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 augumentation. 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 (