Insufficient experience is a contributory factor in the development of complications.18 Clinicians should seek appropriate product selection and practice proper techniques to minimize adverse reactions. Clinicians performing injections should have a thorough knowledge of injection-related anatomy and, before treatment, elicit a full history of previous cosmetic procedures to determine whether relative or absolute contraindications exist. Specifically, the clinician should query the patient regarding previous complications with dermal fillers, significant allergy, or other significant medical conditions. The list of the patient’s medications should be reviewed.
Product selection is important, as the safety profiles of dermal fillers may vary.19 Importantly, the physical and rheologic properties of the filler should fit the intended intervention. For example, products with a higher elastic modulus (G′) are not recommended in delicate areas such as the tear trough.
Hyaluronic acid fillers can be delivered safely and efficaciously by either cannula or needle if used appropriately. However, the panel recommended that needles be used with caution in areas prone to vascular complications. The use of blunt cannulas may be more appropriate in these regions. However, the panel stressed that no single injection technology is completely safe. Operator technique is more important with regard to safety (Table 2).
The validity of anterograde and retrograde injections was recognized by the panel, and it was strongly recommended that clinicians aspirate with a needle or cannula before injection, especially in high-risk areas. However, although positive aspiration is sufficient reason to remove the instrument and reposition, clinicians should not rely on negative aspiration to rule out the risk of intravascular injection.
PREVENTION AND TREATMENT OF EARLY COMPLICATIONS
Pretreatment Antisepsis and Prophylaxis
The panel recommended that the treatment area be cleansed with appropriate antiseptic and the patient’s skin be free of makeup, which should also be avoided following treatment. Evidence supporting specific skin preparation is lacking, and alcohol swab preparation pads are commonly used. General guidelines for reduction of health care–associated infection include effective skin antisepsis using 2% chlorhexidine gluconate in 70% isopropyl alcohol.20,21 Disposable nonsterile gloves and sterile dressing trays and drapes22 are inexpensive and contribute to a hygienic work area as well.
To avoid triggering recurrent herpetic outbreaks, the panel recommended antiviral prophylaxis in patients with a history of herpes infection when injections into vulnerable areas are planned. Injections should be delayed in patients with active herpes lesions until their complete resolution (Table 4).
Vascular Infarction and Compromise
Intravascular injection of filler substances can lead to devastating side effects, such as tissue necrosis and vision loss. (Note: vascular infarction can resemble herpetic outbreaks, and they may be confused.) Vascular accidents are best avoided with knowledge of vascular anatomy (Fig. 1), adequate training, and appropriate technique. Several sources in the literature describe strategies for diminishing this risk.6,7 Precautions include aspiration before injection, slow injection with minimal pressure, and delivery of material at different points and in small volumes per pass. It is important to keep the needle moving. Use of small needles have been advocated by some members of the panel and blunt microcannulas have been advocated by others.
An algorithm for the treatment of intravascular injection is presented in Figure 2. The consensus includes immediate cessation of the injection, hyaluronidase, and massage (with warm compresses if appropriate). Hyaluronidase should be injected immediately and used daily in liberal doses where signs and symptoms are present (e.g., livedo reticularis–like appearance, pustulation, well-demarcated erythema, pain on injection or in the days following) and wherever the vasculature appears compromised, not only at the site of injection (“flood the field”). A recent bench study supports injection of hyaluronidase diffusely into ischemic tissue.23 As hyaluronidase is useful in the management of many complications that may arise from hyaluronic acid fillers, clinicians should always have it readily available if permitted by local regulatory or legal statutes. However, injectors should always bear in mind the possibility of allergic reactions following its use.24
For intravascular infarction, the panel recommended injection of a minimum of 200 to 300 U of hyaluronidase (spread over the entire area of impending necrosis), repeated daily for a minimum of 2 days until signs of permanent necrosis or reestablished blood flow appear. Doses up to 1500 U were suggested if needed, because the consequence of inadequate dosing is tissue necrosis. The patient should be reassessed every 24 hours. If infection arises, antibiotic therapy should be started immediately. Use of topical nitroglycerin (1%) paste is also recommended in cases of obstruction (Table 4). Other strategies (without proven efficacy) include systemic or topical steroids, aspirin, low-molecular-weight heparin, hyperbaric oxygen, and intravenous prostaglandins. Measures to improve retinal perfusion described in the literature (albeit with limited success) include immediate ophthalmologic consultation, ocular massage, timolol eye drops, hyperbaric therapy/oxygen, diuretics, systemic and topical corticosteroids, anticoagulation, and needle decompression of the anterior chamber.6
Treatment of hyaluronic acid filler–related hypersensitivity depends on severity. In many cases, it may be self-limiting and resolve spontaneously after a few hours or days. Swelling may respond to antihistamines if mast cell–mediated. Oral steroids are the mainstay of treatment for persistent edema or edema that does not respond to antihistamines. Rapidly progressing angioedema should be considered a medical emergency because of possible airway obstruction. Delayed hypersensitivity reactions usually resolve without sequelae, but depending on the presentation, oral steroid treatment may be required.5,7 If possible, the allergen should be removed.
