Intralesional hyaluronidase injection to relieve non-hyaluronic acid filler-induced vascular adverse events.

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.

Jawline Sharp Contouring With Hybrid Filler.

BACKGROUND: Having a well-defined jawline is a sign of youth and attractiveness among both men and women. Soft tissue fillers, such as calcium hydroxylapatite (CaHA) and hyaluronic acid (HA) fillers, offer nonsurgical alternatives for rejuvenating the lower face and enhancing the jawline. The aim of this study was to investigate the use of a premixed combination of HA with cohesive polydensified matrix technology (CPM, Belotero Intense, CPM-I) and CaHA to create a sharply defined jawline. METHODS: A total of 126 patients were enrolled in the study and treated with a premixed combination of CPM-I and CaHA using a retrograde fanning injection technique with cannulas. The injection volumes and product ratios were customized according to the patients' needs. RESULTS: The cohort consisted of 75 females and 51 males. The average injected volume of premixed CaHA:CPM-I was 5.83 mL. In the majority of patients, a 1:1 syringe ratio of CaHA:CPM-I was applied (n = 81, 64.2%). No adverse events were reported during the 6-month follow-up period. CONCLUSION: The hybrid filler approach investigated in this study shows promise for achieving well-defined, long-lasting jawline contours. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors   www.springer.com/00266 .

Hand Rejuvenation with Customizable Hybrid Fillers: Premixed Calcium Hydroxyapatite and Hyaluronic Acid.

INTRODUCTION: Hand aging is a prevalent concern characterized by the atrophy of local soft tissues and increased visibility of vessels and tendons. Hyaluronic acid (HA) and calcium hydroxyapatite (CaHA) are well-established treatments for addressing this issue. While hybrid filler containing HA and CaHA has been proposed for facial rejuvenation, studies investigating its efficacy for hand rejuvenation are lacking. OBJECTIVE: This study aims to assess the safety and efficacy of a premixed hybrid filler containing calcium hydroxyapatite (CaHA) and hyaluronic acid (HA) for hand rejuvenation. METHODS: A prospective, double-blind, controlled trial was conducted. The control arm (CA) received conventional subdermal treatment with CaHA at a 1:1 dilution. The intervention arm (IA) underwent hybrid treatment, consisting of CaHA at a 1:1 dilution combined with 1 ml of low-density HA. Evaluation was performed subjectively using the Global Aesthetic Improvement Scale (GAIS) and the Manchester Hand Grading System (MHGS), and objectively using cutometry, corneometry, and ultrasound. RESULTS: Both the CA and the IA exhibited high rates of patient satisfaction and satisfaction as assessed by blinded evaluators. Although numerical superiority was observed in the IA, no statistical difference was found between the two groups. Significant improvements in hydration, elasticity, and skin thickness were observed in both arms, with no discernible difference between them. Greater ultrasound echogenicity was noted in the IA, which, as indicated by existing literature, may suggest enhanced biostimulation. No adverse effects were reported in either arm. CONCLUSION: Premixed filler containing HA and CaHA for hand rejuvenation appears to be a safe and effective approach. LEVEL OF EVIDENCE I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Role of Hyperbaric Oxygen in Filler-Induced Vascular Occlusion.

INTRODUCTION: The rising incidence of filler-induced vascular complications in the context of aesthetic procedures necessitates a thorough assessment of therapeutic options. Hyperbaric oxygen therapy (HBOT) has emerged as a potential intervention for filler-induced vascular occlusion (FIVO), although optimal dosing and timing remain undefined. METHODS: This review explores the pathophysiology of FIVO and elucidates HBOT's multifaceted role in salvaging ischemic tissue. The physical and biochemical mechanisms of HBOT, including its vasodilatory, anti-spasmodic, and anti-inflammatory effects, are examined. RESULTS: HBOT serves as an adjunctive therapy in FIVO management, emphasizing timely intervention, adherence to specific pressures (two atmosphere absolute), and session durations (60 minutes) to optimize efficacy and minimize complications. While existing HBOT protocols for compromised grafts provide insights, standardized guidelines for FIVO are lacking. CONCLUSION: HBOT enhances tissue oxygenation, modulates reactive oxygen species, and influences angiogenesis and hypoxia response. However, it does not replace key treatment protocols for filler vascular complications. Further research and standardized protocols are warranted to define HBOT's definitive role in mitigating filler-induced vascular complications. Level of Evidence IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Updated Filler Emergency Kit: Next-Generation Emergency Solution.

