COVID-19 and Dermal Fillers: Should We Really Be Concerned? / COVID y rellenos faciales ¿realmente debemos preocuparnos?

SARS-CoV-2 has caused millions of infections and deaths worldwide and case numbers continue to rise. Besides the effect of the virus on key organs - leading to respiratory illness, anosmia, diarrhea, and fever and other complications - delayed inflammatory reactions to hyaluronic acid dermal fillers, mainly in the face, have also been reported to occur after confirmed SARS-CoV-2 infections and in vaccinated individuals. While delayed inflammatory reactions tend to be self-limiting, they should be diagnosed and treated with corticosteroids, hyaluronidase, and/or antibiotics when necessary. The inflammation is generally not severe, yet these complications are classified as serious adverse events by the US Food and Drug Administration. They appear to be delayed type IV hypersensitivity reactions triggered by the immune system in the presence of SARS-CoV-2 or other viruses, such as those causing influenza, although the underlying mechanisms have not been fully elucidated. Because the longevity of dermal fillers is increasing, while the pandemic continues to evolve and new vaccines are under development, the long-term effects on hyaluronic acid fillers and other bioimplant materials should be studied. Physicians must also be encouraged to report these reactions, however mild, to ensure accurate records.

Facial Dermal Filler Injection and Vaccination: A 12-Year Review of Adverse Event Reporting and Literature Review.

BACKGROUND: Following authorization of 2 COVID-19 vaccines in December 2020, media attention increased towards postvaccine adverse events (AEs) in patients with facial dermal filler injections. OBJECTIVES: The purpose of this study was to characterize vaccine-related facial dermal filler AEs by scrutinizing the FDA's Manufacturer and User Facility Device Experience (MAUDE) database. METHODS: The MAUDE database was queried from January 1, 2011 to January 28, 2023 for facial dermal filler medical device reports (MDRs) discussing vaccination-related AEs. A PubMed (National Institutes of Health, Bethesda, MD) literature review on dermal filler AEs was then conducted. Data were analyzed with descriptive statistics. RESULTS: Of 10,637 MDRs identified, 33 were included. There were 25 MDRs (75.8%) related to COVID-19 vaccination. Hyaluronic acid-based fillers were described in 31 MDRs (93.9%). AEs were mostly reported within days postinjection (n = 7, 21.2%), but ranged from immediately (n = 2, 6.1%) to months (n = 6, 18.2%) postinjection. Most AEs were reported postvaccine (n = 17, 51.5%) vs postfiller (n = 14, 42.4%). In 26 reports (78.8%), AEs occurred at the site of filler injection. Most MDRs described inflammation/swelling (n = 21, 28.0%). The literature review returned 302 articles, of which 14 were included. Only 1 article (7.1%) was published in a plastic surgery journal. CONCLUSIONS: Although the pandemic brought attention to COVID-19 vaccine-related facial dermal filler AEs, this study shows a low incidence compared with the millions of vaccine and filler injections administered. Reactions with non-COVID-19 vaccines were also documented. Increased awareness may help providers counsel patients undergoing vaccination and dermal filler implantation.

Association between BNT162b2 vaccination and the development of delayed inflammatory reactions to hyaluronic acid-based dermal fillers-A nationwide survey.

BACKGROUND: Delayed inflammatory reactions (DIRs) to hyaluronic acid-based dermal fillers following COVID-19 vaccination has been reported in a few anecdotal reports and small series of cases. AIM: To evaluate the clinical characteristics, incidence, and management options relevant to BNT162b2 vaccination-associated DIR-A nationwide survey was conducted. METHODS: An online self-administered survey was sent to physicians who actively practice tissue filler injections. The data acquired included demographic and clinical characteristics of relevant DIR cases. RESULTS: Out of 262 responders, 20 cases with DIR following the vaccination were reported. 35% and 65% occurred shortly after the first and second vaccination dose, respectively. Overall, 65% of the DIRs appeared ≤5 days after vaccine administration and most DIRs resolved within 21 days. The filler's volume (p = 0.016) was associated with higher DIR severity, and the same tendency was noted among some filler types and locations of injection. Medical intervention was provided in 12 (60%) cases. CONCLUSION: DIR associated with BNT162b2 vaccination is rare and tends to resolve spontaneously or with short-term medical intervention.

