Dermal Fillers and Vaccine Reactions: How to Prepare Patients for the Rare Possibility

No one expected dermal fillers to be an obstacle to widespread COVID-19 vaccination. But when reports emerged that three patients had experienced facial swelling after receiving the Moderna vaccine—and that a history of hyaluronic acid dermal filler injection was the common denominator linking these reactions—some people began expressing hesitancy to receive the vaccine.

Lara Devgan, MD, MPH, a board-certified plastic surgeon in New York City, told Allure magazine that she had “patients saying they’re too scared to get the vaccine because they like their fillers.” Unsure if her patients were outliers or representative of a larger trend, Dr. Devgan polled her 410,000 Instagram followers and was shocked to learn that 27% of those who responded said they’d also refuse the vaccine due to concerns regarding filler/vaccine reactions (Allure. January 20, 2021).

When the first filler/COVID-19 vaccine reaction reports emerged in December 2020, reported through Moderna’s FDA Briefing Document, “there was limited information, so we didn’t have much data to go on to advise patients,” said Theda Kontis, MD, an associate professor in the departments of otolaryngology–head and neck surgery and plastic and reconstructive surgery at The Johns Hopkins Hospital in Baltimore. “Physicians were making up their own rules about when to inject or not inject fillers around the timing of patients’ vaccinations.”

Since then, additional data have revealed that filler/vaccine reactions are rare, self-limiting, and little threat to overall health. However, the spate of attention generated by news of vaccine reactions in patients who had previously received dermal filler injections highlighted an important fact: Given that more than 2.6 million visits for filler injections occur annually in the United States (Facial Plast Surg Aesthet Med. 2021;23:75-76), and that today’s fillers can persist in the body for eight years or more, otolaryngologists and other physicians play a crucial role in educating patients and managing vaccine reactions.

“As physicians, our primary responsibility is to consider the bigger picture in the health and safety of our individual patients and also society at large,” said Arianne Shadi Kourosh, MD, MPH, assistant professor of dermatology at Harvard Medical School in Boston.

Reactions to COVID-19 Vaccines Are Rare

The worldwide incidence of delayed inflammatory reaction (DIR) occurring because of any triggering event—not solely COVID-19 vaccine injection, or vaccine injection more broadly—is “thought to be 0.8%,” according to a 2021 JAAD Case Reports article (JAAD Case Rep. 2021;10:63-68).

The fact that these reports are still relatively few, now that public vaccinaation has been online for months, suggests that it’s a pretty rare occurrence.  —Arianne Shadi Kourosh, MD, MPH

The three reactions reported among the approximately 15,000 patients who participated in the phase 3 trial of the Moderna vaccine and who received at least one dose of the vaccine included facial swelling in a 51-year-old female that appeared two days postvaccination (and two weeks after dermal filler placement), facial swelling one day after vaccination in a 46-year-old female who had dermal filler placed six months prior, and lip angioedema two days after vaccination in a 29-year-old female who had filler placed an unknown length of time previously (ModernaTX. Vaccines and Related Biological Products Advisory Committee Meeting December 17, 2020; American Society for Dermatologic Surgery. Guidance Regarding SARS-CoV-2 mRNA Vaccine Side Effects in Dermal Filler Patients. December 28, 2020). Two of the patients in the trial’s placebo group also reported facial swelling (Int J Womens Dermatol. 2021;7:209-212).

According to the United Kingdom’s Drug Safety Research Unit and JAAD Case Reports, facial swelling has also been reported in patients with a history of dermal filler injections who received the Pfizer-BioNTech COVID-19 vaccine (JAAD Case Rep. 2021;10:63-68). No incidents of facial swelling or possible filler/vaccine reactions following receipt of the Johnson & Johnson COVID-19 vaccine have been reported yet in the literature.

It’s impossible to determine the true prevalence of COVID-19 vaccine/filler reactions without knowing how many patients have previously undergone filler injections. The three reactions reported in the Moderna trial were likely a tiny minority. “Given national statistics on the order of millions of filler injections done in the U.S. annually, there were probably more than three people in that clinical trial who had filler in their face,” said Dr. Kourosh. “The fact that these reports are still relatively few, now that public vaccination has been online for months, suggests that it’s a pretty rare occurrence.”

L. Mike Nayak, MD, a board-certified facial plastic surgeon in Missouri, said his large practice hasn’t noticed a significant uptick in DIRs in recent months, despite increasing COVID-19 vaccination rates.

“I’ve been seeing more questions and attention to it than actual responses,” Dr. Nayak said. “Personally, I can’t think of a single incident where someone got a vaccine and told me the next day, ‘Suddenly my face blew up.’” However, he noted that DIRs may be under-reported, as many patients, particularly those who experience a mild reaction, may not mention the reaction to a healthcare provider.