INTRODUCTION: The rising popularity of facial filler injections has corresponded with an increase in reported complications. While a filler emergency kit was previously introduced, advancements in the field have highlighted certain limitations, prompting the development of the updated filler emergency kit (UFEK). METHODS: The authors conducted literature research up to February 2023, focusing on PubMed and open web searches for articles referred to filler emergent complications: vascular occlusion, blindness and anaphylaxis. Approximately 1200 articles were obtained from PubMed and other sources, and 45 articles were reviewed. RESULTS: The developed UFEK protocol delineates specific interventions meticulously tailored to address diverse emergent scenarios linked to soft tissue fillers complications. This protocol emphasizes the urgent requirement for timely and personalized interventions. CONCLUSION: The UFEK offers a standardized, comprehensive and effective approach. This work contributes to the responsible and informed progression of the field of aesthetic medicine, providing more value and safety, both for clinicians and patients. Level of Evidence IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Early ultrasound for diagnosis and treatment of vascular adverse events with hyaluronic acid fillers.

BACKGROUND: Hyaluronic acid fillers are known for a reliable safety profile, but complications do occur, even serious vascular adverse events. OBJECTIVE: To improve the treatment outcome after a vascular adverse event with use of hyaluronic acid filler treatments. METHODS: Duplex ultrasonography is used to detect the hyaluronic acid filler causing the intra-arterial obstruction. RESULTS: If treated in time, 1 single treatment of ultrasonographically guided injections of hyaluronidase into the filler deposit will prevent skin necrosis. CONCLUSION: Because the use of duplex ultrasonography adds extra essential information, its use may become an integral part of the prevention and treatment of injection adverse events.

Ultrasound-Guided Targeted vs Regional Flooding: A Comparative Study for Improving the Clinical Outcome in Soft Tissue Filler Vascular Adverse Event Management.

BACKGROUND: Adverse vascular event management following hyaluronic acid-based aesthetic injections relies on the administration of hyaluronidase which is capable of enzymatically degrading the injected product and improving clinical symptoms. Two protocols are currently available to manage such complications: "ultrasound-guided targeted" and "flooding". OBJECTIVES: The aim of this study was to compare the 2 protocols in terms of the volume of hyaluronidase utilized, and the onset and degree of clinical improvement. METHODS: A comparative case series of 39 patients was retrospectively evaluated. The patients were initially treated with the "flooding" protocol and then treated with the "ultrasound-guided targeted" protocol due to no or little improvement. RESULTS: The "ultrasound-guided targeted" protocol utilized a mean [standard deviation] total of 122.5 [34] IU of hyaluronidase, whereas the "flooding" protocol utilized 1519.4 [1137] IU, which represents a statistically significant reduced amount of injected hyaluronidase (P = 0.028). There was no clinical improvement in 92.3% and only little improvement in 7.7% of the treated patients following the first applied "flooding" protocol, but there was a 100% immediate improvement when subsequently treated with the "ultrasound-guided targeted" protocol. Ultrasound imaging revealed that the application of hyaluronidase restored normal blood flow both in the perivascular space and in the superficially located subdermal soft tissues. CONCLUSIONS: Despite its limitations in study design, this retrospectively evaluated case series revealed that the "ultrasound-guided targeted" protocol utilized less hyaluronidase and restored clinically visible symptoms faster. The effect of this protocol is best explained by the perforasome concept which will need to be investigated further in future studies.

Late inflammatory reactions in patients with soft tissue fillers after SARS-CoV-2 infection and vaccination: A systematic review of the literature.

INTRODUCTION: Soft tissue fillers are used for cosmetic and reconstructive purposes, and soft tissue filler procedures are among the most common nonsurgical procedures in the USA. Although soft tissue filler procedures are relatively quick and safe, adverse events such as late inflammatory reactions have been reported with every filler product. Infections and vaccinations have been proposed as potential triggers for late inflammatory reactions (LIRs), and it is therefore not surprising that these adverse events have been reported after SARS-CoV-2 infection and vaccination. Therefore, this review aims to give a detailed overview of these cases. MATERIALS AND METHODS: A literature search was undertaken on LIRs in patients with a history of soft tissue filler use after SARS-CoV-2 infection or vaccination. This systematic review was reported according to the PRISMA guidelines. We searched the electronic database PubMed from January 2020 to August 2021. Data on patient characteristics, filler characteristics, clinical findings, and treatment options were included. RESULTS: This review included 7 articles with a total of 19 patients with LIRs after SARS-CoV-2 infection or vaccination. Three patients with postinfection LIRs and 16 patients with postvaccination LIRs were reported. These LIRS mainly occurred in females who had HA injections for cosmetic purposes. Three patients with postinfection LIRs had symptoms of facial swelling and/or lip angioedema in a matter of weeks. Sixteen patients reported reactions after SARS-CoV-2 vaccination (13 following Moderna vaccination and 3 after Pfizer vaccination, after both the first and second doses) from 13 hours up to three weeks. These patients presented with similar clinical symptoms as patients with postinfection LIRs. All patients were treated in a conservative manner. DISCUSSION: This review shows a relationship between LIRs and SARS-CoV-2 infection and vaccination. In the case of vaccination, these adverse events have been reported only after Moderna and Pfizer vaccinations. The reported adverse events are generally minor and self-limiting, and we encourage patients with soft tissue fillers to participate in vaccination programs.

