Document | Latin American Journal of Clinical Sciences and Medical Tecnology

Case Report

Jonathan Garrido Cruz^a.
^aHospital Español, Mexico City, Mexico.
Corresponding Author: , . Telephone number: ; e-mail: dr.jonathan.garrido@gmail.com

Citation: Garrido Cruz J. Treatment of Frontal Cutaneous Necrosis Secondary to Hyaluronic Acid Application: An Effective Approach Based on Molecular Biology.
Lat Am J Clin Sci Med Technol. 2025 May;7:42-46.
Received: April 22^nd, 2025.
Accepted: May 28^th, 2025.
Published: May 30^th, 2025.
Views: 1025
Downloads: 4

DOI
https://doi.org/10.34141/LJCS1455722

ABSTRACT

Background. Hyaluronic acid (HA) fillers are widely used in aesthetic medicine due to their biocompatibility and safety profile. However, complications such as vascular occlusion leading to tissue necrosis, although rare, pose significant clinical challenges. This case report presents an innovative treatment protocol for managing frontal necrosis following the injection of HA filler. Case Presentation. A 45-year-old male developed frontal necrosis 72 hours post-injection with HA filler. The protocol included careful debridement, targeted hyaluronidase application, and the use of hybrid cooperative complexes of HA (Profhilo^®) for tissue regeneration. The patient underwent a structured treatment plan, achieving complete reepithelialization by day eight, with minimal residual scarring and excellent aesthetic outcomes. Conclusions. The combined use of hyaluronidase and Profhilo^®, along with a standardized injection technique, demonstrated efficacy in resolving necrotic complications and restoring tissue integrity. This case highlights the importance of early intervention, evidence-based protocols, and emerging technologies in aesthetic medicine.

Keywords: hyaluronic acid, vascular occlusion, necrosis, hyaluronidase, Profhilo®, aesthetic medicine, tissue regeneration

RESUMEN

Antecedentes. Los rellenos de ácido hialurónico (AH) se usan ampliamente en medicina estética debido a su biocompatibilidad y perfil de seguridad. Sin embargo, las complicaciones como la oclusión vascular que derivan en necrosis tisular, aunque raras, representan retos clínicos significativos. Este reporte de caso presenta un protocolo innovador para tratar la necrosis en la frente después de una inyección de relleno de AH. Presentación del caso. Masculino de 45 años de edad que presentó necrosis en frente después de 72 horas de haber recibido una inyección de relleno de AH. El protocolo incluyó desbridamiento cuidadoso, aplicación dirigida de hialuronidasa y uso de complejos cooperativos híbridos de AH (Profhilo^®) para lograr regeneración tisular. El paciente se sometió a un plan de tratamiento estructurado mediante el cual logró re-epitelización completa para el día ocho, con mínima cicatrización residual y excelentes resultados estéticos. Conclusiones. El uso combinado de hialuronidasa y Profhilo^®, junto con una técnica de inyección estandarizada, demostró eficacia para resolver las complicaciones necróticas y reparar la integridad tisular. Este caso clínico resalta la importancia de la intervención temprana, protocolos basados en evidencia y las nuevas tecnologías en medicina estética.

Palabras clave: ácido hialurónico, oclusión vascular, necrosis, hiaruronidasa, Profhilo®, medicina estética, regeneración tisular

INTRODUCTION

Hyaluronic acid (HA) dermal fillers are a prominent option for minimally invasive procedures in aesthetic medicine.

Due to HA's biodegradable and biocompatible nature, these products have a favorable safety profile. However, the increasing use of HA fillers has led to a higher incidence of complications, ranging from mild and transient reactions to severe adverse effects, such as vascular occlusion.

Proper medical training, knowledge of correct injection techniques, a solid understanding of facial anatomy and HA filler rheology, and the use of products with maximum purity and minimal tissue impact are essential to minimize these risks.¹

Complications are classified as immediate or delayed. Immediate reactions are

redness,
swelling,
pain,
and bruising at the injection site.

They are common and typically resolve spontaneously. However, more severe complications, such as vascular occlusion, carry the risk of tissue necrosis.

A study on vascular complications associated with HA fillers estimates an incidence of 0.001% to 0.01%. Rapid identification and treatment of these complications are essential to prevent irreversible sequelae.²

Delayed complications include the formation of nodules, granulomas, and immunological reactions, which may occur weeks or even months after treatment. These responses are often more challenging to manage and frequently require the use of hyaluronidase or corticosteroids.

Infections, although rare, can arise if strict aseptic protocols are not followed during the procedure.

