Введение гиалуронидазы внутриочагово для облегчения сосудистых побочных эффектов, вызванных филлерами, не содержащими гиалуроновую кислоту
Введение гиалуронидазы внутриочагово для облегчения сосудистых побочных эффектов, вызванных филлерами, не содержащими гиалуроновую кислоту.
Intralesional hyaluronidase injection to relieve non-hyaluronic acid filler-induced vascular adverse events
Jonathan Kadouch,1 Leonie Schelke,2 Olivier Groh,3 Vicky Sokol,4 and Peter Velthuis2
1ReSculpt Clinic, Practice for Aesthetic Dermatology, Amsterdam, the Netherlands,2Department of Dermatology, Erasmus Medical Centre, Rotterdam, the
Netherlands, 3Groh Kliniek, Practice for Aesthetic Medicine, Bloemendaal, the Netherlands; and 4Aesthetics by Viktorya, Practice for Aesthetic Medicine,
Lincolnshire, IL, USA
Abstract
Background
Vascular adverse events (VAEs) occurring during injections of soft-tissue fillers are still considered a challenging issue for both patients and practitioners.
Hyaluronidase can dissolve hyaluronic acid (HA)-based soft-tissue fillers during a VAE. For VAEs induced by non-HA fillers, the absence of an “antidote” is regarded as exceptionally challenging.
Methods
This multicenter study describes a case series of three VAEs induced by non-HA fillers, for which ultrasound-guided hyaluronidase injections were incorporated into the treatment approach.
Results
Two cases of calcium hydroxylapatite and one case of poly-L-lactic acid-induced VAEs are described, all of which were resolved without necrosis or scarring using a treatment approach with ultrasound-guided hyaluronidase injections.
Conclusions
Unlike the mechanical hypothesis, which assumes filler particles travel antegrade to block arterioles in a large skin area, we hypothesize vasoconstriction as the pivot in VAEs. Filler injection-induced spasms could lead to long-lasting vasoconstriction of the perforator arteries stemming from the central facial arteries. Our results underscore that perforasome vasoconstriction might be the leading cause of the ischemia and subsequent necrosis in VAEs and that relaxation of these perforasomes, rather than dissolving the filler material, resolves the clinical symptoms associated with VAEs.
Introduction
Vascular adverse events (VAEs) occurring during injections of soft-tissue fillers remain a challenging issue for both patients and practitioners. Currently accepted pathomechanisms behind VAEs following soft-tissue filler injections are based on the assumption that the injected material either causes an
intra-arterial mechanical embolus or compresses an artery.1 Hyaluronidase can dissolve hyaluronic acid (HA)-based soft-tissue fillers during a VAE or for any complications requiring filler removal.2 For non-HA fillers, the absence of an “antidote” poses additional challenges during VAEs.
In recent articles, the authors proposed an alternative hypothesis regarding the causation of VAEs.1,3 the successful treatment of patients with VAEs after HA filler injections using ultrasound-guided hyaluronidase injections. In all cases, the improvement of clinical symptoms coincided with restoring normal blood flow on Doppler ultrasound, confirming the connection between arterial blood flow and clinical symptoms.1 However, although the clinical symptoms were visible
at the skin surface, Schelke et al. describe that the HA material was identified and dissolved around a vascular blockage in the subcutaneous layers.1,3 The successful outcome of this “vascular blockage”-targeted approach suggests a role for perforator arteries stemming from the main facial arteries, also
known as the “perforasome concept” or “angiosome theory” by Taylor et al.4,5 This theory suggests that the perforator artery provides blood supply to a distinct area of soft tissue, or perforasome. Filler injection-induced spasms or the vasoconstriction of such a perforator artery might lead to ischemia and necrosis of the perforasome it supplies, leading to the clinical picture of reticulated livedoid skin changes.6
For HA filler-induced VAE, our protocol of ultrasound-guided intralesional injection of hyaluronidase immediately restored blood flow.1,3 For VAEs induced by calcium hydroxylapatite (CaHA), we used sodium thiosulphate (STS) as the primary treatment because it could dissolve CaHA.7 Additionally, we invariably used hyaluronidase, believing it might increase tissue permeability and disperse the CaHA product.1,8,9 Using this combined approach, an improvement in blood flow was observed on Doppler ultrasound imaging in all patients.
