A Case of Granulomatous Hypersensitivity Reactions to a Dermal Filler Precipitated by PD-1 Checkpoint Inhibitor Therapy

Abstract

Injection of filler material has become a routine procedure in dermatology practices in an attempt to improve the appearance of rhytides and prevent skin volume loss associated with aging. While the vast majority of injections are performed without complications, foreign body reactions may develop in 0.04-0.3% of individuals who receive fillers1. We recently encountered a 65-year-old woman with recurrent malignant melanoma who presented with a 2 month history of marked thickening of the skin along the sides of her face. She had been receiving nivolumab infusions for recurrent malignant melanoma and noted that these symptoms worsened after each infusion. She reported undergoing cosmetic procedures three years prior, one of which was an injection of a long-lasting dermal filler, polymethylmethacrylate microsphere enhanced bovine collagen (Bellafill). A biopsy of two areas revealed nodular infiltrates of histiocytes with small round lobules identified as polymethylmethacrylate microspheres. Based on clinical and histopathologic findings, a diagnosis of granulomatous dermatitis filler reaction was rendered. Nivolumab is a PD-1 checkpoint inhibitor that disrupts T-cell inhibitory pathways leading to increased immune activation. In this case, hyper-immune activation triggered a florid granulomatous reaction to the filler the patient had been injected with 3 years previously. This is a newly recognized side effect of PD-1 checkpoint immunotherapy and patients who are about to initiate such therapy should be warned about this potential complication.