Researchers detail a case of recurrent inflammation at previous hyaluronic acid filler sites following treatment with the biologic.
Dupilumab may trigger delayed inflammatory reactions at sites of previous hyaluronic acid filler injections, according to what researchers say is the first published case linking the biologic to the complication.
The case, published in the Journal of Cosmetic Dermatology, involved a 34-year-old woman with refractory chronic rhinosinusitis with nasal polyps who had previously received several hyaluronic acid skin-booster treatments without adverse events.
Her most recent treatment involved 1mL of a lightly cross-linked, low-viscosity hyaluronic acid formulation injected intradermally into each cheek.
About one hour after receiving her first 600mg loading dose of dupilumab, she developed facial warmth, pain, and erythematous swelling precisely at the sites of her previous filler injections.
Over the following 24 hours, palpable papules and nodules developed at individual injection points that progressed into firm, persistent nodules across both cheeks. A similar but less severe reaction occurred after her second 300mg dose of dupilumab.
“On September 3, 2024, the patient presented to our clinic for evaluation of persistent bilateral malar nodules, more prominent on the right side,” the researchers wrote.
“She did not seek medical attention after the initial episode because the symptoms partially improved without intervention.
“However, after the reaction recurred following her second dupilumab dose and the nodules persisted and became more conspicuous, she sought further evaluation.”
When the patient presented for assessment, examination showed firm, mildly tender nodules at the previous filler sites, but no erythema, fluctuance, drainage, fever, or other evidence of systemic infection.
Clinicians suspected an inflammatory reaction to residual filler and treated her with 150 units of hyaluronidase, resulting in a marked reduction in nodule size within five days.
Systemic corticosteroids were considered but deferred because the diagnosis remained presumptive, while antibiotics were withheld in the absence of clinical signs of infection.
Antihistamines were also not used because the presentation was considered inconsistent with an immediate IgE-mediated hypersensitivity reaction.
The inflammatory reaction recurred after a third dupilumab dose and was again treated with hyaluronidase, with further reduction in the nodules over the following week.
The patient’s score of eight on the Naranjo Adverse Drug Reaction Probability Scale indicated a probable, but not definitive, association between dupilumab and the inflammatory filler reaction.
“Dupilumab may have caused a delayed inflammatory reaction (DIR) at the locations of previous hyaluronic acid (HA) filler injection through a number of different mechanisms,” the researchers wrote.
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“The immunologic tolerance that had previously maintained a state of inactivity surrounding residual HA filler material was disturbed by dupilumab-mediated suppression of IL- 4 and IL-13, which is the most acceptable hypothesis.”
They said the repeated recurrence after dupilumab dosing and improvement after enzymatic dissolution of the filler supported this hypothesis, although the mechanism remained speculative in the absence of histological or microbiological evidence.
Delayed reactions to hyaluronic acid fillers can occur weeks to months after treatment and typically present as tender erythematous swelling or persistent nodules.
Previous reports have also described inflammatory filler reactions following systemic immune stimuli including zoledronic acid and Shingrix and Fluzone vaccination.
The researchers stressed that the case could not establish causality. No ultrasound, biopsy, histopathology, or microbiological culture was performed, meaning infection, bacterial biofilm, a spontaneous delayed filler reaction, and idiopathic granulomatous inflammation could not be definitively excluded.
They recommended that future suspected biologic-associated filler reactions undergo imaging and tissue sampling where feasible.
“To our knowledge, this is the first published case report describing this specific interaction,” the researchers wrote.
“The evidence in this case is constrained by the absence of imaging and histopathological investigation, and the causal relationship between dupilumab and the observed reactions remains probable rather than confirmed.
Despite the limitations of their study, they said the case highlighted a need for increased clinician awareness and consideration of potential interaction between biologic therapies and previously placed HA fillers.
“Patients receiving immunomodulatory treatments with a history of HA filler injections should be counselled on such rare potential risks,” they concluded.
“Prospective studies elucidating the immunological underpinning of this interaction and mechanistic studies are needed to inform evidence-based management recommendations.”
