Immunogenicity Studies of Cosmetically Administered Nonanimal-stabilized Hyaluronic Acid Particles

Background: Hypersensitivity resulting from humoral or cellular immunologic mechanisms is the least well-documented of adverse events associated with dermal fillers.

Objective: Humoral and cellular immunogenicity of nonanimal-stabilized hyaluronic acid (NASHA) was studied in prospective clinical trials involving nasolabial fold augmentation.

Methods: In two randomized clinical studies, 150 (10 centers) and 283 (17 centers) subjects received NASHA as Restylane and/or Perlane (both QMed, Uppsala, Sweden; mean, 69 mg) for dermal augmentation. Serum immunoglobulin (Ig)E and IgG anti-NASHA were measured by immunoassay at 0, 6, and 24 weeks and IgE anti-NASHA by intradermal skin testing (ID-ST) at 0 and 24 weeks. The 24-week ID-ST site was biopsied 3 days later for histopathologic evidence of cell-mediated immunity.

Results: Of 433 subjects, 42 systemic adverse experiences were reported by 37 participants; all but 1 were judged by investigators to be unrelated to NASHA administration. All ID-STs and IgE anti-NASHA results were negative, indicating no IgE sensitization. Serologically, 91.8% of 425 subjects were negative for IgG anti-NASHA (<1.5 microg/mL) at all time points, whereas 7.8% had positive enrollment IgG anti-NASHA (range, 1.5-18.5 microg/mL) that remained essentially unchanged over the study period. The 24-week ID-ST biopsies showed no histological evidence for NASHA-induced cell mediated lymphocytic inflammatory reactions (Type IV hypersensitivity) or superficial dermal edema (Type 1 hypersensitivity).

Conclusion: NASHA administration does not elicit clinical/laboratory evidence for cellular or humoral immune responses in 98% of individuals, supporting the conclusion that Restylane and/or Perlane are not commonly immunogenic or allergenic.