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

Abstract

Injection of filler material has become routine in dermatology in improving the appearance of rhytides and increasing skin volume associated with aging.  While the vast majority of injections are accomplished without complications, foreign body reactions may develop in a certain percentage of individuals. We recently encountered a 65-year-old woman with recurrent malignant melanoma who presented with marked thickening along the sides of her face for approximately 2 months. She recently received  nivolumab infusions for recurrent malignant melanoma and noted that symptoms worsened after each infusion. She reported having had cosmetic procedures done 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 recognizable 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, the immune activation triggered a florid granulomatous reaction to the filler the patient had been injected with 3 years previously. We present this case as the second report of this phenomenon and the first in the dermatologic literature. This is a newly recognized side effect of PD-1 checkpoint immunotherapy and patients who are about to initiate such therapy who have had filler injections should be warned about this potential complication.