Similarity to Other Known Reactions

The reactions reported to date are similar to other delayed-type hypersensitivity reactions (DTRs), which have been noted in patients who underwent dental work, experienced illness, or received other vaccinations months after filler injections—in fact, the woman in the Moderna trial who experienced lip angioedema had a similar reaction after receiving an influenza vaccination in the past (Facial Plast Surg Aesthet Med. 2021;23:75-76).

Researchers are still working to understand the pathophysiology of DTRs, though it seems likely that immunologic triggers may cause a heightened immune reaction in some people. A 2015 retrospective review of 4,702 hyaluronic acid filler treatments found that 23 patients (0.5%) experienced delayed-onset nodules in the months following injection; nine of the 23 (39%) had an identifiable immunologic trigger such as flu-like illness before nodule onset (Dermatol Surg. 2015;41:929-939).

The filler is the nidus of the problem. If all else fails, you can dissolve the filler. It’s a process, but it should help almost every time.  —L. Mike Nayak, MD

Gilly Munavalli, MD, MHS, medical director and founder of Dermatology, Laser, & Vein Specialists of the Carolinas, in Charlotte, N.C., and an assistant professor of dermatology at Wake Forest School of Medicine, Winston-Salem, NC, said that the body essentially creates a subclinical granuloma around injected fillers.

“You’ve got a wall of inflammatory cells sitting around the filler, and the fillers continue to break apart into small hyaluronic acid chain molecules,” Dr. Munavalli said. “There’s a theory that those smaller molecules are more inflammatory,” and therefore more likely to respond to an immunologic trigger such as illness or vaccination.

Another theory posits that “fillers may act as adjuvants rather than direct T-cell activators, enhancing the antigen-specific immune response without triggering one of their own,” particularly in genetically predisposed individuals, including those with HLA subtypes B*08 and DRB1*03, with linkage to a predisposition for autoimmune or granulomatous disorders (Int J Women’s Dermatol. 2021;7:209-212).

Inflammatory reactions also have been reported following COVID-19 infection. A 2021 article by Dr. Munavalli and others included the case of a female patient who tested positive for COVID-19 15 days after receiving hyaluronic acid filler injections. Two weeks later, she reported “lips burning like sunburn and significant swelling to lips and cheeks and tear troughs.” Her primary care physician suspected a food allergy and treated her with intramuscular Kenalog. Her facial symptoms worsened, and the patient was subsequently treated with hyaluronidase, prednisone, and antibiotics over a period of weeks. The patient gradually experienced symptom resolution (Arch Dermatol Res [published online ahead of print February 9, 2021).

Effective Treatment Is Available

The same treatments that physicians have used for years to manage DIRs are effective in managing COVID-19 vaccine/dermal filler reactions. Some physicians are also using lisinopril, an angiotensin-converting enzyme (ACE) inhibitor, to treat DTRs related to COVID-19 or the COVID-19 vaccine, as the SARS-CoV-2 spike protein uses angiotensin-converting enzyme 2 (ACE2) to enter cells.

Treatment, however, isn’t always necessary. “‘Skillful neglect,’ as the English call it, is a real part of this treatment process,” Dr. Nayak said, noting that many reactions will resolve in a few days without intervention. If the reaction is causing the patient discomfort or distress, you may want to consider a tiered approach to treatment:

Over-the-counter medication. OTC antihistamines and anti-inflammatory pain medications such as ibuprofen are often sufficient to relieve patient discomfort, particularly when coupled with home remedies such as cold compresses, head-of-the-bed elevation, salt restriction, and alcohol avoidance, said Dr. Kourosh and Dr. Nayak. Dr. Nayak also sometimes recommends the use of arnica montana and bromelain, two dietary supplements that studies show may decrease edema and pain (Am J Ther. 2016;23:e184-197).

Because some journal articles suggest that nonsteroidal anti-inflammatory drugs (NSAIDs) might negatively affect vaccine efficacy, Dr. Munavalli said he doesn’t recommend NSAIDs as first-line treatment, while noting that typical doses of OTC NSAIDs “wouldn’t hurt, necessarily.” Indeed, a 2016 literature review found that the only studies that noted a “significant negative impact on immune response” were those in which NSAIDs were administered preventively at the time of vaccination, not when they were administered later to treat uncomfortable side effects (Hum Vaccin Immunother. 2016;12:2391-2402). A 2021 study found that NSAID treatment impaired the immune response of mice to SARS-CoV-2 infection (J Virol. 2021;95:e00014-21).

