Migrating Granulomatous Chronic Reaction from Hyaluronic Acid Skin Filler (Restylane): Review and Histopathological Study with Histochemical Stainings

Abstract

Background: A unique case is presented in whom an allergic reaction to Restylane filler, associated with migrating granulomas, persisted despite medical interventions. A histopathological study was requested for evidence at court. Methods: Hematoxylin-eosin, alcian blue and colloidal iron staining were applied to skin sample biopsies obtained 5 months and 3 years after the hyaluronic acid (HA) injection. Results: The histological staining highlighted the presence of the filler inside the foreign body granuloma and in the derma of a biopsy obtained after 5 months; a small amount of filler was discovered within a granulomatous reaction 3 years after the injection. Conclusions: Smaller fragments of HA display inflammatory, angiogenic and immune-stimulatory activities. Intradermal skin testing before the start of HA filler therapy, and before each subsequent injection, may prevent legal implications for the plastic surgeon. Informed consent to skin tests should be obtained.

A multi‐center, open‐label, pilot study of allograft adipose matrix for the correction of atrophic temples

“…In contrast, adverse events are known to occur with all dermal fillers . Hyaluronic acid has been associated with necrosis, migrating granuloma, hypersensitivity, inflammation, and hyperpigmentation . Calcium hydroxylapatite has been linked to necrosis, filler displacement, and pain .…”

Local Injection of Hyaluronic Acid Filler Improves Open Gingival Embrasure: Validation Through a Rat Model

“…After 7 days of space opening, 20 μL of either phosphate‐buffered saline (PBS) (n = 10) or HA fillers (n = 10) was locally injected within the interdental papilla, ≈5 to 6 mm apical from the interdental papilla crest, using a 31‐gauge needle. A non‐cohesive (biphasic) and cross‐linked HA filler †† of non‐animal origin was used for the study because it was commercially available in an injectable form and its effects for dermal augmentation were previously reported 25‐27 . Morphologic changes of the interdental papilla were evaluated after 2 days.…”

Multiple oral granulomatous nodules to hyaluronic acid filler

“…Foreign body granulomatous reaction is a rare delayed complication that has been well documented elsewhere 2,5,6 . Also, migration of these inflammatory nodules has been described 6 .…”

“…Hyaluronic acid represents 78% of the dermal filler injections in the United States, 3 been the second most popular nonsurgical cosmetic procedure after botulinum toxin injection 4 . This popularity may be due to the fact that hyaluronic acid is a naturally occurring glycosaminoglycan present in many tissues within the human body, 5 while the polysaccharide used as a dermal filler is derived from fermented bacteria, it is cross‐linked to assure biocompatibility and stabilization, 6 which makes it minimally immunogenic.…”