Combining Calcium Hydroxylapatite and Hyaluronic Acid Fillers for Aesthetic Indications: Efficacy of an Innovative Hybrid Filler.

BACKGROUND: Limited data are available describing effectiveness of combining the use of calcium hydroxylapatite (CaHA) and hyaluronic acid (HA). METHODS: The authors performed a retrospective chart review of patients injected with a premixed combination of CaHA and a cohesive polydensified matrix (CPM®) HA (CaHA:CPM-HA ) in the authors' aesthetic practices. The midface and lower face were injected. Patients' records were evaluated, and treatment results were scored using the Merz Aesthetics Scale for the jawline® (clinician rated, CR-MASJ). Adverse events were recorded. RESULTS: A total of 41 patients were included, all females with a mean age of 47.5 years (range 21-63 years). The mean CR-MASJ score improved from 2.12 at baseline to 0.68 at t = 3 months (SD = 0.69, 95% CI 1.28-1.60) and 1.27 at t = 12 months (SD = 0.74, 95% CI 0.43-0.74). 100% of the subjects had experienced a ≥1-point improvement in CR-MASJ score at t = 3 months, versus 85% at t = 12 months. No adverse events were reported. CONCLUSION: The results of this study support the volumizing and lifting potential of the hybrid mix CaHA:CPM-HA for treatment of cheeks and jawline. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Immediate nor Delayed Type Hypersensitivity Plays a Role in Late Inflammatory Reactions After Hyaluronic Acid Filler Injections.

PURPOSE: The exact etiology of late inflammatory reactions (LIRs) to hyaluronic acid (HA) fillers is currently unknown. Some argue that these result from a hypersensitivity reaction, although evidence to support this is very scarce. Most reports on such reactions are not substantiated by positive skin tests. The purpose of our study was to determine whether immediate or delayed type hypersensitivity reaction follows hyaluronic acid (HA) filler injections. PATIENTS AND METHODS: Twelve patients were referred for general allergic screening (patch tests), as well as specific intradermal testing (injection of 0.1cc boluses) on the medial upper arm with a selection of several currently available hyaluronic acid (HA) fillers on the market. A positive allergic reaction was defined as erythema, firmness or swelling. RESULTS: During the 4 month follow-up, no reactions to any of the tested HA fillers were reported. No correlation was found between results from the general allergic screening and a history with LIRs to HA fillers. CONCLUSION: The results suggest that neither type I nor type IV hypersensitivity plays a role in late inflammatory reactions (LIRs) to hyaluronic acid (HA) fillers.

A Guide to Doppler Ultrasound Analysis of the Face in Cosmetic Medicine. Part 1: Standard Positions.

Interest in Doppler ultrasound (DUS) analysis of the face has grown in cosmetic medicine, in particular for injectable fillers. When dealing with complications, DUS has the advantage of easily visualizing the filler and identifying the problem in relation to the patient's anatomy. When working with hyaluronic acid filler, ultrasound-guided injections with hyaluronidase can precisely target the problem. In addition, DUS can be used to study the anatomy of a patient, specifically to prevent intravascular injections. We predict that in a few years' time DUS will become standard equipment in the offices of cosmetic doctors. We discuss the basics of ultrasound imaging of different tissues with the concomitant terminology. With the use of 7 basic DUS probe positions, key anatomic reference points can be easily found. From these, all relevant anatomic structures in the face can be observed and analyzed. With some practice, physicians will ultimately be able to acquire a complete 3-dimensional mental image of a patient's face.

A Guide to Doppler Ultrasound Analysis of the Face in Cosmetic Medicine. Part 2: Vascular Mapping.

Duplex mode ultrasound imaging can detect the course of the main vascular structures in the face, which are known to be subject to variation. Once duplex mapping has been performed, measures can be taken to prevent injection into an artery, thereby avoiding skin necrosis or, worse, vision loss. For this reason, in particular, we predict that in the coming years sonography will become standard equipment in the offices of cosmetic doctors. We discuss the basics of vascular imaging by Doppler ultrasound, both in normal and pathologic situations. Starting from the 7 basic positions for the ultrasound probe, all facial arteries relevant in cosmetic medicine can be found.

