When Mirela first got lip filler in June 2021, she expected a confidence boost. But noticing the hyaluronic acid (HA) filler migrating above her lip, she started to worry. “It was very painful, especially in my top lip,” the 30-year-old from Sweden told VICE.
After researching online, she found sites claiming she could have the HA filler “dissolved” with an enzyme, hyaluronidase. The U.S. Food and Drug Administration, Therapeutic Goods Administration Australia and other global health regulators don’t approve of this practice. Yet practitioners said the enzyme is widely used to degrade HA filler and treat complications like Mirela’s.
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“Hyaluronidase was initially used to place a local anaesthetic in people during surgery so it spreads better,” Dr Ben Talei, a plastic surgeon in Beverly Hills, told VICE. “We started using [hyaluronidase to dissolve fillers] pretty much the same time that hyaluronic acid fillers were invented.”
“I asked different clinics about side effects [of hyaluronidase],” said Mirela. “They said there is just a little bit of bruising.”
In August, Mirela had a hyaluronidase patch test on skin, to test whether she was allergic, before having 150 units injected into her top lip. The next day, Mirela says she felt burning in her face, neck, and even on her arm where she had initially had the patch test. Terrified, she sought help from her injector, who told her to go to a doctor. When she went to her general practitioner, she was told to go back to her injector. Eventually, she went to the emergency room.
But as soon as she explained her situation, she was sent home. Mirela said she was in agony for two weeks. “I saw my face changing all the time,” she said. “I was very weak. I couldn’t sleep or eat.”
In the months after, Mirela noticed her eyes sinking into her face and her skin losing significant volume. She still experiences occasional burning in her face and arms. “The fat underneath my feet feels very soft, so I’m walking worse.”
Mirela is not alone. Over 2,000 people—many with similar experiences—are part of a Facebook group discussing the adverse side effects following Hyaluronidase treatment to “dissolve” their fillers, as well as the fallout of HA fillers themselves.
Many of them report side effects, including their face “dissolving”, burning skin sensations, loss of skin volume and elasticity, neuralgia, dry eye syndrome, headaches, pressure in the face, constant fatigue and more. Some report feeling stuck in medical limbo—experiencing rare side effects possibly linked to a treatment that hasn’t been adequately studied.
Because of a lack of clinical trials, the stories of those who have experienced adverse side effects to the treatment are not conclusive. But they do highlight a glaring lack of research into this increasingly popular, off-label, and unregulated procedure.
The Hyaluronic acid filler boom
Hyaluronic acid fillers are one of the most popular non-surgical cosmetic procedures—second only to botox. The International Society of Aesthetic Plastic Surgery’s latest data shows that over 4 million procedures were done in 2020, a 20.2 percent increase from 2016.
Why are they so popular? Most people recover quickly—bee-stung lips and corrected wrinkle lines are ready within days. Also, because we have hyaluronic acid in our bodies, HA fillers are perceived as safe and natural. There is a widely-held belief that your body can reabsorb them over time, even within months. “My perception was that HA fillers were preventative, anti-ageing and good for your skin,” Ash from Orange County, California, told VICE. The 27-year-old said she also felt influenced by social media—where the caricaturistic pillow face look and aesthetic ads are omnipresent.
Yet practitioners recognised that as the popularity of fillers has increased, so have complications—including persistent filler residue. “We still see filler in large amounts after 15, even 20 years,” Daniel Ezra, an oculoplastic surgeon in London, told VICE.
This is partly because the Hyaluronic acid filler we put into our faces is not the same as the hyaluronic acid we naturally have in our faces. “It’s not a natural material. It’s hyaluronic acid that we make synthetically and put in the face,” said Dr Talei. For example, synthetic Hyaluronic acid filler is highly cross-linked, meaning the molecules have been linked with other compounds to make the filler last longer. “Different fillers have gotten different degrees of crosslinking and different concentrations,” Ezra said.
