Late Intervention Yet Successful Outcome with High-dose Pulsed Hyaluronidase for Forehead Filler Vascular Complication

Summary:

Vascular complications following hyaluronic acid filler injections are rare but may lead to ischemia and necrosis. Effective management often relies on the early administration of hyaluronidase to restore perfusion and prevent long-term damage. However, delayed presentations pose unique challenges due to prolonged ischemia and increased risk of tissue necrosis. A 35-year-old woman presented 3 days after forehead filler injection with signs of vascular compromise. Initial treatment with 1800 U hyaluronidase failed. On presentation, she exhibited advanced ischemia with erythema, pustules, and livedo reticularis. A high-dose pulsed hyaluronidase protocol totaling 32,000 U for 4 days was initiated. Rapid improvement followed, with complete epithelialization by day 30 and near-complete recovery by day 90 without scarring. Despite delayed presentation, the high-dose pulsed hyaluronidase protocol successfully reversed ischemia and prevented necrosis, supporting its use in late-stage vascular complications.

Hyaluronic acid (HA) fillers are a cornerstone in aesthetic medicine, widely used for their safety, reversibility, and effectiveness in facial rejuvenation and contouring. Despite their widespread use, adverse events such as vascular occlusion, though infrequent, pose significant risks, including tissue ischemia and necrosis.¹ Early recognition and intervention of vascular complications are critical to minimizing morbidity.²

The standard of care for managing such complications involves promptly administering hyaluronidase, an enzyme that degrades HA, to restore vascular patency and perfusion.³ However, in cases where intervention is delayed, such as this one, the prognosis is often guarded due to prolonged ischemia and the risk of irreversible tissue damage,⁴ and they are considered high risk with poor outcomes. Based on the CARE case report guidelines, this report highlighted a successful late intervention using high-dose pulsed hyaluronidase (HDPH), demonstrating efficacy beyond the commonly accepted treatment window.

PATIENT INFORMATION

A 35-year-old healthy woman underwent a cosmetic forehead HA filler (Juvéderm; Allergan, Inc.) injection using a blunt-tip cannula at another clinic. Immediately after the procedure, she experienced severe pain but did not seek any treatment on the same day. She noted discoloration from the nasal root to the scalp on day 2. She was administered 2 doses of 900 U hyaluronidase (total of 1800 U) at the original clinic without any clinical improvement, and ischemia continued to progress.

CLINICAL FINDINGS AND TIMELINE

By the third day, the patient developed well-demarcated erythema, worsening discoloration, and pustules in the affected area, prompting her to seek care at our clinic.

DIAGNOSTIC ASSESSMENT

On examination, a clear zone of erythema and livedo reticularis indicated advanced vascular compromise with impending skin necrosis (Fig. 1). Despite the delayed presentation, the urgency of the situation necessitated aggressive intervention.

Fig. 1.

Day 3 image, when the patient reported to our clinic, highlighting advanced vascular compromise with a well-demarcated zone of erythema, pustules, and livedo reticularis. This stage reflects impending necrosis due to sustained ischemia. Intervention with HDPH therapy was initiated on this day.

THERAPEUTIC INTERVENTION

HDPH therapy was initiated. On the first day of treatment at our clinic (day 3 after injection), 1500 U hyaluronidase was immediately administered, as the previous two 900-U doses did not give any improvement, followed by 1 additional dose of 1500 U and 1 dose of 3000 U later in the day (6000 U on day 3 after injection). During the subsequent 3 days, high doses were strategically administered: 5 doses of 3000 U each on day 4 after injection (total 15,000 U), 3 doses of 2200 U on day 5 after injection (total 6600 U), and 2 final doses of 2200 U (total 4400) on day 6 after injection. In total, 32,000 U hyaluronidase was used. (See table, Supplementary Digital Content 1, which displays the summary of HDPH protocol used. This table outlines the dosing regimen, frequency, and clinical rationale for each day of HDPH therapy administered to treat delayed-onset vascular compromise following forehead filler injection, https://links.lww.com/PRSGO/E295.) The injection doses in a day were spaced approximately 1 hour apart.

FOLLOW-UP AND OUTCOME

Despite the delayed initiation of treatment, the patient showed rapid improvement with hyaluronidase. The supporting treatment included cefcapene pivoxil as an oral antibiotic and loxoprofen and acetaminophen for pain relief. By the seventh day of the treatment course, a significant reduction in erythema and pustules was evident, with early signs of healing (Fig. 2). By day 30, complete epithelialization was achieved with minimal scarring (Fig. 3), and by day 90, the patient exhibited near-complete recovery with only subtle textural changes. At the 6-month follow-up (Fig. 4), the scar was barely perceptible, confirming the efficacy of the HDPH protocol, even if it started late. The patient was satisfied with the aggressive treatment approach and was pleased with the aesthetic recovery and outcome.

