Delayed Inflammatory Reactions to Hyaluronic Acid Fillers in a Patient Undergoing Dupilumab Therapy: A Case Report

BACKGROUNDDelayed inflammatory reactions to hyaluronic acid (HA) dermal fillers are uncommon but clinically significant, particularly in patients receiving immunomodulatory biologic therapies. Dupilumab, an interleukin-4 receptor alpha (IL-4Rα) inhibitor approved for chronic rhinosinusitis with nasal polyposis (CRSwNP) and other type 2 inflammatory conditions, has not been previously associated with this adverse event.

OBJECTIVETo report a case of delayed inflammatory filler reactions at previously injected hyaluronic acid filler sites associated with dupilumab administration, and to discuss proposed immunological mechanisms, differential diagnoses, and management considerations.

CASE PRESENTATIONA 34-year-old female with refractory CRSwNP, who had previously tolerated HA skinbooster injections without complications, developed facial warmth, pain, and hyperpigmented swelling at prior filler sites within 1 h of receiving her first dupilumab 600 mg dose. Within 24 h symptoms progressed to persistent bilateral cheek nodules. Similar, although to a lesser extent, reactions were observed after some of the later doses of dupilumab and treatment with hyaluronidase resulted in partial resolution. Reactions reappeared with additional dosing of dupilumab, requiring further doses of hyaluronidase to mitigate these reactions.

RESULTSScore on the Naranjo Adverse Drug Reaction Probability Scale: 8 (probable but not confirmed temporal correlation between dupilumab and inflammatory filler reaction). One possible mechanistic explanation is that dupilumab-mediated IL-4/IL-13 inhibition may shift ambient filler sites toward Th1/Th17-dominant immune activity; this hypothesis remains speculative without histopathological confirmation. Alternative diagnoses including infection, biofilm formation, and idiopathic granulomatous inflammation cannot be excluded.

CONCLUSIONTo our knowledge the first case report of delayed inflammatory filler reactions associated with biologic therapy. This potential interaction is important since it may expose patients who are on biologics to increased susceptibility to complications following esthetic procedures, and thus clinicians performing these esthetic treatments in these patients should be aware of this risk. This is constrained by the lack of imaging and biopsy investigation. More studies are necessary for understanding the mechanisms of this association and improving management strategies.

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