Inflammatory immune-mediated adverse reactions induced by COVID-19 vaccines in previously injected patients with soft tissue fillers: A case series of 20 patients.

BACKGROUND: Adverse events (AE) after COVID-19 vaccines, particularly, but not solely, with those messenger RNA (mRNA)-based vaccines, have rarely been reported in patients previously treated with dermal fillers (DF). OBJECTIVE: To evaluate the morphology, clinical characteristics, the timing of presentation, and outcomes of inflammatory AE appeared in patients injected with DF, after anti-COVID-19 vaccination. METHODS: Descriptive study of a case series of 20 consecutive patients collected after the occurrence of AE in previously filled areas post COVID-19 vaccination. RESULTS: From January 2021 to July 2021, we analyzed 20 AE reactions triggered by COVID-19 vaccines in the previously mentioned cohort. They were vaccinated with Pfizer/Biontech (11; 55%), Moderna (5; 25%), Astra-Zeneca (3; 15%), and Sputnik (1; 5%). The most common manifestations were oedema/swelling, angioedema, erythema, skin induration, and granuloma. Less common reactions included myalgia and lymphadenopathy. In 13/20 (65%) cases, the AE appeared after the first dose of vaccine. These inflammatory AE appeared more rapidly after the second dose than after the first one. In 13/20 (65%) cases, the symptomatology subsided with anti-inflammatory/antihistaminic drugs, while spontaneously in 3/20 (15%). The manifestations are ongoing.in the remaining four cases (20%). CONCLUSION: Although probably rare, both RNA-based and adenovirus-based anti-COVID-19 vaccines can cause inflammatory bouts in patients previously treated with DF. In these cases, caution should be paid on subsequent vaccine doses, considering a tailored risk/benefit for any case before next vaccination.

A systematic review on COVID-19 vaccination and cosmetic filler reactions: A focus on case studies and original articles.

BACKGROUND: Tissue fillers are among the most popular cosmetic procedures performed and notably, cases of filler reactions after COVID-19 vaccination have been reported. OBJECTIVE: The objective was to determine the characteristics of patients with filler reaction after COVID-19 vaccination and address several considerations that have to be taken into practice. METHODS: A PRISMA compliant systematic search was conducted in Scopus, Web of Science, and PubMed/MEDLINE databases for articles published from inception up to October 21, 2021. RESULTS: Out of 106 initially retrieved articles, four of them were included in our study, and a total number of 13 cases were analyzed. In this study, we found that all of the patients who developed delayed-type reaction (DTR) following COVID-19 vaccination were middle-aged women without any known history of allergy to foods or drugs. All patients had a history of hyaluronic acid (HA) filler injection in their head and neck and demonstrated symptoms particularly swelling, from <1 day up to 10 days after the first or second doses of vaccines. Lisinopril, hyaluronidase, and corticosteroids seemed to have good results in management. CONCLUSION: Although rare, DTR to fillers after COVID-19 vaccination can happen. Physicians should be aware of the pathogenesis and management of this phenomenon.

Hyaluronic acid delayed inflammatory reaction after third dose of SARS-CoV-2 vaccine.

BACKGROUND: Treatments based on hyaluronic acid represent one of the most largely used practice of esthetic medicine. In the literature, it has already been described delayed reaction after vaccine like flu vaccine mediated by T-lymphocytes. AIM: We report three cases of dermal filler reactions following mRNA vaccination against SARS-CoV-2; all the patients had received the filler months or even years before the vaccine. PATIENTS: Patient one: A 60-year-old female patient that was treated one year ago in the lip developed swelling days after getting mRNA Pfizer Biotech vaccine. She received her booster of Pfizer vaccination one week before. Patient two: A 45-year-old female patient treated in the lip two years before developed angioedema days after getting her booster of Pfizer Biotech vaccine. In this case, it was necessary to prescribe cortisone per os. Patient three: A 40-year-old female patient treated for the nasolabial fold five months before developed erythema and edema after receiving the booster of Moderna Vaccine. RESULTS: As demonstrated in our three case reports, even the booster of vaccine can cause delayed inflammatory reactions in patients that have previously received fillers. CONCLUSION: Delayed inflammatory reactions in patients that have received filler in the past are uncommon and usually self-limited. Those are the first example reported in the literature of reaction after the booster dose without any previous symptoms.

