Retrospective review of delayed adverse events secondary to treatment with a smooth, cohesive 20-mg/mL hyaluronic acid filler in 4500 patients

Humphrey, Shannon; Jones, Derek; Carruthers, Jean; Carruthers, Alastair; Beleznay, Katie; Wesley, Naissan O.; Black, Jeanette M.; Vanderveen, Sherri; Minokadeh, Ardalan

doi:10.1016/j.jaad.2020.01.066

Cited by 43 publications

(92 citation statements)

References 27 publications

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“…In the 400 subjects studied retrospectively, the authors did not report a DIR related to post viral illness or vaccination [21]. However, several studies have shown that the biphasic highlycrosslinked Juvederm vycross filler product line has a higher than expected rate of DIR [3,5,22]. It is has been reported Fig.…”

Section: Discussionmentioning

confidence: 95%

“…Comparatively, the incidence rate of hypersensitivity reactions to the monophasic NASHA fillers has been reported at 0.8%, with the rate for delayed reactions reported at 0.3%. Time to onset of delayed nodules ranged from 1 month to 3 years after HA implantation [3].…”

Section: Discussionmentioning

confidence: 99%

“…The literature details that a viral vaccine or illness can serve as a DIR triggering event. Published works have documented cases after viral illness [3,6,32,33]. Turkmani et al described 14 cases of HA DIR following an influenza-like illness [6].…”

Section: Discussionmentioning

confidence: 99%

“…Simultaneously, modifications in crosslinking agent technology over the last 10 years have rendered HA filler products more resistant to normal innate dermal enzymatic degradation processes, increasing longevity and decreasing dermal transit time [3]. Conceptually, HA fillers can be seen as long-lasting implants which can persist as long as 2-5 years or longer in certain facial anatomic areas such as the malar cheeks, midface, and tear trough, in varying levels of the dermis, subcutis, and supraperiosteum [4].…”

Section: Introductionmentioning

confidence: 99%

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“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”

et al. 2021

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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.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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“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”

et al. 2021

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“…Juvéderm Voluma XC is a new‐generation filler produced using Vycross (VYC) technology. Interestingly, with the introduction of the VYC technology, the incidence of delayed adverse events (DAE) has increased 1,2 . Recently, it has been reported and published that the incidence risk of DAE after VYC fillers is around 1.0% 3 .…”

mentioning

confidence: 99%

Delayed adverse events after using two different types of hyaluronic acid‐based dermal fillers

Han

Koh

Yoo

et al. 2020

Dermatologic Therapy

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New-generation dermal fillers-more differentiated and long-lastinghave been developed to maintain the lasting effects of HA fillers. Juvéderm Voluma XC is a new-generation filler produced using Vycross (VYC) technology. Interestingly, with the introduction of the VYC technology, the incidence of delayed adverse events (DAE) has increased. 1,2 Recently, it has been reported and published that the incidence risk of DAE after VYC fillers is around 1.0%. 3 We report a case of DAE to two new HA gels: Juvéderm Voluma XC and Dermalax Implant Plus.

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Juvéderm: What we know now

Shope

Andrews

Eason

et al. 2023

Dermatological Reviews

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Introduction: The Juvéderm family of dermal fillers are injectable, long‐lasting, homogenous, monophasic, monodensified hyaluronic acid fillers which are cross‐linked with varying amounts of 1,4‐butanediol‐diglycidyl‐ether (BBDE). Several formulations of Juvéderm exist, including the original Juvéderm Ultra® and Juvéderm Ultra Plus®, and the newer Juvéderm Voluma® XC. Differences in the Juvéderm product line stem from the hyaluronic acid (HA) concentration, gel hardness (G star (G*)), elastic properties (G prime (G′)), amount of molecular cross‐linking (BBDE percentage), and technology utilized for cross‐linking. Discussion: The Juvéderm filler lineup is such that each product is uniquely formulated for a specific indication. The lineup together has shown to be efficacious in treating superficial lines to deep‐seated wrinkles. These fillers are unlikely to cause adverse immune reactions, and as with other HAFs, their effects can be reversed with the injection of hyaluronidase. Conclusion: This chapter discusses the variety of fillers currently in the market within the Juvéderm family, as well as several new products on the horizon. We detail product FDA approvals, indications, safety, and adverse events.

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Retrospective review of delayed adverse events secondary to treatment with a smooth, cohesive 20-mg/mL hyaluronic acid filler in 4500 patients

Cited by 43 publications

References 27 publications

“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”

“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”

Delayed adverse events after using two different types of hyaluronic acid‐based dermal fillers

Juvéderm: What we know now

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