Given the doubts about the effectiveness of STS in dissolving CaHA and the revisited model of arterial blood flow being affected by soft-tissue filler injections,1,3,10 we decided to use hyaluronidase as the primary treatment in CaHA (and other non-HA) VAE cases, keeping STS in reserve. In this article, we
describe three cases of VAEs induced by non-HA fillers and successfully treated with ultrasound-guided hyaluronidase injections using the protocol described by Schelke et al.2
Patient 1
A patient was referred to our Filler Complication Clinic (Dermatology Department of the Erasmus Medical Centre, Amsterdam, the Netherlands) with a VAE after a bolus injection (0.2 ml) of CaHA with a needle on the caudal part of the chin 3 days earlier. During the presentation, a reticulated livedoid skin pattern
was visible on the left side of her chin, reaching cranially toward the lower lip and caudally into the neck (Figure 1). A hematoma was also present. The patient had pain at the level of the liveoid skin pattern but also along the left jawline, possibly because of the extensive swelling.
Figure 1 Caudal part of the chin, presumably the flow area of a
perforasome stemming from the submental artery. Clinically
triangular shape with a broad basis and a point reaching cranially
and caudally to the neck. Hematoma present
On duplex ultrasound imaging, some hypervascular arterial blood flow of the left submental artery was visible. The subcutaneous tissue underneath the livedo skin pattern showed an absence of flow. CaHA filler was visible as a well-defined hyperechoic deposit with posterior acoustic shadowing.11 Under duplex ultrasound guidance, we injected 150 units of hyaluronidase (Hyason, Organon, the Netherlands) at the level of SMAS, where the flow was diminished. After minutes, restoration of blood flow of the perforator and smaller arterioles in the subcutaneous layer was observed (Video S1). As observed with duplex ultrasound examination, all vascular adverse events with CaHA show more inflammation than HA, so prednisolone 20 mg and acetylsalicylic acid 500 mg daily were given orally for 5 days. The patient healed without scarring.
Patient 2
A 53-year-old female patient underwent a second treatment of hyperdiluted CaHA of the face. The CaHA was reconstituted at 1:2 with 0.5 ml of 2% lidocaine and 2.5 ml of bacteriostatic saline, after which the treatment was performed with a 22G 70mm cannula. The entry points were anesthetized locally with
0.15 ml of 1% lidocaine with epinephrine per point. After injecting approximately 2 ml of the hyperdiluted CaHA, the aesthetic practitioner noticed some bruising starting to occur on the patient’s right lower face. The patient applied pressure on the affected area while the contralateral side was also treated with 2.5 ml of
the hyperdiluted mixture. After this, the patient began to feel lightheaded and dizzy when turning the head from side to side. The patient had mild swelling and a good capillary refill. Ice packs were given to the patient to apply to the swelling and bruising of the lower right side of the face. Neurological assessment
(pupils, eyes, etc.) performed the same day was normal.
The patient was reevaluated the following day. At physical examination, bruising/hematoma, swelling, and a marbling skin pattern were visible under the right zygomatic arch. The patient underwent an MRI with and without contrast, with no abnormalities. The CaHA filler was visible on duplex ultrasound imaging
as a well-defined hyperechoic deposit with posterior acoustic shadowing. The subcutaneous tissue close to the CaHA deposits and underneath the livedo skin pattern showed an absence of flow. Surrounding the filler material, some hypervascular arterial blood flow of the right transverse facial artery and
corresponding microvascularisation were observed. Under duplex ultrasound guidance, 300 units of hyaluronidase were injected at the level of SMAS, where the flow was diminished, after which the capillary refill improved. Under Doppler ultrasound, the blood flow of the perforator and smaller arterioles in the affected area also showed improvement. The patient was started on a high prednisone dose and meclizine.
On Day 3, the patient, who started to feel better with slowly diminishing vertigo complaints, was reevaluated. The bruising and swelling had subsided as well. The blood flow to the affected area was still improved on duplex ultrasound imaging. An additional 150 units of hyaluronidase were injected under
ultrasound guidance to diminish the hematoma and swelling. In the following days, the patient steadily improved; by Day 11, all symptoms of bruising/livedo skin pattern and vertigo had dissipated entirely. The patient healed without scarring.
