Recurrent Delayed Inflammatory Reaction After Dermal Filler Injection Treated With Intralesional 5-fluorouracil, Triamcinolone, and Hyaluronidase

Summary:

Infectious or biofilm-related inflammatory complications after dermal filler injection are uncommon but may be recurrent and challenging to manage. We report the case of a 44-year-old woman with recurrent erythema, tenderness, and induration in the right tear trough/infraorbital region after facial filler injection performed at an outside facility (reportedly hyaluronic acid, but the filler type was unverified). She had a normal temperature and normal routine laboratory test results. Because ultrasound suggested a small, immature fluid collection and the patient preferred conservative treatment, no incision and drainage was performed. She was treated with repeated intralesional injections of 5-fluorouracil, triamcinolone acetonide, and hyaluronidase. After multiple relapses despite prior systemic antibiotic therapy (details unavailable), repeated intralesional combination therapy achieved sustained clinical resolution. A localized contour depression was noted during follow-up. Intralesional 5-fluorouracil with triamcinolone and hyaluronidase may be a salvage option for refractory postfiller inflammatory complications with suspected infectious/biofilm involvement, particularly when conventional approaches are unsuccessful. Further studies are needed to define indications and optimal dosing.

Facial fillers may be complicated by inflammatory reactions,^1–5 and less commonly, infectious or biofilm-associated complications, which can present with localized erythema, edema, tenderness, and nodularity, and occasionally with fluid collections or abscess formation.^6,7 Most uncomplicated cases respond to appropriate systemic antibiotics or hyaluronidase when hyaluronic acid (HA) involvement is suspected.^2,4,7 However, some patients experience recurrent or treatment-refractory flares, in which diagnosis (infection versus delayed inflammatory nodule) and optimal management can be challenging. In this report, we describe a patient with a recurrent postfiller inflammatory flare with suspected infectious biofilm involvement and detail an intralesional combination approach using 5-fluorouracil, triamcinolone, and hyaluronidase as a salvage strategy.

CASE PRESENTATION

A 44-year-old woman presented with persistent swelling and tenderness in the right tear trough/infraorbital region. She reported having received facial filler injections at another medical facility involving the tear trough, nasolabial fold, and zygomatic region. According to the patient, the injected material was HA; however, the exact filler type, injection technique, and injected volume could not be verified because no procedural records were available. On examination, the affected area showed erythema and localized tenderness with a palpable indurated nodule. There was no increased local warmth, no fluctuation, and no purulent discharge. The patient denied systemic symptoms. Routine blood tests were within normal limits; C-reactive protein and erythrocyte sedimentation rate were not obtained. The patient reported multiple prior courses of systemic antibiotic therapy before referral; details regarding the antibiotic agents, dosing, and duration were unavailable. She had undergone several treatments at our hospital from January 24, 2024, to July 5, 2024, administered by another physician, with the precise medications not documented in the available records. Due to persistent or recurrent symptoms, she was referred to our department for further evaluation and management.

On July 14, 2024, intralesional injections were performed under sterile conditions using a 34G needle with a multiple-point technique in the superficial subcutaneous plane (estimated depth 3–4 mm). A total of 3.0 mL was injected, consisting of 5-fluorouracil (stock concentration, 25 mg/mL; diluted 1:6 with normal saline) combined with triamcinolone acetonide (stock concentration, 40 mg/mL; diluted 1:10 with normal saline). She re-presented on July 29, 2024, with worsening symptoms. Ultrasound demonstrated a small, superficial fluid collection suspicious for an early/immature abscess rather than a mature, drainable abscess. Clinically, there was no fluctuation or purulent discharge; the patient was afebrile, and routine blood test results were normal. Given the small and immature nature of the collection, the infraorbital anatomical location, and the patient’s preference for conservative management, incision and drainage were not performed, precluding microbiological culture.

On July 29, 2024, and at subsequent visits, a 3.0-mL intralesional mixture was injected using the same technique and plane. The mixture consisted of 1.0 mL of triamcinolone acetonide solution (stock concentration, 40 mg/mL; diluted 1:10; final concentration, 4 mg/mL; ~4 mg delivered), 0.5 mL of hyaluronidase solution (1500 U/vial reconstituted with 1 mL of normal saline and diluted 1:10; final concentration 150 U/mL; ~75 U delivered), and 1.5 mL of 5-fluorouracil solution (stock concentration, 25 mg/mL; diluted 1:6; final ~4.17 mg/mL; ~6.25 mg delivered). The entire 3.0-mL mixture was injected into the affected region using a fanning, multiple-point coverage pattern. Hyaluronidase was not used as monotherapy because inflammatory changes were already present, with ultrasound suggesting a small, early fluid collection; therefore, a combined intralesional approach was selected to address both a possible filler-related component and a suspected infectious/biofilm-associated inflammatory component.