Proper technique and timely intervention are key to preventing and managing complications, highlighting the importance of sharing clinical cases and publishing resolution techniques for such events.³

Recommendations in the literature for treating necrotic lesions caused by HA fillers include

immediate application of hyaluronidase,
warm compresses,
vasodilators (both topical and systemic),
low-dose aspirin administration,
and hyperbaric oxygen.⁴

Profhilo^® is a product based on hybrid cooperative complexes of HA (HCC) developed using patented NAHYCO^® hybrid technology, a thermal production process. This process combines high-molecular-weight HA (1100-1400 kDa) and low-molecular-weight HA (80-100 kDa).

The HCC is stabilized through a thermal process that does not use cross-linking agents. The final product is designed to facilitate tissue bioremodeling. Low-molecular-weight HA activates the CD44 receptor, stimulating the natural production of HA, collagen, and deep hydration. Meanwhile, high-molecular-weight HA provides support, improves skin firmness, and directly stimulates fibroblasts to enhance collagen and elastin production.

Profhilo^® diffuses and integrates easily into extracellular matrix tissues.

In aesthetic medicine, HCCs treat skin laxity and improve skin quality through cellular bioremodeling.^5,6

The application protocol for HCCs is standardized and involves two sessions at 30-day intervals. Each session administers 64 mg of HA in 10 intradermal boluses of 0.2 ml each, using a prefilled 2 ml syringe.

Injection points on the face are standardized into five specific points per side, known as bioesthetic points (BAP).⁷

This case report aims to raise awareness about preventing and properly managing complications resulting from HA filler use, presents a technique for resolving necrotic lesions involving hyaluronidase (HCC), and appropriate debridement procedures.

Case Report: Frontal Necrosis Post-Hyaluronic Acid Injection

Initial Assessment and Background

A 45-year-old male patient with no relevant medical history underwent an aesthetic procedure involving hyaluronic acid injection (Belotero Volume) into the forehead, in the midline, 2 cm above the glabella.

Within 72 hours of the procedure, he experienced intense pain, cutaneous necrosis, and ischemic signs in the treated area.

The patient presented with a visible necrotic lesion and significant aesthetic compromise, as well as with local pain and swelling, which was managed successfully using a regenerative protocol (Photograph 1).

Photograph 1. Visit 1
Deep central necrotic lesion

Detailed Description of Lesions

Location

Central glabellar region and upper forehead.

Characteristics

Central necrosis. Black, dry, necrotic skin indicates deep tissue damage, characterized by a depressed appearance compared to the surrounding tissue.
Perilesional ischemia. Violaceous-gray discoloration indicates vascular compromise.
Inflammatory margins. Surrounding erythematous tissue with signs of active inflammation.
Edema. Mild swelling extending periocularly.
Skin texture. Dry and rough over necrotic areas; tense over ischemic zones.

TREATMENT PROTOCOL

Careful Debridement

Method

Conservative removal of necrotic tissue with a #15 blade and curette, ensuring no viable tissue was affected.

Preparation

The area was disinfected with 2% chlorhexidine and povidone-iodine.

Outcome

Necrotic tissue was removed without compromising viable tissue, preparing the site for hyaluronidase application.

Hyaluronidase Application

Product and Dose

1 ml of Total Corrector^® hyaluronidase (pbserum^®), injected into subdermal and perilesional areas.

Technique

A 30G needle was used for bolus and retrograde injections, targeting the glabellar base and lesion margins to dissolve remaining filler and restore perfusion.

Profhilo^® Application

Technique

Ten intralesional microinjections (0.01 ml each) at the lesion’s edge
Ten perilesional microinjections at 1.5 mm intervals
Ten more microinjections in the glabellar base to enhance vascularization
Sterile dressing; a 0.5 ml Profhilo^®-impregnated dressing was applied

Pharmacological Management

Antibiotics: clindamycin (600 mg q8 h) and metronidazole (500 mg q 12 h)
Anti-inflammatory: ibuprofen (400 mg q 8 h for 5 days)
Microcirculation: acetylsalicylic acid (150 mg q 8 h for 3 days)

Clinical Evolution and Outcome

The treatment was performed over 20 days, involving seven visits (Table 1).

Table 1. Evolution by day
Visit	Time	Lesion Evolution and Management
1^st	72 hours post-procedure	Initial necrosis was noted in the glabellar and forehead areas with ischemia. Debridement and hyaluronidase were administered. Intralesional and perilesional Profhilo^® applied.

2^nd	48 hours later	Marked reduction in erythema and inflammation. Skin texture improvement. Repeat Profhilo^® application and sterile dressing placement.

3^rd	72 hours post-2^nd visit	Necrotic lesion reduced in size with early reepithelialization. No further hyaluronidase was applied. Dressing changed.

4^th	72 hours post-3^rd visit	Continued lesion size reduction and healing. Profhilo^® injections are repeated. Dressing replaced.