Ultrasound to Improve the Safety and Efficacy of Lipofilling of the Temples.

BACKGROUND: Autologous fat is known for a reliable and natural safety profile, but complications do occur-even serious vascular adverse events. OBJECTIVES: The authors sought to examine doppler-ultrasound (DUS) imaging for the harvesting and subsequent facial implantation of autologous fat tissue. METHODS: All patients underwent lipofilling treatment of the temporal fosse of the face. DUS examination was performed for preprocedural vascular mapping and imaging of previously injected (permanent) fillers. In addition, the injection of autologous fat was performed DUS-guided. RESULTS: Twenty patients (all female; mean age, 57.9 years; range, 35-64 years). DUS examination showed that 16 of the 20 patients (80%) had been injected with resorbable or nonresorbable fillers elsewhere in the past. The temporal artery could be visualized and avoided in all cases. An average of 1.1 cc of autologous fat was injected in the temporal fossa per side. One case of edema and nodules was described, but no other adverse events were reported. CONCLUSIONS: The utilization of DUS can add valuable information to a lipofilling procedure and should be considered an integral part of a safe lipofilling treatment.

Managing intravascular complications following treatment with calcium hydroxylapatite: An expert consensus.

BACKGROUND: Inadvertent intra-arterial injection of dermal fillers including calcium hydroxylapatite (CaHA) can result in serious adverse events including soft tissue necrosis, permanent scarring, visual impairment, and blindness. When intra-arterial injection occurs, immediate action is required for optimal outcomes, but the infrequency of this event means that many physicians may never have experienced this scenario. The aim of this document is to provide evidence-based and expert opinion recommendations for the recognition and management of vascular compromise following inadvertent injection of CaHA. METHODS: An international group of experts with experience in injection of CaHA and management of vascular complications was convened to develop a consensus on the optimal management of vascular compromise following intra-arterial CaHA injection. The consensus members were asked to provide preventative advice for the avoidance of intravascular injection and to produce a treatment protocol for acute and delayed presentation. To ensure all relevant treatment options were included, the recommendations were supplemented with a PubMed search of the literature. RESULTS: For prevention of intra-arterial CaHA injection, consensus members outlined the importance of a thorough knowledge of facial vascular anatomy and patient history, as well as highlighting potential risk zones and optimal injection techniques. Individual sections document how to recognize the symptoms of vascular occlusion leading to vision loss and tissue necrosis as well as detailed treatment protocols for the management of these events. For impending tissue necrosis, recommendations are provided for early and delayed presentations with treatment protocols for acute and follow-up treatment. A separate section details the treatment options for open and closed wounds. CONCLUSIONS: All physicians should be prepared for the eventuality of intra-arterial injection of a dermal filler, despite its rarity. These consensus recommendations combine advice from aesthetic experts with the latest reports from the published literature to provide an up-to-date office-based protocol for the prevention and treatment of complications arising from intra-arterial CaHA injection.

Granulomatous foreign-body reactions to permanent fillers: detection of CD123+ plasmacytoid dendritic cells.

BACKGROUND: Soft-tissue augmentation with permanent fillers can lead to severe granulomatous foreign-body reactions (GFBRs), but the immune pathomechanism of this complication is still unknown. We performed conventional histologic examination and immunostaining for plasmacytoid dendritic cells (pDCs) in skin sections from patients with GFBR to 4 permanent filler agents, which have been widely used in recent decades. METHODS: Twenty-one skin biopsies were studied from 19 patients with GFBR to polyalkylimide 4% gel (PAIG, n = 10), polyacrylamide 2.5% gel (PAAG, n = 2), hydroxyethyl methacrylate/ethyl methacrylate in hyaluronic acid (HEMA/EMA, n = 4), or liquid injectable silicone (n = 5). GFBRs were analyzed in hematoxylin and eosin stained sections and pDCs detected using CD123 antibodies. Anti-CD11c immunostaining was performed for comparison. RESULTS: Grading of the inflammatory infiltrates observed histologically did not correlate with the clinical features of inflammation. Immunostaining for CD123 did not detect pDCs in 8 of 10 polyalkylimide gel, 1 of 2 polyacrylamide gel, and the 5 liquid injectable silicone biopsies. In contrast, all 4 HEMA/EMA biopsies contained collections of pDCs in lymphocytic infiltrates close to filler particles and adjacent sarcoidal granulomas. CONCLUSIONS: Our data suggest that pDCs contribute to the sarcoidal granulomas associated with injected HEMA/EMA. Recruited pDCs may exert their pro-inflammatory effects by the release of interferon-α at the site of these filler deposits.