Early Acute Infection
The panel recommended a hierarchy or sequence of treatment options for early acute infections, as follows: antibiotics (empiric), then consider hyaluronidase, then consider steroids. An algorithm for the treatment of mild to moderate early and late complications is presented in Figure 3.
Antibiotic therapy should be prescribed if signs or symptoms of acute bacterial infection are present; clinical judgment should guide subsequent decisions to save the implant for aesthetic correction or inject hyaluronidase to avoid recurrence of infection. A multiprong approach using both antibiotics and antiviral agents is reasonable when the cause is uncertain and laboratory support is lacking.22
Culture-directed antibiotic selection is impractical for initial therapy. The recommended initial empiric therapy for both fluctuant and nonfluctuant infections includes amoxicillin plus clavulanate, or cephalexin, or in the case of penicillin allergy, ciprofloxacin. For abscesses, incision and drainage or aspiration remains the tenet of proper surgical treatment. If empiric antibiotic therapy is unsuccessful, culture-directed therapy should be considered. Subsequent use of hyaluronidase may be considered when the infection is quiescent. If infection is clinically present, hyaluronidase should only be injected in association with antibiotic treatment to avoid spreading the infected material. Overt and covert infection should be ruled out before injection of intralesional steroids is considered for inflammatory nodules.
Appropriate injection techniques help limit the risk of adverse reactions and contour irregularities.8 Increased dissection of the subepidermal plane may be related to local adverse events25; however, in the panel’s opinion, there is insufficient evidence to conclude that a specific modality is associated with more complications.
To help minimize bruising and bleeding, practitioners should use clinical judgment in advising patients to temporarily discontinue immune modulators, anticoagulants, and/or drugs or supplements with anticoagulant properties before treatment. (Note: anticoagulation should not be discontinued without consultation with the treating physician.) Injections are only relatively contraindicated in patients taking therapeutic anticoagulants, as meticulous slow-injection technique using small needles/cannulas and immediate prolonged pressure will limit bruising.
Following treatment, it is generally advisable to avoid strenuous exercise for 24 hours to reduce the risk of bruising and swelling. Other steps include using the smallest gauge needle practicable or blunt cannulas, slow injection of small aliquots, avoiding reinjections in the same areas to avoid lidocaine-induced vasodilatation, and limiting the number of transcutaneous puncture sites. Immediate application of pressure rather than cold therapy remains the mainstay of bruising prevention; however, cold compresses may be used.15 Some panel members noted use of pulse dye laser if bruising appears.26
Lumps, asymmetries, or contour deformities occurring in the early posttreatment period may respond to massage. Needle aspiration or minimal stab wound incision with evacuation may be options. A benefit of hyaluronic acid fillers is that irregularities can be reversed with hyaluronidase, a feature that fillers of other types do not share.5,7,9,22 However, considering the risk of possible allergic reactions, its use should be limited. Appropriate technique will allow use of the enzyme in emergencies only. The panel recommended the following hyaluronidase schema:
- Less than 2.5-mm area: 10 to 20 U single injection; repeat injection if required.
- Area of 2.5 mm to 1 cm: two to four injection points with 10 to 20 U per injection point; repeat injection if required.
However, the panel indicated that physicians should use clinical judgment while the dosage is titrated to effect. Indeed, the units of hyaluronidase required to dissolve a given amount of hyaluronic acid also depend on the product itself. Not all hyaluronic acids on the market respond equally to hyaluronidase.27 Treatment of edema and of the Tyndall effect, which may follow lower eyelid applications, consists of injecting hyaluronidase into the surrounding tissue followed by gentle massage. The schema above can guide dosing. Only modest pressure should be applied to disperse hyaluronidase over the area.
TREATMENT OF LATE COMPLICATIONS
Displacement of hyaluronic acid filler products, mainly caused by intramuscular placement, can also be treated with hyaluronidase using the same schema above.28
Late Chronic Infections
In the opinion of the panel, a sequence of treatment options similar to that in early acute infection should be followed: antibiotics (empiric), then hyaluronidase, then steroids. Appropriate antibiotic treatment includes a third- or fourth-generation cephalosporin (e.g., cefixime).
Inflammatory Nodules or Granuloma
Sclafani and Fagien advise incision and drainage and antibiotic treatment of fluctuant nodules,9 and empiric antibiotic therapy followed by reevaluation for nonfluctuant nodules; if there is no improvement, biopsy and culture are indicated. The panel recommended the following empiric antibiotic schema: clarithromycin 500 mg plus moxifloxacin 400 mg twice daily for 10 days, or ciprofloxacin 500 to 750 mg twice daily for 2 to 4 weeks, or minocycline 100 mg once daily for 6 months.
