CC BY 4.0 · Arch Plast Surg 2024; 51(01): 020-026
DOI: 10.1055/a-2184-6554
Review Article

Etiology of Delayed Inflammatory Reaction Induced by Hyaluronic Acid Filler

Won Lee
1   Yonsei E1 Plastic Surgery Clinic, Scientific Faculty of the Minimal Invasive Plastic Surgery Association, Dongan-ro, Dongan-gu, Anyang, Republic of Korea
Sabrina Shah-Desai
2   Perfect Eyes Ltd, London, United Kingdom
Nark-Kyoung Rho
3   Department of Dermatology, Sungkyunkwan University School of Medicine, Gyeonggi-do, Republic of Korea. Leaders Aesthetic Laser & Cosmetic Surgery Center, Seoul, Republic of Korea
Jeongmok Cho
4   Etonne Plastic Surgery Clinic, Scientific Faculty of the Milimal Invasive Plastic Surgery Association, Seoul, Republic of Korea
› Author Affiliations
Funding None.


The etiology and pathophysiology of delayed inflammatory reactions caused by hyaluronic acid fillers have not yet been elucidated. Previous studies have suggested that the etiology can be attributed to the hyaluronic acid filler itself, patient's immunological status, infection, and injection technique. Hyaluronic acid fillers are composed of high-molecular weight hyaluronic acids that are chemically cross-linked using substances such as 1,4-butanediol diglycidyl ether (BDDE). The mechanism by which BDDE cross-links the two hyaluronic acid disaccharides is still unclear and it may exist as a fully reacted cross-linker, pendant cross-linker, deactivated cross-linker, and residual cross-linker. The hyaluronic acid filler also contains impurities such as silicone oil and aluminum during the manufacturing process. Impurities can induce a foreign body reaction when the hyaluronic acid filler is injected into the body. Aseptic hyaluronic acid filler injections should be performed while considering the possibility of biofilm formation or delayed inflammatory reaction. Delayed inflammatory reactions tend to occur when patients experience flu-like illnesses; thus, the patient's immunological status plays an important role in delayed inflammatory reactions. Large-bolus hyaluronic acid filler injections can induce foreign body reactions and carry a relatively high risk of granuloma formation.

Authors' Contributions

Conceptualization and writing: W.L.; Review, editing, and supervision: S.S-D., N-K.R., and J.C. All authors have read and agreed to the published version of the manuscript.

Publication History

Received: 03 June 2023

Accepted: 26 August 2023

Accepted Manuscript online:
29 September 2023

Article published online:
07 February 2024

© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (

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