosteum.

I don’t use it on the chin because it’s too uncomfortable to get under the muscles for the patient so I tend to use needles. I do agree chins bruise more, but I find it’s hard to be comfortable getting deep in the muscle without the patient feeling a lot of moving those muscles around and it is a little traumatic for them.

Mr Rajiv Grover: I do inject with local anaesthetic which I suppose defeats the point of not using a cannula because there’s a needle to put it in, but I do infiltrate with a little bit of local in the actual chin because it’s quite fibrous. I agree, it would be difficult to push through but as I anaesthetise, it’s a little easier. Michael?

Dr Michael Kane: I experimented with cannulas a couple of years ago and really gave it a go for a while but I’m mostly a needle person now, although I’ll occasionally use cannulas. The only area I would almost always use a cannula is the dorsum of the hand. You have pros and cons everywhere. I tend to put my filler superficially in the dermis and I don’t think you can do that with a cannula.

When you’re using a cannula you’re putting your filler deeper and I think you have a little less volume control. I like to use really tiny needles and shearing down the particle size, so I like the control with the needle. Since you’re deeper with cannulas, I think you need more product per gain, or something that you can see in the skin, which is a disadvantage.

Patients bruise a little less when using a cannula but I think you beat up that port hole a little bit more than you do when injecting with needles. So they each have their pros and cons.

Mr Rajiv Grover: I’m also reminded that your referral base is often people who may have had previous surgery, revision cases, eyelids, noses—they’ll be very difficult with a cannula so the needle will break through the scar tissue. That’s probably also your practice, Tim?

Dr Timothy Flynn: I’m very similar to Michael. In the back of the hands, which I traditionally treat with Radiesse, I’d use a 22G, two to three inch cannula. Cannulas are interesting because the other area where I use them is in fat transfers. When harvesting fat I still use the 18G Coleman fat transfer cannula—I would just re-sterilise. That’s a big cannula but for those of us who have experience in liposuction it’s used in the same way.

You have to have a certain amount of controlled force as you move through the tissue and deposit. So I would say for me, I use cannulas for fat transfers and back of the hands only, otherwise needles.

Dr Nick Lowe: I use more cannulas than the others. I did a clinical audit for the Care Quality Commission on the use of fillers and, from 150 responses, 60% were injected with cannulas compared to 40% with needles. I use needles if I’m lifting and I want to put filler straight into the periosteum, on the malar eminence or onto the zygomatic arch to lift with one of the deep volume fillers.

If I want to fill, I will use one of the modern cannulas. If I want to define the lip border or inject the jawline I will use a cannula. The other thing our audit showed us is that there was a 20%—25% incidence of bruising with needles and about half that with cannulas.

 

Volume in the cheeks

Mr Rajiv Grover: What would be the average volume you would inject into your cheek patients for example, both ideally and what you actually do in practice?

Dr Fredric Brandt: It’s so variable depending on what the patient is looking for and what the aesthetic is.

Many people are afraid to have huge cheekbones now because they see a lot of cheeks that are over-inflated, so it depends on the patient. I don’t think you need that much volume, and it depends if they’re a virgin patient. Maybe 1cc per cheek, perhaps a little bit more if you want to be dramatic.

It also depends on their age. If somebody comes in in their 40s, you just need a small amount. Somebody in their 60s or 70s is going to need four times that amount. You can use anywhere from 1cc for both cheeks to 4–5cc on both cheeks, really depending on the age and what you’re trying to accomplish.

Mr Rajiv Grover: That is very enlightening to me because I was expecting for Upper East Side New York high volumes and yet you started off with very low volumes which for us in the UK is reassuring. Michael?

Dr Michael Kane: I think it depends. There are two patient cohorts—the person you see for the first time that wants to get maxed out and filled up and the person who comes back for maintenance.

That first time patient may get seven, eight or ten syringes over the whole face, but if they come back in four or five months they’re getting one syringe or two syringes spread over eight areas of the face. So if you were to take my last 100 charts, because it is so variable, and look for that median dose, it would probably be 0.3cc or 0.4cc per cheek—very small volumes.

Dr Timothy Flynn: I’m the opposite of Michael simply because of the patients that come to see me in my rural type university environment where I live. I would usually like to put more volume in the cheek than they’ll let me, largely due to cost and the fear of looking different. I may end up getting to where Michael is by repeat injections about every two to three months.

On initial injection I would tend to use Radiesse which I would dilute 1:1, and put about 1cc in each cheek in the deeper fat pads. Then when they come back to see me I may add an additional 2–3cc later on. It’s totally age dependent though. When a patient is young, we use a little. When a patient is 55–65, we have to do a lot more volume restoration.

Dr Nick Lowe: I agree with Tim here entirely. It depends on the age and the degree of volume loss. After weight loss, post pregnancy or post partum I tend to use a little bit more.