Steroids. The American Society for Dermatologic Surgery (ASDS) Guidance Regarding SARS-CoV-2 mRNA Vaccine Side Effects in Dermal Filler Patients, released in January 2021, states that “Delayed noninflammatory nodules without suspicion of infection may be treated initially with oral corticosteroids for 1 to 2 weeks, rather than dissolving with hyaluronidase, should the retention of the filler effect be desired. Addition of antibiotics (doxycycline or minocycline) should be considered for anti-inflammatory and antimicrobial properties.”

Dr. Kontis used a prednisone taper to successfully treat a woman who experienced facial swelling after her second dose of the Pfizer-BioNTech COVID-19 vaccine, which the patient received approximately eight months after receiving hyaluronic acid filler. Dr. Munavalli said that, in his experience, “Quite a few of these cases are not steroid-responsive anyway. … I’m not really sure why except that it may be that this reaction isn’t as sensitive to inhibition with steroids based on the mechanism of action.”

Antibiotics. The ASDS also recommends consideration of either doxycycline or minocycline. Dr. Nayak said he likes to use doxycycline treatment when it isn’t entirely clear whether a patient’s symptoms—redness, discomfort, and edema—are due to infection or inflammation. “Doxycycline is a nice choice because it’s anti-inflammatory as well as anti-infectant,” he said.

Lisinopril. Dr. Munavalli has published two articles about his experience using the ACE inhibitor lisinopril to proactively manage COVID-19 vaccine/dermal filler reactions (Arch Dermatol Res [published online ahead of print February 9, 2021]; JAAD Case Rep. 2021;10:63-68).

“Since high levels of the COVID-19 spike protein get into the skin and inactivate one of the checks and balances that keep angiotensin 2 under control, causing an inflammatory cascade, I postulated that treatment with an ACE inhibitor might interrupt that cascade and ease inflammation,” Dr. Munavalli said.

The first patient he treated with lisinopril was a 43-year-old woman who experienced significant intraorbital and perioral edema after receiving her second dose of the Pfizer-BioNTech COVID-19 vaccine. The swelling persisted despite treatment with cetirizine, and the patient refused corticosteroid treatment because she was concerned the steroids might blunt her immune response to the vaccine, so Dr. Munavalli prescribed 5 mg oral lisinopril. Within five hours, facial swelling had decreased, with a return to baseline in 24 hours.

An increased dose may be needed to treat resistant cases. “If a patient isn’t responding after a couple of days of treatment or their initial presentation is severe or uncomfortable, I have no problem starting at 10 milligrams, with the understanding that if we don’t see much of a response in a few days, we may need to try an even higher dose or consider other options,” Dr. Munavalli said.

In at least one documented instance, Dr. Munavalli used oral lisinopril as a prophylactic treatment before dose two of a mRNA COVID-19 vaccine. Lisinopril relieved the facial edema the patient experienced after her first dose of the Moderna vaccine, so Dr. Munavalli advised the patient to begin taking lisinopril (10 mg qd) two days prior to her second dose. The patient did and experienced only mild edema that resolved completely within 72 hours following her second shot (JAAD Case Rep. 2021;10:63-68).

Such low doses of lisinopril are unlikely to dramatically affect a patient’s blood pressure, but Dr. Munavalli advises patients to stand up slowly and watch for dizziness. If a patient is already on blood pressure medication, he consults with the patient’s internist before prescribing lisinopril.

Filler dissolution. If discomfort and edema persist despite home remedies, OTC, and prescription drug treatment, dissolution of the filler with hyaluronidase will resolve the problem. “The filler is the nidus of the problem,” Dr. Nayak said. “If all else fails, you can dissolve the filler. It’s a process, but it should help almost every time.”

More Efficient Interventions

The ASDS treatment guidance notes that the current recommendations depend on “observational studies of low certainty” and that “comparative studies of different management protocols would be invaluable but may be impractical because of the relatively small number of cases per institution. Therefore, prospective patient registries and multicenter collaborations are needed.” 

Inform patients that filler/vaccine reactions can occur years after filler injection and encourage them to report all unusual reactions after vaccination, even if their facial swelling, for instance, is mild and unlikely to require medical treatment. Report adverse events to the Vaccine Adverse Event Reporting System (VAERS), and consider reporting cutaneous reactions to COVID-19 vaccination to the American Academy of Dermatology Association’s COVID-19 Dermatology Registry.   

“Documentation of these reactions is really important,” Dr. Kontis said. “With this data, hopefully we can help more patients in the future.”

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Jennifer Fink is a freelance medical writer based in Wisconsin.