Increase in the incidence of acute inflammatory reactions to injectable fillers during COVID-19 era.

BACKGROUND: Acute inflammatory reactions (AIRs) are a rare complication following esthetic treatment with hyaluronic acid (HA) and/or human collagen fillers. However, a substantial increase in the frequency of AIRs was observed in the first author's clinic since May 2020. AIMS: To report AIR cases, we experienced and discuss potential underlying mechanisms. METHODS: This was a retrospective review of patients representing AIR symptoms following filler injection with HA or human collagen in our clinic. RESULTS: Although only one case of an AIR with an incidence rate of 0.01% was recorded following filler treatment between September 2008 and April 2020 in our clinic, we observed 14 AIR cases without anaphylaxis, with an incidence rate of 1.18% between May 2020 and June 2021, in line with the spreading of the new coronavirus pandemic. All cases were females aged 40-57 years, and the time of onset was within hours after filler injection. Three patients had been treated with HA fillers only, 2 with HA plus human collagen, and 9 with human collagen only. Most patients had been treated with these products in the past. Nine patients were treated with oral prednisolone. In all cases, symptoms resolved entirely within a week without sequelae. CONCLUSIONS: The marked increase in AIRs coincided with the COVID-19 pandemic. Possible explanations include immune system alterations caused by extensive changes in domestic and personal hygiene, prolonged and elevated stress levels, and subclinical COVID-19 infection. Further studies may be warranted.

Hyaluronic acid soft tissue filler delayed inflammatory reaction following COVID-19 vaccination - A case report.

BACKGROUND: The use of hyaluronic acid soft tissue fillers in aesthetic medicine exploded in recent years for many reasons, including being relatively safe. Incidence of delayed inflammatory reactions (DIRs) to hyaluronic acid soft tissue fillers range between 0.3% and 4.25%. These reactions are mediated by T-lymphocytes and can be triggered by flu-like illnesses, including SARS-CoV-2 infection. Vaccination may also induce hypersensitivity. AIM: In this case report, we present two cases of delayed reaction after hyaluronic acid soft tissue filler treatment of the tear trough area and following mRNA vaccination against SARS-Cov-2, also known as COVID-19, months later. PATIENTS: A 39-year old female who previously had her tear trough area treated with hyaluronic acid soft tissue filler developed swelling days after getting the mRNA Pfizer-BioNTech COVID-19 vaccine. Another patient, a 61-year-olf female, developed intermittent facial swelling in areas previously treated with hyaluronic acid soft tissue fillers days after receiving her first dose of the mRNA Pfizer-BioNTech COVID-19 vaccine. RESULTS: As demonstrated in our case report, vaccination against COVID-19 may induce DIRs in patients who previously had hyaluronic soft tissue fillers. CONCLUSION: Delayed inflammatory reactions to hyaluronic acid soft tissue fillers are uncommon and usually self-limited, with frequent spontaneous resolution. However, considering the ongoing pandemic and the worldwide demand for vaccines against COVID-19, the aesthetic providers should be conscious of the risks posed by the interaction of such vaccines in patients who previously had or seeking hyaluronic acid soft tissue filler injections.

Hypersensitivity reaction to Hyaluronic Acid Dermal filler following novel Coronavirus infection - a case report.