Patient 3
A 52-year-old female patient underwent treatment of the face with a biostimulatory filler (Lanluma, polylactic acid, PLLA, GCS Co. Ltd, Gyeonggi-do, Korea). The PLLA was reconstituted with 20 ml of sterile water and 2.0 ml of 1% lidocaine, after which the treatment was performed with a 22G 50 mm cannula. The entry points were anesthetized locally with 1% lidocaine with epinephrine per point. First, the temples were treated with 1.5 ml per side. After the injection of the right side of the zygomatic area, blanching and discoloration of the skin of the treated area were noted. The capillary refill was delayed.
A duplex ultrasound examination of the affected area was performed. The injected PLLA was visible as an ill-defined hypoechoic band with some posterior shadowing. Surrounding the filler product, hypervascular arterial blood flow of the right transverse facial artery was observed. A total of 500 units of
hyaluronidase were injected at the level of the SMAS, where aberrant blood flow and disturbed microvascularisation were observed. Within minutes, a restoration of normal blood flow of the transverse facial artery and the perforator into the superficial fatty layer was observed. The patient was started on acetylsalicylic acid 300 mg daily in combination with pantoprazole 40 mg daily for a week. The patient healed without scarring.
Discussion
Up until now, it was generally assumed that an embolus composed of the involved filler substance is the most likely cause of hypoxia, leading to a focus on treatment strategies that dissolve the material. Indeed, when applying hyaluronidase injections for HA-induced VAEs, this approach worked well and seemed to
support the idea that we were dissolving the HA filler embolus.1,3 However, when we analyze the currently available literature on this topic, no study has yet been able to demonstrate or prove in vivo that filler-injection-induced tissue necrosis is the result of intravascular injection of filler material leading to a filler embolus that mechanically obstructs blood flow and causes ischemia. Furthermore, no study has proven that in VAE cases, the hyaluronidase is precisely injected into the affected blood vessel or ends up inside the bloodstream through passive diffusion and truly dissolves a filler embolus. Delivery of hyaluronidase exactly at the location of the HA embolus would be crucial for success.
Recently, the perforasome concept, derived from the angiosome theory by Taylor et al.,4,5 has been introduced. This concept suggests that one artery, the perforator, provides blood supply to a distinct soft tissue area (the perforasome). This perforasome depends on the blood supply of that specific vessel for survival,6,12 although neighboring perforators are connected by anastomoses. If the hypothesis that the filler-induced spasm of the perforator arteries and the connecting anastomoses are the leading cause of VAE after filler injection is correct, VAE treatment must be aimed at releasing this spasm. Interestingly,
hyaluronidase has been proven to have properties that restore vasospasms in mice.13
Because reports cast doubt on the effect of STS in dissolving CaHA and we noted initial success with the combined STS/hyaluronidase treatment, we used hyaluronidase as a single treatment approach in these two cases of CaHA-induced VAE. The efficacy of this approach in CaHA-induced VAE, as well as in the case of PLLA-induced VAE, sheds new light on the pathophysiology and treatment of VAEs after filler injection. One could argue that in cases of HA-induced VAE, effective treatment with hyaluronidase is not because an HA filler embolus is dissolved but because a direct action of the enzyme releases the vasospasm. Considering these publications and the growing support for the vasospasm hypothesis,1,3,6 the idea that we are truly dissolving a focus of intra-arterial filler embolus should at least be questioned and critically investigated. Furthermore, several publications have described the clinical perforasome-based livedo patterns of the skin associated with VAEs.2,6 If an intra-arterial lodged filler embolus were the leading cause of VAEs, one would expect to see more irregular skin patterns and necrosis instead of the currently described recurrent perforasome-based distributions. The hypothesis that hyaluronidase can relax perforasome vasospasms could also explain past successes with this treatment approach.13 More research is necessary to elucidate the exact pathophysiological mechanism that leads to filler-injectioninduced ischemia and necrosis.
Conclusion
The generally accepted theory behind filler-injection-induced VAEs is that intravascular injection of filler material leads to a filler embolus blocking blood flow and leading to tissue ischemia and necrosis. The introduction of handheld ultrasound devices used for ultrasound-guided hyaluronidase injections in VAE
cases and recent insights into the anatomical organization of angiosomes and perforasomes have opened the door to alternative hypotheses and a possible role for vasospams as a cause for ischemia and necrosis in filler VAEs. This shows that more research is necessary to assess the exact pathophysiology
of this important complication.
Declarations
All treatments were performed in accordance with the Declaration of Helsinki and the standards of good clinical care, following local guidelines and regulations. This article does not contain any studies with animals performed by any of the authors.