“Fillers can [also] cause different types of swelling and changes in the face long term,” Dr Talei said. Other complications include granulomas, migration, swelling, rash, the Tyndall effect and an overfilled face.
As filler complications increase, so does the demand to remove them. Patients can wait for it to disappear, have it surgically removed or seek hyaluronidase.
Dr Talei said that “dissolving” has become more popular in the last two years. “That may have something to do with people publicly saying, ‘I overdid the filler.’” Talei was referring to Kylie Jenner, who had her lip fillers dissolved in 2018. Courtney Cox, Huda Kattan, Molly-Mae Hague and Daisy Marquez have also dissolved their fillers, fuelling the trend.
What is Hyaluronidase?
For 60 years, hyaluronidase has been used to improve the diffusion of local anaesthetics. It breaks apart the glycosidic bonds in HA. In aesthetics, its regulated use is to treat vascular occlusion: a rare yet serious complication that can happen during filler-injection and cause necrosis, stroke and blindness.
But experts confirmed that the off-label use of hyaluronidase to dissolve HA filler is not illegal or new. The Aesthetic Society first published data on the treatment in 2020, when over 14,000 filler reversals were performed in the US. Last year, that figure jumped by 57 percent—over 23,000 filler reversals were recorded in the U.S.
Surgeons said that the procedure can be effective. “When you put hyaluronidase into HA it dissolves fairly immediately. I can put it in, massage it out and see a difference within minutes,” Dr Sue Ellen Cox, a board-certified dermatologic surgeon in North Carolina, told VICE.
Yet few human trials on this procedure have been done. Those that have are based on limited participant pools. Studies usually focus on how much hyaluronidase to use: one says nine units, another says there’s no difference between using 20 or 40 units. One found different fillers respond differently to Hylenex hyaluronidase. Another concluded that different HA fillers have varying levels of sensitivity to different hyaluronidases.
“You don’t go to a class on ‘how do I use hyaluronidase?’” Dr Matarasso, former president of The American Society of Plastic Surgeons, told VICE.
As the treatment is off-label, there is no consistent, recommended injection dosage. Recommendations in the literature range from less than 5-75 units per injection site. This lack of consensus is reflected in patients’ varying experiences. Olivia*, 31 from Australia, received about 60 units in each of her tear troughs. Svetlana, 37 from Russia, said she was injected with 9,000 units over 16 sessions.
“The practitioner should potentially be using the smallest volume [of hyaluronidase] that they can,” Dr Matarasso said.
What do we know about Hyaluronidase?
We know hyaluronidase can cause delayed allergic reactions that patch tests don’t detect, and that different fillers respond differently to varying doses of hyaluronidases. Highly-concentrated and crosslinked fillers are also less responsive to hyaluronidase—requiring more injections. This could explain why some patients described having residual filler years after hyaluronidase injections.
Practitioners acknowledged this treatment can cause damage. “There are patients who, after being fully dissolved, are in a worse place than they were initially. It’s a small proportion but it’s not insignificant,” Ezra said.
The natural HA that we have in our bodies can hold up to 1,000 times its weight in water. “Hyaluronidase breaks down your natural HA as well as the HA that was injected,” Dr Talei said.
He explained that when your natural HA is depleted, your body’s ability to retain fluid diminishes. While most patients recover in two to three weeks, he also said that’s not the rule. “Some people can take one to three years.”
“You can put HA filler [in your cheek] and it can move. When you try and melt it with the enzyme, you’re chasing something and it can also melt some of your normal tissue,” Dr Matarasso said. He also pointed to the challenge of practitioners treating new patients with hyaluronidase, without necessarily knowing which filler was previously injected or where. “Hyaluronidase may not help [that patient] and could even harm.”
Dr Derek Jones, a board-certified dermatologist in Beverly Hills, said injecting too much unevenly into an area with lots of filler can cause skin concavities. “That is more related to erasing the filler than to harming the skin,” he told VICE. He said he has injected thousands of patients with hyaluronidase over 16 years, and never encountered the problems these patients experienced.