5^th	48 hours post-4^th visit	Edema and erythema have nearly resolved. The crust adhered firmly. No Profhilo^® was applied. Dressing reapplied.

6^th	72 hours post-5^th visit	Crust detaching; significant reepithelialization observed. Profhilo^® injections are performed along lesion edges. Dressing reapplied.

7^th	7 days post-procedure	Crust fully detached. Scar tissue formed, showing a healthy appearance. Sun protection and moisturization are advised.

Profhilo^® was administered six times during different visits, resulting in the complete resolution of frontal necrosis and full re-epithelialization. (Photographs 2-5).

Photograph 2. Visit 2
Evolution after 48 hours

Photograph 3. Visit 3
Evolution after 72 hours

Photograph 4. Visit 4
Evolution after 10 days

Photograph 5. Visit 5
Results after 20 days

DISCUSSION

Managing complications from HA filler injections, particularly vascular occlusion leading to tissue necrosis, remains a critical challenge in aesthetic medicine.

Our case report highlights the importance of early identification and intervention in minimizing long-term sequelae.

The combination of meticulous debridement, targeted application of hyaluronidase, and hybrid cooperative complexes (HCC) of HA, such as Profhilo^®, proved effective in restoring tissue viability and promoting regeneration.

The standardized protocols employed, including precise microinjections and aseptic techniques, underscore the importance of clinicians adhering to evidence-based practices to achieve favorable outcomes. This approach resolved the necrotic complication and supported aesthetic recovery, emphasizing the versatility of Profhilo^® in managing both therapeutic and regenerative needs.

This case report also highlights the crucial role of education and training in reducing the risk of complications associated with HA fillers. A thorough understanding of vascular anatomy, filler rheology, and injection techniques is imperative to reduce the incidence of adverse events.

Furthermore, integrating emerging technologies, such as thermal-stabilized HA products, into clinical practice demonstrates how innovation can enhance safety and efficacy.

The use of HCC, with its dual benefits of immediate hydration and long-term collagen stimulation, offers a promising avenue for managing complex cases. Continued documentation of such cases and research into advanced treatment modalities will be essential for optimizing patient outcomes and advancing the field of aesthetic medicine

CONCLUSIONS

This protocol for managing HA vascular complications, based on the precise application of HCC, represents an advanced biomolecular intervention that combines hyaluronic acid's anti-inflammatory and regenerative effects in various forms.

The success of this protocol in treating severe complications, such as skin necrosis, lies in its ability to activate key cellular signaling pathways (MAPK/ERK and PI3K/Akt), modulate inflammation, and promote controlled and orderly tissue regeneration.

This approach provides a solid scientific justification to claim that HCC, under this protocol, is effective in reversing severe tissue damage and optimizing skin healing. Implementing the regenerative protocol resulted in the complete resolution of frontal necrosis, accompanied by full re-epithelialization by day eight. The patient experienced minimal residual scarring, achieving excellent aesthetic and clinical outcomes at day 20.

REFERENCES

1.	Funt D, Pavicic T. Dermal fillers in aesthetics: An overview of adverse events and treatment approaches. Clin Cosmet Investig Dermatol. 2013;6:295-316.
2.	Sito G, Manzoni V, Sommariva R. Vascular complications after facial filler injection: A literature review and meta-analysis. J Clin Aesthet Dermatol. 2019;12(6):E65-E72.
3.	Heydenrych I, De Boulle K, Kapoor KM, Bertossi D. The 10-point plan 2021: Updated concepts for improved procedural safety during facial filler treatments. Clin Cosmet Investig Dermatol. 2021;14:779-814. Erratum in: Clin Cosmet Investig Dermatol. 2021;14:1601-1602.
4.	Murray G, Convery C, Walker L, Davies E. Guideline for the management of hyaluronic acid filler-induced vascular occlusion. J Clin Aesthet Dermatol. 2021;14(5):E61-E69.
5.	Papakonstantinou E, Roth M, Karakiulakis G. Hyaluronic acid: A key molecule in skin aging. Dermatoendocrinol. 2012;4(3):253-8.
6.	Stellavato A, Corsuto L, D'Agostino A, La Gatta A, Diana P, Bernini P, et al. Hyaluronan hybrid cooperative complexes as a novel frontier for cellular bioprocesses re-activation. PLoS One. 2016;11(10):e0163510.
7.	Rodríguez Abascal M, Saldaña Fernández M. Bio-remodelación facial mediante inyección intradérmica de un complejo híbrido estabilizado de ácido hialurónico de alto y bajo peso molecular: estudio prospectivo en 30 pacientes. Eur Aesthetic Plast Surg J. 2015;5(2):124-131.