Patient consent
All patients included in this study provided written informed consent to access their charts and extract their data for this study. No charts were accessed if patients declined participation in this study.
Intralesional hyaluronidase injection to relieve non-hyaluronic acid filler-induced vascular adverse events
Jonathan Kadouch,1 Leonie Schelke,2 Olivier Groh,3 Vicky Sokol,4 and Peter Velthuis2
1ReSculpt Clinic, Practice for Aesthetic Dermatology, Amsterdam, the Netherlands,2Department of Dermatology, Erasmus Medical Centre, Rotterdam, the
Netherlands, 3Groh Kliniek, Practice for Aesthetic Medicine, Bloemendaal, the Netherlands; and 4Aesthetics by Viktorya, Practice for Aesthetic Medicine,
Lincolnshire, IL, USA
Abstract
Background
Vascular adverse events (VAEs) occurring during injections of soft-tissue fillers are still considered a challenging issue for both patients and practitioners.
Hyaluronidase can dissolve hyaluronic acid (HA)-based soft-tissue fillers during a VAE. For VAEs induced by non-HA fillers, the absence of an “antidote” is regarded as exceptionally challenging.
Methods
This multicenter study describes a case series of three VAEs induced by non-HA fillers, for which ultrasound-guided hyaluronidase injections were incorporated into the treatment approach.
Results
Two cases of calcium hydroxylapatite and one case of poly-L-lactic acid-induced VAEs are described, all of which were resolved without necrosis or scarring using a treatment approach with ultrasound-guided hyaluronidase injections.
Conclusions
Unlike the mechanical hypothesis, which assumes filler particles travel antegrade to block arterioles in a large skin area, we hypothesize vasoconstriction as the pivot in VAEs. Filler injection-induced spasms could lead to long-lasting vasoconstriction of the perforator arteries stemming from the central facial arteries. Our results underscore that perforasome vasoconstriction might be the leading cause of the ischemia and subsequent necrosis in VAEs and that relaxation of these perforasomes, rather than dissolving the filler material, resolves the clinical symptoms associated with VAEs.
Introduction
Vascular adverse events (VAEs) occurring during injections of soft-tissue fillers remain a challenging issue for both patients and practitioners. Currently accepted pathomechanisms behind VAEs following soft-tissue filler injections are based on the assumption that the injected material either causes an
intra-arterial mechanical embolus or compresses an artery.1 Hyaluronidase can dissolve hyaluronic acid (HA)-based soft-tissue fillers during a VAE or for any complications requiring filler removal.2 For non-HA fillers, the absence of an “antidote” poses additional challenges during VAEs.
In recent articles, the authors proposed an alternative hypothesis regarding the causation of VAEs.1,3 the successful treatment of patients with VAEs after HA filler injections using ultrasound-guided hyaluronidase injections. In all cases, the improvement of clinical symptoms coincided with restoring normal blood flow on Doppler ultrasound, confirming the connection between arterial blood flow and clinical symptoms.1 However, although the clinical symptoms were visible
at the skin surface, Schelke et al. describe that the HA material was identified and dissolved around a vascular blockage in the subcutaneous layers.1,3 The successful outcome of this “vascular blockage”-targeted approach suggests a role for perforator arteries stemming from the main facial arteries, also
known as the “perforasome concept” or “angiosome theory” by Taylor et al.4,5 This theory suggests that the perforator artery provides blood supply to a distinct area of soft tissue, or perforasome. Filler injection-induced spasms or the vasoconstriction of such a perforator artery might lead to ischemia and necrosis of the perforasome it supplies, leading to the clinical picture of reticulated livedoid skin changes.6
For HA filler-induced VAE, our protocol of ultrasound-guided intralesional injection of hyaluronidase immediately restored blood flow.1,3 For VAEs induced by calcium hydroxylapatite (CaHA), we used sodium thiosulphate (STS) as the primary treatment because it could dissolve CaHA.7 Additionally, we invariably used hyaluronidase, believing it might increase tissue permeability and disperse the CaHA product.1,8,9 Using this combined approach, an improvement in blood flow was observed on Doppler ultrasound imaging in all patients.