Complications After Facial Injections With Permanent Fillers: Important Limitations and Considerations of MRI Evaluation.

BACKGROUND: Soft-tissue fillers have become more prevalent for facial augmentation in the last 2 decades, even though complications of permanent fillers can be challenging to treat. An investigative imaging tool could aid in assessing the nature and extent of these complications when clinical findings are ambiguous. OBJECTIVES: The authors analyzed the value of magnetic resonance imaging (MRI) in the assessment of delayed-onset complications after injection of patients with permanent fillers. METHODS: Thirty-two patients with complications related to facial fillers were evaluated in this prospective cohort study. Their medical history was documented, and MRI was conducted before treatment of the complications. Radiologists were informed of the injection sites but were blinded to the results of other clinical evaluations. Levels of agreement between clinical and radiologic findings were calculated with the Jaccard similarity coefficient. RESULTS: A total of 107 site-specific clinicoradiologic evaluations were analyzed. The level of agreement was assessed as strong for deposits without complications and noninflammatory nodules (combined 85%), moderate for abscesses (60%), fair for low-grade inflammations (32%), and slight for migrations (9%). Results from the MRI examinations aided in subsequent treatment decisions in 11% of cases. CONCLUSIONS: Study results show that MRI may be useful for diagnosing complications associated with fillers that have migratory potential, for depiction of the extent of deposits before treatment, and for follow-up of low-grade inflammation and abscesses after surgery. LEVEL OF EVIDENCE: 3.

Semipermanent filler treatment of HIV-positive patients with facial lipoatrophy: long-term follow-up evaluating MR imaging and quality of life.

BACKGROUND: Injectable fillers such as poly-L-lactic acid (PLLA) and calcium hydroxylapatite (CaHA) have shown promising results in the treatment of combination antiretroviral therapy (cART)-induced facial lipoatrophy (FLA). However, the effects of these substances on magnetic resonance imaging (MRI) have not yet been described. OBJECTIVE: The authors analyze the association between the effects of treatment with semipermanent fillers on MRI and changes in quality of life (QOL). METHODS: Eighty-two human immunodeficiency virus (HIV)-positive patients with cART-induced FLA (grades 2-4) were enrolled in this prospective study. A mean volume of 58.2 mL (range, 12-105 mL) of PLLA (n = 41 patients) and 9.1 mL (range, 3-23 mL) of CaHA (n = 41) was injected in multiple sessions. The MRI examinations were performed prior to treatment and again 12 months after. The self-reported severity of FLA as well as QOL was measured using questionnaires based on Short Form 36, Medical Outcomes Study HIV Health Survey, and Center for Epidemiologic Studies Depression Scale formats. RESULTS: Significant increases in total subcutaneous thickness (TST) of the injected regions could be identified on MRI in nearly all patients 1 year posttreatment. Patients reported that mental health and social and role functioning improved; depressive symptoms decreased after treatment. In addition, the increase in TST was positively associated with improvement of QOL. CONCLUSIONS: This study confirms that treatment with both PLLA and CaHA not only increases TST but also is associated with improved QOL for HIV-infected patients. Furthermore, the study also demonstrates that MRI can show filler-induced neocollagenesis and quantify FLA treatment effects.

Delayed-onset complications of facial soft tissue augmentation with permanent fillers in 85 patients.

OBJECTIVE: To evaluate factors influencing the onset and type of adverse events in patients injected with permanent fillers in the face and to propose a therapeutic strategy for these complications. METHODS: A prospectively attained series of 85 patients with delayed-onset complications after facial injection with permanent fillers underwent clinical follow-up and treatment of the complications. RESULTS: Lag times until onset and type of delayed-onset complication varied according to filler material. In 28% (n = 24) of the cases, patients reported the onset of complications after dental procedures, additional injections with fillers, or other invasive treatments in the facial area. Forty-eight (57%) patients required invasive treatment. Abscess formation was significantly more frequent in patients with human immunodeficiency virus infection and facial lipoatrophy (p = .001). CONCLUSION: The intrinsic characteristics of the injected filler and the immune status of the patient play important roles in the diversity of time of onset and type of delayed-onset adverse events observed. It seems that invasive facial or oral procedures in the vicinity of filler depots can provoke such complications. We propose a strategy for treating these complications and advise great caution when using permanent filling agents.