But my average would be no more than 2cc per side to start with, and most of my patients don’t want to suddenly look different. They want a gradual improvement so I’ll ask patients to come back after a month or so. If you then layer on top and re-finesse it you not only get more bang for your buck but you also get it to last a bit longer.

Mr Rajiv Grover: I find the cheeks really last a long time once you do them a few times.

Dr Timothy Flynn: What’s also interesting is that cosmetic patients will find the practitioner that suits their needs. Somebody who’s looking for a more dramatic result may find an injector who does a higher volume and somebody who is concerned about an obvious outcome may find somebody who does just a little bit and over time, will get enough treatment to achieve good correction.

Mr Rajiv Grover: Are there any problems with migration in the cheek?

Dr Timothy Flynn: I don’t think there’s a lot of migration but I use relatively small volumes in that space so maybe I’m injecting small, discreet packets.

Dr Michael Kane: I think there’s less migration if you’re injecting deep. You get slightly more migration when you’re injecting more superficially, but if you’re injecting on the periosteum and building a tower like Gerhard Sattler described, then you’re not going to get much migration.

 

Resistance to toxins

Mr Rajiv Grover: The biggest barrier to treatment in this country is trust, and you build trust by doing things gradually. The next area that I want to discuss is resistance to toxins. According to a feature in The Sunday Times Style Magazine there is a big problem because people develop antibodies and they become resistant.

I don’t see so much of this and one of the arguments related to whether or not the different botulinum toxins that are available now have different levels of foreign protein in addition to the botulinum. So do they have different effects on patients becoming resistant?

Dr Nick Lowe: Yes, I think I was one of the culprits quoted in that article. In fact, we were able to prove quite clearly that several patients had acquired resistance to all three Type A toxins that we have in this country. It does occur but it’s rare in my extensive experience. I’ve had five that I can say have definitely developed an acquired resistance to Type A.

Mr Rajiv Grover: And you wouldn’t say that any of the Type A toxins are any different to each other?

Dr Nick Lowe: I tried all three Type A toxins in these patients and none of them responded. Is it going to be less with the ones that have less protein, like Incobotulinumtoxin known as Xeomin? I don’t know. I don’t think anybody knows because the problem is that you can get resistance in the absence of antibodies against botulinum toxin and you can get antibodies against botulinum toxin and you can still get responders. I don’t think it’s been worked out and I think it’s a different pharmacological mechanism than antibody formation.

Dr Timothy Flynn: What we can say for sure is that at cosmetic doses it’s a relatively infrequent occurrence.

Dr Nick Lowe: It is very infrequent.

Dr Timothy Flynn: Nick, were these patients complete non-responders or did you pick up on a partial response or decreased response to what they were having to the injections?

Dr Nick Lowe: They were patients who I’d been following for some time. They were previous responders and they became total non-responders.

Dr Timothy Flynn: It is a very interesting phenomenon. Certainly this idea of resistance is more seen in therapeutic doses, so if you have cerebral palsy or any of the other neuromuscular disorders where patients are using hundreds of units, then you have problems with resistance.

Dr Michael Kane: I’ve been injecting toxins for 22 years and have probably injected about 30,000 people and I’ve had two non-responders. It doesn’t matter if they’re demonstrable antibody positive or negative—we’re talking about non-response and we’re looking at the wrong cohorts. That is not going to come out of our world, it’s going to come out of the physical medicine world where in long term studies over 2% of people become non-responders.

The hapten effect means that a protein load can stimulate your immune system and up-regulate your cells to start making antibodies. The idea that the other toxins with more proteins are priming the pump and creating more antibodies remains to be seen and we’ll probably know within a few years. If there are matched trials in the physical medicine world with giant doses that are given much closer together, we’ll start to see something.

In response to your question, I think it’s both things. I think it’s dose and timing or interval but probably interval is more important. There are a few studies in murine rats where they’re given toxin doses, and I wrote a commentary on one. It seems that depending how accurately you can measure for antibodies, after one dose you can measure some response. It’s just not a clinically significant response. They don’t become non-responders. And it seemed in several studies, including this one, that this interval was more important than time.

Dr Fredric Brandt: I agree with Michael—I think it has more to do with interval than amount. The problem I face in my practice is that people come in and want touch-ups and if you don’t give it to them, they’re going to go somewhere else. It becomes a problem. Especially in New York, I find that if patients see one muscle moving they want to come back instantly so it’s hard to keep them on a four-month schedule.

Dr Michael Kane: First of all let’s define the touch-up. If someone comes back and their DAOs are a little off and their mouth is crooked, that’s something you have to fix. The question is if they want a little more—you’re going to do it typically to keep them happy but I will read them the riot act and explain that long term, it is not a good idea as it may increase the chance of becoming resistant. If a patient returns and asks for another touch-up, I’ll give them the talk again and gradually they tend to do it less. They listen to you.