Fig. 2.

Day 7 image showing significant improvement after 4 days of aggressive HDPH therapy. Erythema has markedly reduced, pustules have resolved, and early signs of epithelialization are visible, indicating tissue recovery and restoration of perfusion.

Fig. 3.

Day 30 image showing complete epithelialization, further improvement in scar texture, and a significant reduction in discoloration. The healing process continues, with the scar becoming less noticeable and the skin returning to a more uniform appearance.

Fig. 4.

Day 180 image presenting near-complete resolution of scarring. Slight textural changes are visible on close examination, but the overall appearance of the forehead is greatly restored, with minimal residual effects of the vascular compromise.

DISCUSSION

This case highlighted the critical importance of aggressive and strategic management in addressing vascular complications resulting from HA filler injections, even when intervention is delayed. Vascular occlusion occurs when the injected material obstructs or compresses a blood vessel, leading to tissue ischemia. Filler-related vascular occlusion progresses through 5 clinical stages. It begins with pallor due to immediate arterial blockage, followed by livedo reticularis as deoxygenated blood pools in the venous network. Around day 3, pustules appear due to ischemic skin changes and bacterial overgrowth.⁵ If untreated, this advances to coagulative necrosis and, finally, devitalized tissue, presenting as slough or eschar, leading to significant morbidity and long-term aesthetic disfigurement.

Prompt administration of hyaluronidase, an enzyme capable of degrading HA, is widely recognized as the gold standard for managing such events. However, delayed presentations, as in this case, pose unique challenges, as prolonged ischemia can compromise tissue viability and increase the risk of permanent damage.⁶

The HDPH protocol offers a robust solution in such scenarios. Unlike traditional approaches involving low or single doses of hyaluronidase, the HDPH protocol involves administering high doses during multiple sessions.⁷ This method ensures sustained enzymatic activity to degrade the HA filler comprehensively, underscoring the necessity of substantial enzymatic intervention to reverse ischemia effectively.⁸

What sets this case apart is the success of the HDPH protocol despite the delayed initiation of treatment. Delayed presentations are often associated with a poorer prognosis due to the prolonged ischemia, which can lead to irreversible tissue damage.⁹ However, this case challenges the traditional understanding by demonstrating the protocol’s effectiveness in salvaging tissue integrity and preventing necrosis, even when treatment begins 3 days after occlusion. The progressive improvement observed in the patient—from significant reduction in erythema and pustules by day 7 to complete healing with minimal scarring by day 30—illustrates the HDPH protocol’s ability to limit damage, even in scenarios where ischemia has persisted for an extended period. Initial dose selection was based on clinical severity and anatomical extent, guided by the DeLorenzi guidelines and adapted based on daily response and resolution of ischemia signs (color return, warmth, and resolution of pustules) guided dose tapering.

The effectiveness of the HDPH protocol in this case can be attributed to several factors. First, the high doses of hyaluronidase ensure complete degradation of the obstructing HA filler, thereby rapidly alleviating vascular compression. Second, the pulsed administration allows for a sustained enzymatic effect, maintaining therapeutic activity for a prolonged period and maximizing the restoration of perfusion.⁷ Third, the protocol’s adaptability in terms of dosing and frequency enables tailored treatment based on the severity of ischemia and the patient’s response, as seen in this case where dosing was adjusted during the treatment course.

Furthermore, the ability of the HDPH protocol to prevent necrosis and limit tissue damage, even with a late start, has significant clinical implications. It underscores the importance of recognizing that vascular complications can still be managed effectively beyond the traditional window of immediate intervention.¹⁰ This experience expands the scope of salvageable cases and provides hope for patients who present late due to unrecognized complications or delayed access to care. In addition to its therapeutic benefits, the HDPH protocol reinforces the need for clinician preparedness and patient education. Clinicians should be well versed in the principles of the HDPH protocol, including its dosing strategies and escalation patterns, to ensure optimal outcomes.

This case highlighted the HDPH protocol’s ability to reverse ischemia and prevent necrosis and its potential to redefine treatment paradigms by demonstrating efficacy in delayed presentations. It also underscores the importance of escalating and aggressive interventions in delayed presentations and serves as a valuable addition to the body of evidence supporting HDPH therapy.

DISCLOSURES

No funding, grant, or support was received from any commercial, governmental, or nonprofit organization for the preparation, conduct, or publication of this work. All products, devices, and medications mentioned in this article were used as part of routine clinical practice, and no company or third party influenced the study design, treatment, analysis, or article preparation.

PATIENT CONSENT

Written informed consent for publication of photographs was obtained from the patient.