Prepackaged injectable fi llers are extremely safe and widely used. As a consequence, it is dif fi cult to know whether the few rare effects reported are truly related to the fi llers or incidental, unrelated fi ndings in patients who happen to have received augmentation. Additionally, each fi ller material
has speci fi c recommendations for injection tech- nique that can minimize problems with use; for example, poly- l -lactic acid is a thick, heteroge- nous solution that clogs needles and syringes, which consequently need to be frequently changed to avoid inadvertent placement of exces- sively large aliquots into the skin.
Relatively commonly reported undesired effects that are dif fi cult to ascribe to fi llers them- selves include headache, sinusitis, and other respiratory symptoms. These may be a sign of concurrent unrelated mild illness or respiratory infections. In some cases, headache may result from the injection process itself: it has been shown by others that needling of the forehead in the absence of injection of any material can occa- sionally induce headache.
2.3.1 Infection
Itch, acne, and herpes simplex virus reactivation (e.g., “cold sores”) have been reported in a few instances and may be associated with inadvertent skin irritation during the injection process.
However, these effects may also be unrelated and reported by patients only because they incorrectly believe them to be related. Cutaneous bacterial infection and resulting scar may rarely be associ- ated with extrusion of super fi cially placed implants. Management of implant-related infec- tion entails use of topical and oral antibiotics;
scar is best managed by prevention.
Signi fi cantly, reuse of fi ller material beyond the date of package opening does not appear to be associated with short-term or long-term risk of infection. As it may be cost-effective for a patient to use leftover material later, this has practical implications. Two separate research groups have empirically assessed the risk of contamination in reused packages and have not detected any loss of sterility [ 26, 27 ] . An allied concern is that so- called bio fi lms in human skin may contain infec- tious agents that can interfere with fi ller placement and render fi llers more likely to induce subclini- cal infections [ 28 ] . This remains an active area of debate and research. Nonetheless, as a precau- tion, the makers of calcium hydroxylapatite
(BioForm/Merz) no longer advocate placement of fi ller injections through the oral mucosa.
2.3.2 Systemic Illness
Rare, serious effects that have been seen in patients treated with fi llers include collagen vas- cular disease and facial nerve palsy. The infre- quency of reports of these makes it impossible to speculate regarding their etiology or causal con- nection to fi ller materials.
2.3.3 Injection-Site Necrosis
One rare but serious undesired effect that may be causally related to injection of fi ller materials is injection-site necrosis (Fig. 2.8 ) [ 29 ] . Observed rarely after glabellar or perinasal injections, this has been traced to the proximity of medium-cali- ber local vasculature, which can be tamponaded or occluded. Speci fi cally, inadvertent injection of the angular artery (nasolabial fold area) or supra- trochlear artery (glabellar area) with viscous fi llers induces an ischemic response with viola- ceous bluish-gray discoloration, pain, erosion, and ulceration [ 30 ] . While the clinical presenta- tion can vary from a diffuse pink blush to a retic- ulated red-brown erythema, the startling appearance does not usually presage serious problems. Most cases are localized and transient, with a few cases of residual hyperpigmentation that remits. Current fi ller injections have not been implicated in embolic phenomenon resulting in retinal artery thrombosis, one case of which was reported in the distant past following use of Zyplast collagen.
That being said, uncommon but more severe cases of injection-site necrosis can result in full- thickness skin slough, scar, and permanent dis fi g- urement. There does not appear to be any speci fi c way to avoid these more serious complications, which usually manifest with signi fi cant discom- fort and are believed to be associated with arterial occlusion. Recommendations to “pull back” on the injection syringe prior to injection are not practical, given the very fi ne caliber of the nee- dles typically used and the limited amount of
back pressure that can be created in a pre fi lled syringe. Probably the most useful recommenda- tions are to inject relatively super fi cially in the subcutis and, when injecting in an anatomic region of concern (i.e., nasolabial, glabellar, etc.), to inject slowly at a rate of approximately 0.3 cc/
min. Slow injections are less likely to reverse the intravascular pressure and permit retrograde movement of fi ller into the vessel.
Should occlusion of a vessel occur, the fi rst step is to recognize the problem. Flushing the affected area with saline may diminish vascular tamponade associated with adjacent but not intravascular fi ller injection. If a linear thread consistent with vascular occlusion is seen, man- ual pres sure can be exerted to push the fi ller back out of the vessel. In the case of hyaluronic acid injections, hyaluronidase should be injected into the affected site. While some advocate the use of vasodilators, such as nitroglycerin ointment, there is limited evidence of their ef fi cacy. Hyperbaric oxygen may potentially be of therapeutic utility and has been used by some practitioners. Past the acute phase, treatment is conservative. Hyaluro- nidase may again be injected upon follow-up, but in general, this is a period for reassurance and
“hand-holding.” Patients may be eager for inter- ventions, but they should be reassured that much of the persistent redness, swelling, or crusting of their face will spontaneously heal and that aggres- sive measures may worsen the fi nal outcome.