Given the doubts about the effectiveness of STS in dissolving CaHA and the revisited model of arterial blood flow being affected by soft-tissue filler injections,1,3,10 we decided to use hyaluronidase as the primary treatment in CaHA (and other non-HA) VAE cases, keeping STS in reserve. In this article, we
describe three cases of VAEs induced by non-HA fillers and successfully treated with ultrasound-guided hyaluronidase injections using the protocol described by Schelke et al.2
Patient 1
A patient was referred to our Filler Complication Clinic (Dermatology Department of the Erasmus Medical Centre, Amsterdam, the Netherlands) with a VAE after a bolus injection (0.2 ml) of CaHA with a needle on the caudal part of the chin 3 days earlier. During the presentation, a reticulated livedoid skin pattern
was visible on the left side of her chin, reaching cranially toward the lower lip and caudally into the neck (Figure 1). A hematoma was also present. The patient had pain at the level of the liveoid skin pattern but also along the left jawline, possibly because of the extensive swelling.
Figure 1 Caudal part of the chin, presumably the flow area of a
perforasome stemming from the submental artery. Clinically
triangular shape with a broad basis and a point reaching cranially
and caudally to the neck. Hematoma present
On duplex ultrasound imaging, some hypervascular arterial blood flow of the left submental artery was visible. The subcutaneous tissue underneath the livedo skin pattern showed an absence of flow. CaHA filler was visible as a well-defined hyperechoic deposit with posterior acoustic shadowing.11 Under duplex ultrasound guidance, we injected 150 units of hyaluronidase (Hyason, Organon, the Netherlands) at the level of SMAS, where the flow was diminished. After minutes, restoration of blood flow of the perforator and smaller arterioles in the subcutaneous layer was observed (Video S1). As observed with duplex ultrasound examination, all vascular adverse events with CaHA show more inflammation than HA, so prednisolone 20 mg and acetylsalicylic acid 500 mg daily were given orally for 5 days. The patient healed without scarring.
Patient 2
A 53-year-old female patient underwent a second treatment of hyperdiluted CaHA of the face. The CaHA was reconstituted at 1:2 with 0.5 ml of 2% lidocaine and 2.5 ml of bacteriostatic saline, after which the treatment was performed with a 22G 70mm cannula. The entry points were anesthetized locally with
0.15 ml of 1% lidocaine with epinephrine per point. After injecting approximately 2 ml of the hyperdiluted CaHA, the aesthetic practitioner noticed some bruising starting to occur on the patient’s right lower face. The patient applied pressure on the affected area while the contralateral side was also treated with 2.5 ml of
the hyperdiluted mixture. After this, the patient began to feel lightheaded and dizzy when turning the head from side to side. The patient had mild swelling and a good capillary refill. Ice packs were given to the patient to apply to the swelling and bruising of the lower right side of the face. Neurological assessment
(pupils, eyes, etc.) performed the same day was normal.
The patient was reevaluated the following day. At physical examination, bruising/hematoma, swelling, and a marbling skin pattern were visible under the right zygomatic arch. The patient underwent an MRI with and without contrast, with no abnormalities. The CaHA filler was visible on duplex ultrasound imaging
as a well-defined hyperechoic deposit with posterior acoustic shadowing. The subcutaneous tissue close to the CaHA deposits and underneath the livedo skin pattern showed an absence of flow. Surrounding the filler material, some hypervascular arterial blood flow of the right transverse facial artery and
corresponding microvascularisation were observed. Under duplex ultrasound guidance, 300 units of hyaluronidase were injected at the level of SMAS, where the flow was diminished, after which the capillary refill improved. Under Doppler ultrasound, the blood flow of the perforator and smaller arterioles in the affected area also showed improvement. The patient was started on a high prednisone dose and meclizine.
On Day 3, the patient, who started to feel better with slowly diminishing vertigo complaints, was reevaluated. The bruising and swelling had subsided as well. The blood flow to the affected area was still improved on duplex ultrasound imaging. An additional 150 units of hyaluronidase were injected under
ultrasound guidance to diminish the hematoma and swelling. In the following days, the patient steadily improved; by Day 11, all symptoms of bruising/livedo skin pattern and vertigo had dissipated entirely. The patient healed without scarring.
Patient 3
A 52-year-old female patient underwent treatment of the face with a biostimulatory filler (Lanluma, polylactic acid, PLLA, GCS Co. Ltd, Gyeonggi-do, Korea). The PLLA was reconstituted with 20 ml of sterile water and 2.0 ml of 1% lidocaine, after which the treatment was performed with a 22G 50 mm cannula. The entry points were anesthetized locally with 1% lidocaine with epinephrine per point. First, the temples were treated with 1.5 ml per side. After the injection of the right side of the zygomatic area, blanching and discoloration of the skin of the treated area were noted. The capillary refill was delayed.