Culture should guide subsequent antibiotic selection. If no diagnosis is made, addition of a macrolide should be considered for an additional 2 to 4 weeks. Once signs of infection subside, consider hyaluronidase and a steroid.
Granulomatous reactions to hyaluronic acid fillers can be treated with hyaluronidase with the dosing described as above. Empiric antibiotic therapy should be considered. Granulomas may respond to oral or intralesional steroids after infection is ruled out or quiescent. An intralesional steroid may be used in combination with hyaluronidase. In cases of repeated failure of other therapies, surgical excision is the treatment of choice for foreign-body granuloma. The literature also contains description of laser-assisted evacuation of filler material and inflammatory and necrotic debris of granulomata.29
Strategies for the treatment of noninflammatory nodules include removal of the causative agent and consideration of empiric antibiotic treatment. Short-term temporary measures such as a steroid may be appropriate in limited clinical circumstances.
The panel stressed the importance of clinical judgment in selecting suitable treatment approaches. For example, hyaluronidase was considered an appropriate option for a single cold nodule of 3 months’ duration. For multiple cold nodules of similar duration, the panel considered a course of antibiotic therapy for several weeks followed by hyaluronidase as the most appropriate approach. Use of short-term systemic steroids was also discussed by some panelists.
OVERALL SUMMARY AND CONCLUSIONS
Because hyaluronic acid fillers are minimally immunogenic and can be enzymatically degraded by hyaluronidase, they have become the most common of the temporary fillers on the market. Hyaluronic acid dermal fillers are today established as the preferred material for minimally invasive cosmetic interventions. However, early and late complications ranging from minor to severe can occur with hyaluronic acid fillers, and the risk profile may be changing as the treatment landscape evolves. Optimal complication management remains an unmet need in the field of aesthetic medicine. The cosmetic physician should be suitably experienced to select and use hyaluronic acid fillers. As such, they should have a detailed understanding of facial anatomy, practice appropriate patient and product selection, and possess knowledge of correct preparation and injection techniques. Most adverse events are avoidable with proper planning and technique. Should adverse reactions occur, the clinician should have the tools available and be prepared to confidently treat them. Proper preparations for emergencies should reduce the severity of adverse outcomes associated with injection of hyaluronic acid fillers in the cosmetic setting.
The authors express their deep appreciation to John F. Kross, M.Sc., D.M.D., of Educational Awareness Solutions, for editorial support.
APPENDIX: GLOBAL AESTHETICS CONSENSUS GROUP
The Global Aesthetics Consensus Group comprises the following faculty members: André Vieira Braz, M.D., dermatology, Rio de Janeiro, Brazil; Jean D. A. Carruthers, F.R.C.S.(C), F.R.C.Ophth., ophthalmology, Vancouver, British Columbia, Canada; Koenraad L. De Boulle, M.D., dermatology, Aalst, Belgium; Steven Fagien, M.D., ophthalmic plastic surgery, Boca Raton, Fla.; Greg J. Goodman, M.D., dermatology, Carlton, Victoria, Australia; Soo-Keun Lee, M.D., Ph.D., dermatology, Seoul, Republic of Korea; Steven Liew, M.B.B.S., plastic surgery, Sydney, New South Wales, Australia; Gary Monheit, M.D., dermatology, Birmingham, Ala.; Hervé Raspaldo, M.D., facial plastic surgery, Cannes, France; Rod J. Rohrich, M.D., plastic surgery; Dallas, Texas; Gerhard Sattler, M.D., dermatology, Darmstadt, Germany; Massimo Signorini, M.D., plastic surgery, Milan, Italy; Hema Sundaram, M.D., dermatology, Rockville, Md.; Arthur Swift, M.D., C.M., plastic surgery, Montreal, Quebec, Canada; Ada R. Trindade de Almeida, M.D., dermatology, Sao Paolo, Brazil; and Yan Wu, M.D., Ph.D., dermatology, Beijing, People’s Republic of China.
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4. Narins RS, Jewell M, Rubin M, Cohen J, Strobos J. Clinical conference: Management of rare events following dermal fillers. Focal necrosis and angry red bumps. Dermatol Surg. 2006;32:426434.
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19. Zielke H, Wölber L, Wiest L, Rzany B. Risk profiles of different injectable fillers: Results from the Injectable Filler Safety Study (IFS Study). Dermatol Surg. 2008;34:326335discussion 335.
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Copyright © 2016 by the American Society of Plastic Surgeons
29. Cassuto D, Marangoni O, De Santis G, Christensen L. Advanced laser techniques for filler-induced complications. Dermatol Surg. 2009;35(Suppl 2):16891695.