The patient returned on August 5, August 14, September 11, and September 26, 2024, because of recurrent local inflammatory flares and was treated with the same July 29 regimen at each visit. On October 7, 2024, she again presented and was managed with the July 14 regimen (5-fluorouracil plus triamcinolone without hyaluronidase). She has remained free of further relapse since that time. The clinical course of the cutaneous lesions is illustrated in Figure 1, and the corresponding ultrasound findings are presented in Figure 2.

Fig. 1.

The patient is a 44-year-old woman. Representative clinical photographs of the right tear trough/infraorbital lesion demonstrating a recurrent, waxing-and-waning course. A, January 24, 2024: early documented flare with mild erythema and swelling of the right tear trough. B, August 5, 2024: recurrent induration and swelling involving the right infraorbital–malar area. C, September 26, 2024: follow-up after repeated intralesional treatments showing improvement of swelling and erythema with residual localized contour change (depression) at the prior lesion site.

Fig. 2.

The patient is a 44-year-old woman. On March 1, 2024, multiple heterogeneous hypoechoic areas were visible within the subcutaneous fat layer, extending from the inner canthus of the right eye to the zygomatic arch. Fluid movement was observed upon probe compression, and color Doppler flow imaging revealed abundant blood flow signals around the hypoechoic areas, raising suspicion for an immature abscess.

DISCUSSION

Complications after facial filler injection may present as delayed inflammatory reactions or, less commonly, as infection/biofilm-related inflammation. Accordingly, the differential diagnosis includes bacterial infection, early abscess formation, and noninfectious delayed inflammatory nodules/foreign-body reactions.^8–10

Initial management typically includes careful clinical assessment, targeted imaging when indicated, and systemic antibiotics when infection is suspected. When a mature, drainable abscess is present, aspiration or incision and drainage with microbiological studies is generally recommended, and treatment should be adjusted according to culture results. If HA involvement is suspected, hyaluronidase may be used as an adjunct to facilitate degradation of residual filler material and reduce ongoing inflammation. We agree that aspiration or drainage is appropriate when a clearly drainable collection is present; in our case, the collection was small and immature, without clinical fluctuation, and the patient preferred conservative management.

In the present case, microbiological confirmation was not obtained because drainage was deferred (small, immature collection in the infraorbital region and patient preference for conservative management). Therefore, we describe the condition as a suspected infectious (or biofilm-related) inflammatory complication rather than a definitive infection. The intralesional combination regimen was used as salvage therapy to address potential contributors, including fibroinflammatory modulation (5-fluorouracil), local anti-inflammatory effect (triamcinolone), and degradation of suspected HA filler (hyaluronidase), and was associated with sustained clinical improvement after recurrent flares.

Considerations for non-HA fillers and adverse effects are important. Although the injected material could not be verified, the patient reported receiving HA fillers, which is commonly used for tear trough and nasolabial fold augmentation; thus, hyaluronidase was included. Hyaluronidase would be expected to have limited or no direct effect on non-HA fillers (eg, poly-l-lactic acid or polymethylmethacrylate); in such cases, management should emphasize imaging, microbiological evaluation, drainage/debridement when indicated, and consideration of foreign material removal in refractory disease. A localized contour depression noted on follow-up may reflect corticosteroid-associated soft-tissue atrophy; to mitigate this risk, triamcinolone was diluted and delivered using a multiple-point superficial subcutaneous technique, avoiding deep fat or intramuscular deposition. Conservative observation is often appropriate, with delayed, minimal-volume filler correction or fat grafting considered if the contour defect persists after full resolution. Further studies are needed to clarify indications, dosing, and long-term outcomes.

CONCLUSIONS

Recurrent delayed inflammatory reactions after dermal filler injection can be difficult to manage. In this case, repeated intralesional injections of 5-fluorouracil, triamcinolone, and hyaluronidase were associated with sustained clinical improvement and may be considered as a salvage option in selected refractory cases.

DISCLOSURE

The authors have no financial interest to declare in relation to the content of this article.

PATIENT CONSENT

Written informed consent was obtained from the patient for participation in this case report and for publication of her clinical details and accompanying images.

ETHICAL APPROVAL

This case report was conducted in accordance with the principles of the Declaration of Helsinki (1964) and its later amendments. Formal ethics committee approval was waived by the ethics committee of Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, as this report describes a single case with no direct personal identifiers in the text.