Fig. 2.8 Early necrosis associated with hyaluronic acid fi ller occlusion of lip vasculature. This may subsequently ulcerate and heal with scarring
Mild topical steroids may be of use both to reduce in fl ammation and to provide anxious patients with a relatively harmless therapeutic intervention.
2.3.4 Compatibility with Laser and Energy Devices
Another potential adverse event is alteration or degradation of injectable fi llers due to treatment of the overlying skin with lasers, lights, and energy devices. Speci fi cally, it has been sug- gested that nonsurgical tightening by deeply pen- etrating radiofrequency modalities may result in heat delivery that may cause liquefaction, migra- tion, or destruction of injectable implants. At least one human study has found this not to be the case, with biopsies of recent hyaluronic acid injections showing that these are unaffected by monopolar radiofrequency treatment; the cos- metic effect of calcium hydroxylapatite injections may actually be augmented by the same treat- ments [ 31 ] . Another trial has extended these fi ndings, trying virtually every type of available cutaneous energy device to disrupt hyaluronic acid injections immediately after placement but not fi nding evidence of any such disruption [ 32 ] .
2.3.5 Problems with Permanent Fillers
Long-lasting or potentially permanent fi llers are not commonly used in the USA but may be used more often in Canada, Europe, South America, and Asia. At present, the only two permanent fi llers in use in the USA are liquid injectable sili- cone and poly(methyl methacrylate) (PMMA) microspheres suspended in 3.5% bovine collagen solution; part of the reluctance to use longer-last- ing and permanent fi llers stems from the concern that complications, if they arise, may be similarly persistent.
Silicone may be injected as oil (Silikon 1000) that is approved for intraocular tamponade after retinal detachment and used off-label as a cutane- ous fi ller. Local reactions such as pain, swelling, and ecchymosis are common in the immediate aftermath of injection. Rarely, indurated areas of
the skin and in fl ammatory nodules and granulomas may also appear after silicone injection. These prob lems may occur years after the initial injection [ 33 ] and are dif fi cult to treat. Modest improve- ment has been reported with topical application of imiquimod, intralesional injection of corticoster- oids, and oral minocycline [ 34, 35 ] . In the USA, to minimize the risk of such complications, many conservative practitioners use liquid silicone mostly for treatment of acne scarring, which requires small aliquot injections, and for patients with HIV- associated lipoatrophy. In selected cases, it may be appropriate to apprise patients of the potential long- term risks prior to treatment.
PMMA microspheres suspended in 3.5%
bovine collagen solution (Arte fi ll) have been available in Europe and Canada in the current or antecedent versions since the mid-1990s. Since the early days, the material has been improved, with the spheres produced now being of much more uniform size. After this fi ller material is injected into the skin, the bovine collagen phase of the implant is degraded and resorbed, and the PMMA component is left behind. The PMMA microspheres persist and induce a granulomatous foreign body reaction, which elicits formation of a fi brous capsule shell around them. This combi- nation of spheres and fi brous tissue collectively results in fi lling of the targeted soft-tissue defect.
Adverse reactions, which include telangiectasia, hypertrophic scarring, allergic reactions, and hypertrophic scarring, can appear months to years after injections. Super fi cial placement or use of excess product can induce visible small nodules or ridges. Treatment of such textural imperfec- tions is dif fi cult, and while intralesional steroid injections have been reported to be successful, one of the authors (N.S.) fi nds that even multiple treatments usually result in only partial resolu- tion. In resistant cases, surgical extraction or excision may be necessary [ 36 ] .
Conclusion
Overall, prepackaged injectable soft-tissue augmentation materials are extremely safe and well-tolerated materials that provide many options for facial rejuvenation. Undesired effects tend to be minor and prone to sponta- neous resolution resolve within a few days to
a week. Rare is the patient who encounters more than mild discomfort, with possible tran- sient redness, swelling, and bruising. Lumps and nodules occur infrequently, are usually easily treated, and are only rarely associated with immune responses or cutaneous hyper- sensitivity. Discussion of bene fi ts and risks with patients before injection, coupled with a thorough understanding of the speci fi c tech- niques required for the use of particular fi llers, should enable surgeons to use these materials with few problems.
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