Persistent, Intermitent Delayed Swelling PIDS intermitent swelling: late
                        adverse reaction to Hyaluronic Acid fillers

Cavallieri, Fernanda Aquino; Balassiano, Laila Klotz de Almeida; Bastos, Julien Totti de; Fontoura, Gabriela Helena Munhoz da; Almeida, António Bernardino de

doi:10.5935/scd1984-8773.201793931

Cited by 10 publications

(31 citation statements)

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“…DIR as a response to other viral vaccination has been reported sparsely in the literature. One report from Brazil detailed the characteristic induration, edema, and erythema of DIR in a patient in weeks following the administration of the influenza vaccine [20]. The author has personal experience with two patients experiencing DIR with calcium hydroxylapatite (Radiesse, Merz,Germany) filler treatment to the face and hands, respectively, following the first dose of administration of the shingles vaccine (author observation).…”

Section: Discussionmentioning

confidence: 99%

“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: 99%

“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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“…43 Additionally, the accompanying edema is the most visible after awakening and slightly improves throughout the day. 42,44,57 Some patients (~40%) developed accompanying systemic flu-like manifestations. 15 It is possible that those reactions may be related to contamination with DNA, proteins, bacterial endotoxins, even at much lower concentrations than HA.…”

Section: Epidemiologymentioning

confidence: 99%

“…42,44 The initiation of the reaction occurring as a result of an infection or injury leads to the increase in serum interferon, which may exacerbate previously present inflammations. 15,57,61 Furthermore, LMW-HA stimulates CD44 or TLR4 receptors on the surface of macrophages and dendritic cells. It activates them and delivers co-stimulatory signals to T cells.…”

Section: Epidemiologymentioning

confidence: 99%

“…15 The onset of a reaction is most commonly triggered by another infectious process (sinusitis, urinary tract infection, respiratory infection, dental infection), facial injury and dental procedures. 57 The response was also provoked by a vaccination and recurred with menstrual bleeding. 15,57 Each episode was probably due to an infectious triggering factor.…”

Section: Epidemiologymentioning

confidence: 99%

“…57 The response was also provoked by a vaccination and recurred with menstrual bleeding. 15,57 Each episode was probably due to an infectious triggering factor. Some authors also described a genetic predisposition underlying the reaction in individuals with the following subtypes: HLA B * 08 or DRB1 * 03.4 (a fourfold increase in the risk).…”

Section: Epidemiologymentioning

confidence: 99%

See 2 more Smart Citations

The Immunogenicity of Hyaluronic Fillers and Its Consequences

Owczarczyk‐Saczonek¹,

Zdanowska²,

Wygonowska³

et al. 2021

CCID

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Hyaluronic acid (HA) is a glycosaminoglycan, a natural component of the extracellular matrix. The identical structure of the molecule in all living organisms is its main advantage, as it translates into the minimal probability of immunogenicity. Therefore, it is the closest to the ideal preparation used as a filler, due to its biocompatibility and stability at the site of implantation. This paper includes the discussion of the potential mechanisms of adverse immune reactions to HA along with the mechanisms of reaction following vaccinations against SARS-CoV-2. Based on the literature, we tried to systematize adverse immune reactions with systemic manifestations to HA. The occurrence of unpredictable reactions to hyaluronic acid indicates that they may not be treated as neutral or non-allergenic. The modifications of the chemical structure of HA, additives and individual tendencies in a patient may be the cause of unpredictable reactions, leading to serious health consequences. Preparations of unknown origin, poorly purified, or including bacterial DNA are particularly dangerous. Therefore, long-lasting follow-up of the patient and the selection of a preparation approved by the FDA or EMA are of high importance. Patients are often unaware of the consequences of cheaper procedures performed by persons without suitable knowledge with the use of unregistered products, so the public should be educated and legal regulations should be introduced.

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Advantages of Sonography in Fillers and Complications

Cavallieri¹

2019

Image Guided Dermatologic Treatments

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Persistent, Intermitent Delayed Swelling PIDS intermitent swelling: late adverse reaction to Hyaluronic Acid fillers

Cited by 10 publications

References 0 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”

The Immunogenicity of Hyaluronic Fillers and Its Consequences

Advantages of Sonography in Fillers and Complications

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