The two patients I had who were non-responders were not garden variety patients. One was the wife of a plastic surgeon and so had a lot of Botox with short intervals and became a true non-responder.  The other was a patient who was getting a lot of toxin from several different doctors back in the mid-90s. Back then, before they changed the batch in 1997, there was a much higher protein load in botulinum toxins and it wasn’t just accessory proteins, it was inactive neurotoxin as well. This is the real danger because it primes the immune system. Since they cleaned that up, the amount of these incidents seems to have gone down.

Dr Fredric Brandt: I find that in those patients who are not responding to Botox, I’ll switch them to Dysport or Xeomin and they do very well. You can try switching them around and in certain cases you’ll get longer duration of action.

Dr Nick Lowe: I think that’s partly true. I do the same to keep some of my patients happy. I have a group of patients that definitely have longer duration with one of the toxins compared to the other. I think Dysport is better for crow’s feet, possibly because you’re getting more migration into the orbicularis oculi. But I think the incidence of true resistance is so rare in the dosages we are using for aesthetic use that it’s probably a rarity that’s interesting to us partial academics, but it’s not a major clinical problem.

 

The future of fillers

Mr Rajiv Grover: What might be the future in years to come—what will be the next paradigm shift for fillers?

There’s talk that they will include skin modulators to try and stimulate, in the way that fat grafting does with stem cells, fibroblast proliferation and rejuvenate the skin as well.

Dr Fredric Brandt: I think it depends on where you’re injecting the filler. With products to improve skin texture, you’re probably going to see fillers that are injected with a gun or very superficially into the dermis. Maybe in the future we’ll even be able to inject products that will affect bone and the deeper level, or be able to include an antimicrobial substance that will prevent formation of bacterial growth in the substance. We don’t need a filler that lasts five years in the face—I think the fillers we currently have available already last quite a long time if they’re done correctly.

Dr Michael Kane: I think two big things are going to happen. One is already here and is currently undergoing trials and one is a little further in the future. I agree that fillers last as long as they need to and I don’t need my fillers to last any longer because you can get great longevity with what we have. But patients always want that—if you were to give a patient a questionnaire, that would be the number one request.

So I think what we will see is peptides being used more. We don’t have much mesotherapy going on in the States and some peptides clearly have efficacy. Some peptides are thought to have anti-natural hyaluronidase qualities, so by incorporating those peptides into hyaluronic acid, the natural enzyme is prevented from breaking it down so the filler lasts longer. That’s one interesting thing.

The second advance involves solid state HA threads, which use regular HA cross linked with BDDE and polymerised to make it a smooth thread—it comes on a long Keith needle. It’s a different way of delivering HA that’s very volume controlled. I have patients who I treat for 45 minutes to an hour, working on those horizontal wrinkles in their forehead because they have tremendous brow ptosis and are constantly working their frontalis—you don’t want to drop them further. I can do that but it’s a pain in the neck. It’s a very unforgiving area with the light coming down, and it’s all about volume control.

If you use these threads, you can put in a perfectly dosed volume right through each of those lines. There is a study currently going on in Canada with these threads—I don’t know how soon they will come to market but while they won’t replace gels and needles, they could be a nice addition for those difficult to treat areas.

Dr Timothy Flynn: If we could get stem cells to focally improve and proliferate certain areas, such as an agent that caused fat stem cells to turn into a mature adipose site, it would be great to be able to put that into an atrophic fat pad. People are playing around with fat; you can grow bone out of fat, which is amazing. If that technology goes forward, we could control where the proliferation occurs—that would be very attractive.

The problem is we can get problems with cellular proliferations so we have to look at the long-term side effects. It’s one thing to transfer an adipose site, but it’s another to try and take something and get it to change and mature and grow. You’ve got to make sure there’s no uncontrolled growth which is a result of causing the stimulation to those cells.

Dr Nick Lowe: It’s fascinating to conceive of a hyaluronic acid injectable being an excellent vehicle for a whole variety of different active peptides and active growth factors. There are some fascinating peptides that I’ve come across in putting my skincare product hat on that are really being refined very nicely, including neocollagenesis and even peptides that can regulate inflammation and pigmentation.

I’m sure there can be biologically active non-peptides that could be incorporated into a hyaluronic acid as injectables, one that could then stimulate more fibroblast activity. The problem is, as Tim has said, do you really want to stimulate too much fibroblast activity? Every time you add an additional complication and additional complexity, you add the potential for extra complications and side effects.

