With delayed hypersensitivity reactions due to hyaluronic acid dermal filler procedures reported, issues on the safety of the injectable are newly recognized.

The known side effects of dermal fillers were acute complications such as blindness, necrosis or general edema, pain, and redness; however, there are possibilities of chronic complications such as “delayed hypersensitivity reactions,” suggesting the need for careful observation.

According to the Delayed Hypersensitivity Reaction to Hyaluronic Acid Dermal Filler Following Influenza-like Illness from the journal, Clinical, Cosmetic and Investigational Dermatology, 14 patients who had had dermal fillers between two to six times over the last four years reported redness, edema, and firm swelling followed by three to five days after they experienced flu-like symptoms. The delayed hypersensitivity reactions may arise between weeks to months, and the author concluded that it is impossible to predict the exact onset point.

Moreover, according to A Systematic Review of the Literature of Delayed Inflammatory Reactions After Hyaluronic Acid Filler Injection to Estimate the Incidence of Delayed Type Hypersensitivity Reaction published in 2020, although skin testing is not currently required, adverse events can be prevented with a pretreatment skin test especially since the number of filler procedures is increasing as well as the delayed hypersensitivity reactions.

Late-onset inflammatory response to hyaluronic acid dermal fillers, a journal published in 2017, reported that delayed hypersensitivity reactions occurred at least four to five months after procedures and 14 months for one patient. The author stated that foreseeing the complications of hyaluronic acid dermal fillers is impossible since symptoms differ depending on the manufacturers of the fillers and their production methods or skills.

The clinical papers from Kosin University College of Medicine in South Korea reported a case of side effects of a patient who had received dermal fillers twice at four-week intervals on the skin under the lower eyelids 18 months ago for aesthetic purposes. Asymptomatic reddish-brown blotch and edema occurred as delayed hypersensitivity reactions due to hyaluronic acid. Later, the symptoms improved by steroid injections, but biopsy presented hyaluronic acid remnant, suggesting a possibility of recurrence in the future.

Although the causes of hypersensitivity reactions followed by hyaluronic acid fillers are not accurately known, related research papers assume they may be the patient’s condition, injection method, certain components in hyaluronic acid, impurities added during the fermentation process, a small amount of bacterial protein, impurities added during the manufacturing process, and/or hydrolysis of cross-linked property.

“With filler procedures becoming popular, the number of patients experiencing delayed hypersensitivity reactions is also increasing. After a few months or years, procedure sites swell up or tuberous is felt, sometimes carrying erythema, fever, or pressure pain,” Dr. Jung-won, Shin from the department of dermatology, Seoul National University Hospital commented. The point is to be careful of not only acute but also chronic adverse events.

Many people believe that dermal fillers are safe, but from now on, it is significant to pay attention to their side effects despite the low incidence. “It is recommended to avoid having the procedure if you are allergic to the properties of the filler or if your procedure site has inflammation. The incidence of side effects rises if implants were in the procedure site or if fillers of different properties were used. Patients with bleeding disorders or autoimmune diseases, as well as those who take antiplatelet drugs or thrombolytic agents, should also be careful,” Dr. Shin emphasized.

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