A Systematic Review of the Literature of Delayed Inflammatory Reactions After Hyaluronic Acid Filler Injection to Estimate the Incidence of Delayed Type Hypersensitivity Reaction.

Background: Hyaluronic acid (HA) dermal filler injection is believed to be a safe procedure. However, with the increase in the number of performed procedures and indications, the number of product-related complications, especially delayed inflammatory reactions, has also increased. Delayed-type hypersensitivity (DTH) reaction is one of these delayed inflammatory reactions, which is preventable by performing a pretreatment skin test.

Objectives: The authors sought to find the incidence of delayed inflammatory reactions and DTH reaction after HA injection and to determine whether a pretreatment skin test is worthwhile to be performed.

Methods: The authors conducted a systematic literature review of all the relevant prospective studies, retrospective studies, and case reports on delayed inflammatory reactions and DTH reaction after HA filler injection.

Results: The incidence of delayed inflammatory reactions calculated from the prospective studies was 1.1% per year, and that of possible DTH reaction was 0.06% per year. Most retrospective studies estimated a percentage of delayed inflammatory reactions of less than 1% in 1 to 5.5 years. The incidence of DTH reaction would be lower than that. Among all the DTH cases reported, only about 5% of them were proven to be genuine DTH reactions.

Conclusions: The incidence of both delayed inflammatory reactions and DTH reaction is low. There is evidence that genuine DTH reactions caused by HA fillers approved by the Food and Drug Administration do exist. This adverse event can be prevented by performing a pretreatment skin test. However, the incidence of DTH reaction is so low that the pretreatment skin test is not mandatory if Food and Drug Administration-approved HA fillers are used.