Delayed filler complications are thought to be related to biofilms. Biofilms are heterogeneous structures of bacterial colonies with an adherent extracellular matrix, which can evade an immune response.46 The clinical picture of a granuloma may be challenging to distinguish between inflammatory and biofilm; however, reports of delayed granulomas with preceding infectious event support an infectious diagnosis.43 Algorithms have been established to aid in the diagnosis and proper management of this presentation.38
The best management of a complication is prevention. Injectors should understand the anatomy, product, and indications for use. The FDA has set guidelines for approved use of a certain product; however, off label use is still acceptable based on clinical judgment. The author recommends aseptic technique during injections and uses chlorhexidine skin prep to decrease bioburden.
Appropriate placement can minimize palpable lumps or nodules; however, despite appropriate technique, contour irregularities may develop.39 Injection technique is dependent on injector preference and anatomical region. For superficial injections, a linear threading technique is advocated with small aliquots of product in an anterograde and retrograde fashion. Fanning or crosshatching may also be advised to allow even distribution of product. With deeper placement, a depot injection technique has been traditionally recommended.47 However, it has been the experience of the senior author that depot injections are more likely to develop delayed granulomatous reactions.48 Towering or thin layering can be used for deeper placement.49 One must always be cognizant of the needle tip location to prevent inadvertent placement. Lastly, anatomy and facial danger zones must be respected to ensure safe delivery in the targeted plane.
Complications are best managed with early recognition. For erythema, edema, and bruising, cool compresses should be used. Patients should avoid exercise for 24–48 hours to prevent progression. For early lumps and bumps that are related to inappropriate filler placement, gentle massage can be instructed. For refractory lumps, Tyndall effect, or overcorrection, hyaluronidase can be used to dissolve the product.50
Hyaluronidase is a naturally occurring enzyme that breaks down autologous HA and is used for the degradation of HA-based filler product. Human and animal formulations are available but differ in their preparations.51 Hypersensitivity reactions have been reported.52 The senior author uses Hylenex (human recombinant hyaluronidase) (Halozyme Therapeutics, San Diego, CA) to dissolve HA products. Vitrase (Bausch + Lomb, Rochester, NY) is the other available hyaluronidase available and is made from sheep testes. The dose is titrated to effect. Clinical effects are immediate if injected directly and can be enhanced with massage.
Intravascular filler injection represents the most severe complication from filler use. Injection should be stopped immediately for any suspicion of vascular compromise. The mainstay of treatment is hyaluronidase. This should be injected diffusely within the ischemic tissue.53 It is not necessary to inject hyaluronidase intravascularly as the product will diffuse widely, even within local vasculature. It should be injected along the course of the artery involved and titrated to effect.23 Additionally, warm compresses, aspirin, and hyperbaric oxygen have been advocated.54
The embolic phenomenon is the etiology of blindness and is related to retrograde flow into the central retinal artery.55 Majority of ocular complications result from injection near the glabella.56 Unfortunately, visual recovery after embolic phenomenon is very poor as irreversible retinal damage occurs within 60–90 minutes.57 If vision loss occurs, expert consultation with an ophthalmologist is mandatory. Retrobulbar injection of high doses of hyaluronidase is recommended to decomplex both intravascular HA and HA in surrounding tissues. Additional treatment modalities include anterior chamber paracentesis, ocular massage, mannitol, or interventional radiologic injection of hyaluronidase within ophthalmic circulation; however, none of these modalities have been shown clinically to be effective.58
Inflammatory nodules, also called granulomas, should be approached in an algorithmic manor (Fig. 4). If fluctuance is present, it should be aspirated and sent for culture. Cultures should be followed up to 21 days as atypical microorganisms may be present. A trial of antibiotics is recommended with dual drug modality such as a quinolone and a macrolide (eg, ciprofloxacin 500 mg twice daily and clarithromycin 500 mg twice daily) for 2 weeks. Hyaluronidase should never be injected with an active infection due to the risk of spreading infectious material within adjacent tissue. If no improvement, and a HA-based filler was used, hyaluronidase can be injected. If a non-HA product was used, or hyaluronidase was ineffective, intralesional triamcinolone can be given. Starting dose is 0.1 mL with 10 mg/mL concentration and titrating to effect.59 One must be careful with superficial placement as atrophy may result. 5-Fluorouracil is another intralesional treatment option but is considered second line.45 Excision should be the last in the treatment algorithm.43
It is clear that HA-based filler products have their place in nonsurgical facial rejuvenation. Understanding basic gel properties and unique filler manufacturing process can help with the selection of an individual product and lead to more predictable results. With the plethora of products available, it is important to understand the applicability and limitations of each facial subunit injected. Safety is always of the upmost importance to minimize complications. Prevention is the key; however, if complications arise, an algorithmic approach is pivotal to success.
The patient who appears in the associated videos provided written consent to be filmed.
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