Multiple patients said they were not warned that hyaluronidase could break down their natural hyaluronic acid.
Emerging data on Hyaluronidase
Data has not caught up with widespread medical practice. Ezra hopes to change that. He plans to publish a study of over 100 patients experiencing adverse side effects: skin discoloration, skin contour changes, change in skin quality and hollowness. He found that this reaction is related to how much filler was in the body, for how long, its dilution, and its distribution. “It is very likely to be the filler that was there that was damaging the native connective tissue. Only when it’s removed do you see the effects.”
His study does not examine myriad other side effects patients reported. “Hyaluronidase affects connective tissue. But I don’t think it’s a significant effect to explain the problems people are experiencing,” he said. “It’s likely to be a combination of… damage from the filler and lesser effect from the hyaluronidase.” Dr Talei held a similar opinion: “Having filler in the face could be a nidus.”
Can “dissolving” with Hyaluronidase cause adverse side effects?
There is no clinical data suggesting a causality between using hyaluronidase to “dissolve” and these adverse side effects—and some practitioners reinforced this. “Remote changes in the body from a hyaluronidase treatment in the face is exceedingly unlikely,” said Dr Talei.
But by the same token, no data suggests a lack of causality. “When we talk about our side effects [we are told] it’s in our heads. How did we make it up if there are no clinical studies?” Anastasia*, 24 from Russia, told VICE.
“With rare complications, you can never really conclude on them unless you’ve got a large enough data set. You need tens of thousands of patients to do this,” Ezra said.
It’s also unclear whether these reactions are linked to HA filler. One paper noted that delayed reactions to HA filler have been increasingly reported in the last five years. If filler does indeed play a role, how can we know the true extent?
Experts and the U.S. Food & Drug Administration emphasised HA fillers and their removal come with risks. “Although the FDA recognizes that procedures are being performed to remove fillers, it is critical that patients understand that fillers can be difficult to remove, or may not be successfully removed at all,” an FDA spokesperson said.
“The FDA has not approved any products for use to remove dermal fillers. Doctors may decide to use approved products for unapproved uses within the practice of medicine.”
A spokesperson for Australia’s Therapeutic Goods Administration (TGA) said it has received seven reports of adverse events involving hyaluronidase since 2015, related to anaphylaxis and allergic type reactions.
Dissolving dermal filler was not in the TGA’s list of approved uses for hyaluronidase (referred to in Australia by its brand name, Hyalase). “It remains open for doctors to prescribe medicines ‘off-label’ based on their own clinical judgement. Off-label use is not illegal or banned by the TGA but is subject to the clinical discretion of the doctor with consideration of the potential risks and benefits in the setting of informed consent,” a TGA spokesperson said.
A spokesperson for Halozyme, manufacturer of Hylenex hyaluronidase, said some of these adverse side effects occur with specific dermal fillers when used alone. “As the dissolution of HA fillers is not an FDA approved indication, we do not promote the use of Hylenex for dermal filler reversal.”
A spokesperson for Merz, manufacturer of Belotero filler, said they couldn’t provide specific guidance on the use of hyaluronidase to dissolve HA filler, and that off-label use is at the discretion of the health care professional.
Hyaluronidase manufacturers Bausch + Lomb, Petrovax and Sanofi Pharmaceuticals did not respond to requests for comment. Riemser, the manufacturer of Hyalase “Dessau”, declined a request for comment.
HA filler manufacturers Allergan, Galderma and Fox Group International did not respond to requests for comment.
Lack of research doesn’t just mean more potential sufferers. It also means a lack of diagnosis, treatment, redress and closure for those already suffering. Hazel*, 52, is a UK-based social worker who supports over 100 patients through Facebook and WhatsApp groups online. She told VICE that many reported being turned away by injectors and doctors.
“I can give psychological support to people, but they need medical attention.”
* name has been changed for privacy.
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