The incidence of hypersensitivity reactions to hyaluronic acid dermal fillers is between 0.3 and 4.25%, mediated by T-lymphocytes. Flu-like illness can trigger immunogenic reactions at the site of filler placement. Cases of SARS-CoV-2 are significant and pose a possible risk of inducing hypersensitivity. This case report is of a delayed-type hypersensitivity after hyaluronic acid dermal filler treatment of the nose and subsequent infection with SARS-CoV-2. Risk factors for the development of such symptoms were identified as the presence of hyaluronic acid combined with flu-like illness and repeated treatment of one area. The case resolved without intervention. Clinicians should be mindful of the risk posed by the interaction of hyaluronic acid dermal filler with SARS-CoV-2 in light of the pandemic.

"COVID-19/SARS-CoV-2 virus spike protein-related delayed inflammatory reaction to hyaluronic acid dermal fillers: a challenging clinical conundrum in diagnosis and treatment".

We present the first reported cases of delayed inflammatory reactions (DIR) to hyaluronic acid (HA) dermal fillers after exposure to the COVID-19 spike protein. DIR to HA is reported to occur in the different scenarios including: secondary to poor injection technique, following dental cleaning procedures, following bacterial/viral illness, and after vaccination. In this report of 4 cases with distinct clinical histories and presentations: one case occured following a community acquired COVID-19 infection, one case occured in a study subject in the mRNA-1273 clinical phase III trial, one case occurred following the first dose of publically available mRNA-1273 vaccine (Moderna, Cambridge MA), and the last case occurred after the second dose of BNT162b2 vaccine (Pfizer, New York, NY). Injectable HA dermal fillers are prevalent in aesthetic medicine for facial rejuvenation. Structural modifications in the crosslinking of HA fillers have enhanced the products' resistance to enzymatic breakdown and thus increased injected product longevity, however, have also led to a rise in DIR. Previous, DIR to HA dermal fillers can present clinically as edema with symptomatic and inflammatory erythematous papules and nodules. The mechanism of action for the delayed reaction to HA fillers is unknown and is likely to be multifactorial in nature. A potential mechanism of DIR to HA fillers in COVID-19 related cases is binding and blockade of angiotensin 2 converting enzyme receptors (ACE2), which are targeted by the SARS-CoV-2 virus spike protein to gain entry into the cell. Spike protein interaction with dermal ACE2 receptors favors a pro-inflammatory, loco-regional TH1 cascade, promoting a CD8+T cell mediated reaction to incipient granulomas, which previously formed around residual HA particles. Management to suppress the inflammatory response in the native COVID-19 case required high-dose corticosteroids (CS) to suppress inflammatory pathways, with concurrent ACE2 upregulation, along with high-dose intralesional hyaluronidase to dissolve the inciting HA filler. With regards to the two vaccine related cases; in the mRNA-1273 case, a low dose angiotensin converting enzyme inhibitor (ACE-I) was utilized for treatment, to reduce pro-inflammatory Angiotensin II. Whereas, in the BNT162b2 case the filler reaction was suppressed with oral corticosteroids. Regarding final disposition of the cases; the vaccine-related cases returned to baseline appearance within 3 days, whereas the native COVID-19 case continued to have migratory, evanescent, periorbital edema for weeks which ultimately subsided.

Why we should be avoiding periorificial mimetic muscles when injecting tissue fillers.

BACKGROUND: Tissue fillers are generally safe and well tolerated by patients. However, complications do occur and may be very severe, such as intravascular injection (with occasional residual tissue loss, visual and neurological sequelae) and late nodularity and swelling. Methods to lessen the likelihood of complications have been the subject of much recent literature. Depth of injection has been identified as a key safety consideration. PATIENTS/METHODS: The role of injection of facial filler into the muscular layer of the face is explored in this article. Literature was explored using available search facilities to study the role of injections in or around this layer in the production of significant adverse reactions. RESULTS: A body of literature seems to suggest that injection into mimetic musculature of the face especially the musculature in the periorbital and perioral regions is prone to adverse reactions. CONCLUSIONS: Injection of agents into the perioral and periorbital mimetic muscular layer may produce, product clumping, displacement, and tendency to late nodularity and swelling. It also risks intravascular injection as compared to injection of other layers of the face. Injection into the mimetic muscles especially the sphincteric muscles should be avoided to minimize the risk of complications.