 

Complications

Mr Rajiv Grover: The last topic we’re going to discuss is complications. One of the things that concerns us about injecting larger volumes into the cheek—because you’re effectively putting in an implant rather than a filler—are the inflammation or biofilm-type effects. What would be your finding of these incidents and what would you do practically to try and reduce the effects of biofilms or these types of complications?

Dr Fredric Brandt: We always say biofilms—but is it truly a biofilm or is it more of a streptococcal antigen in the product that the patients are reacting to? Is it something else that has stimulated the patient’s immune system? When somebody gets a dental abscess, you can get a nodule but is it the bacteria going into that area or is it just a heightened immune response? I think that there are certain cases where we’ve seen certain batches of material react more than the other so we don’t know if it’s a manufacturing defect.

To treat a nodule resulting from hyaluronic acid, the best thing is to dissolve it right away with hyaluronidase. You can give the patient Biaxin, Doxycycline or Minocin but we’re not sure if it’s the antimicrobial or the anti-inflammatory effect that’s working to suppress the immune response.

We know it’s an immune response but we don’t have a lot of histological data to prove that it’s truly a biofilm. Is it just a heightened immune reaction to some of the protein that we know that these materials come from—strep antigens are not always washed out completely and there are different degrees of purification.

We need to know what we’re actually treating. However I think if you have a reaction to hyaluronic acid, just get rid of it with hyaluronidase.

I’ve seen patients where I’ve injected a syringe and 90% of the areas won’t react and one area will react on the face and it’s not related to an infection. Usually when it’s an infectious process it lights the area up. But I’ve seen cases where just one area reacts and I can’t figure it out. Was there more protein in that area, was the product not purified? It’s a gel so not everything is distributed equally through it. So in the manufacturing process, they may have more foreign body in one portion of gel than the other.

The patient had no obvious infection process. I’ve had a couple of patients that have dental abcess, their cheeks blew up and the abscess was cleared in a day. But then there are other patients who react and they have no obvious sign of infection. We didn’t do an ID work-up and we didn’t draw blood cultures but they have no dental pain, no sinus issues, no obvious other infectious signs in their body and it’s one area—not the whole face—that’s blown up. It’s one area from the same syringe. I have other colleagues and we talk about this and we can’t figure out why that happens but it does happen and I think if you use enough of any filler you’re going to see it.

Dr Michael Kane: I agree with Fred. We don’t know what’s going on. I’m not sure if it’s a little antigen in there or if you’re really getting a biofilm. There were reports about the early batches of Restylane in the 90s where people were getting “little red bumps” or inflammatory episodes. But since they cleaned up the proteins, it has became much less common.

I’ve seen one person who called me up and said they thought they had the little red bumps. She came in and I think she had a little zit on her face which was a little inflamed, so I put her on Doxycycline because that’s what we’re supposed to do. Now, it got better. I don’t know if that’s because of its antimicrobial effect or the anti-inflammatory effect. However, I do think that if I had given her nothing, it would have gone away.

Dr Timothy Flynn: Do we really see this much of a problem in real practice? How many people are really calling up our office and saying I have these terrible angry red bumps? We don’t see it really all that much. I think we need careful cleansing of the skin, using a sterile technique when you implant it and injecting small amounts in a distribution rather than one large pool. I just don’t think it’s as much of a concern as we all talk about.

It is a mystery in a sense because when it does occur, it could be injected in a variety of areas but there’s that one area which has become inflamed. What we really don’t have is people taking a little blade, nicking that and then culturing it in order to grow out a micro-organism.

Dr Fredric Brandt: I had a colleague in New York who had somebody do that—she was at university and they couldn’t grow anything. But how do you know if you’re getting enough material to culture? It’s not like you’re getting pus out that you can really culture. So I agree it’s a great idea but this was in a university setting so they had a whole department there to handle it and nothing grew.

Dr Timothy Flynn: I think that’s quite interesting because in defining an infectious process, you’d like to prove what the infectious process was caused by and we have a lot of trouble proving that.

Dr Nick Lowe: I don’t think these are infectious processes. My own suspicion is that it’s a fibrotic reaction around some fillers. I had a patient that I’m currently treating who was very negligent, or I was negligent about pushing her on a clear history about what fillers she’d had before. She only said that she’d had several Restylane and Juvéderm before but as it turned out, I injected her with a little bit of Voluma, just 0.5cc each side, and two weeks later her left cheek ballooned.

On closer questioning, she’d had Bio Alcamid ten years ago, and I am quite convinced that during the course of my injection, there was a fibrotic capsule around the Bio Alcamid—I disturbed that and it caused an intense inflammatory response. I cultured it, and while the cultures are pending, they are until now totally negative.

I’ve asked for different cultures and tried to do a biopsy, which she declined and I don’t blame her. So she’s on low dose antibiotics, she’s on hyalase and intermittent Triamcinolone injections as needed and we’re getting an improvement.

Author: bodylanguage

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