A duplex ultrasound examination of the affected area was performed. The injected PLLA was visible as an ill-defined hypoechoic band with some posterior shadowing. Surrounding the filler product, hypervascular arterial blood flow of the right transverse facial artery was observed. A total of 500 units of
hyaluronidase were injected at the level of the SMAS, where aberrant blood flow and disturbed microvascularisation were observed. Within minutes, a restoration of normal blood flow of the transverse facial artery and the perforator into the superficial fatty layer was observed. The patient was started on acetylsalicylic acid 300 mg daily in combination with pantoprazole 40 mg daily for a week. The patient healed without scarring.
Discussion
Up until now, it was generally assumed that an embolus composed of the involved filler substance is the most likely cause of hypoxia, leading to a focus on treatment strategies that dissolve the material. Indeed, when applying hyaluronidase injections for HA-induced VAEs, this approach worked well and seemed to
support the idea that we were dissolving the HA filler embolus.1,3 However, when we analyze the currently available literature on this topic, no study has yet been able to demonstrate or prove in vivo that filler-injection-induced tissue necrosis is the result of intravascular injection of filler material leading to a filler embolus that mechanically obstructs blood flow and causes ischemia. Furthermore, no study has proven that in VAE cases, the hyaluronidase is precisely injected into the affected blood vessel or ends up inside the bloodstream through passive diffusion and truly dissolves a filler embolus. Delivery of hyaluronidase exactly at the location of the HA embolus would be crucial for success.
Recently, the perforasome concept, derived from the angiosome theory by Taylor et al.,4,5 has been introduced. This concept suggests that one artery, the perforator, provides blood supply to a distinct soft tissue area (the perforasome). This perforasome depends on the blood supply of that specific vessel for survival,6,12 although neighboring perforators are connected by anastomoses. If the hypothesis that the filler-induced spasm of the perforator arteries and the connecting anastomoses are the leading cause of VAE after filler injection is correct, VAE treatment must be aimed at releasing this spasm. Interestingly,
hyaluronidase has been proven to have properties that restore vasospasms in mice.13
Because reports cast doubt on the effect of STS in dissolving CaHA and we noted initial success with the combined STS/hyaluronidase treatment, we used hyaluronidase as a single treatment approach in these two cases of CaHA-induced VAE. The efficacy of this approach in CaHA-induced VAE, as well as in the case of PLLA-induced VAE, sheds new light on the pathophysiology and treatment of VAEs after filler injection. One could argue that in cases of HA-induced VAE, effective treatment with hyaluronidase is not because an HA filler embolus is dissolved but because a direct action of the enzyme releases the vasospasm. Considering these publications and the growing support for the vasospasm hypothesis,1,3,6 the idea that we are truly dissolving a focus of intra-arterial filler embolus should at least be questioned and critically investigated. Furthermore, several publications have described the clinical perforasome-based livedo patterns of the skin associated with VAEs.2,6 If an intra-arterial lodged filler embolus were the leading cause of VAEs, one would expect to see more irregular skin patterns and necrosis instead of the currently described recurrent perforasome-based distributions. The hypothesis that hyaluronidase can relax perforasome vasospasms could also explain past successes with this treatment approach.13 More research is necessary to elucidate the exact pathophysiological mechanism that leads to filler-injectioninduced ischemia and necrosis.
Conclusion
The generally accepted theory behind filler-injection-induced VAEs is that intravascular injection of filler material leads to a filler embolus blocking blood flow and leading to tissue ischemia and necrosis. The introduction of handheld ultrasound devices used for ultrasound-guided hyaluronidase injections in VAE
cases and recent insights into the anatomical organization of angiosomes and perforasomes have opened the door to alternative hypotheses and a possible role for vasospams as a cause for ischemia and necrosis in filler VAEs. This shows that more research is necessary to assess the exact pathophysiology
of this important complication.
Declarations
All treatments were performed in accordance with the Declaration of Helsinki and the standards of good clinical care, following local guidelines and regulations. This article does not contain any studies with animals performed by any of the authors.
Patient consent
All patients included in this study provided written informed consent to access their charts and extract their data for this study. No charts were accessed if patients declined participation in this study.