Jacqueline M. Junkins-Hopkins, MD Based on the dialogue ‘‘Filler complications’’ between Naomi Lawrence, MD, and Susan Weinkle, MD
Dialogues in Dermatology, a monthly audio program from the AmericanAcademy of Dermatology, contains discussions between dermatologists on timely topics. Commentaries from Dialogues Editorin-Chief Jacqueline M. Junkins-Hopkins, MD, are provided after each discussion as a topic summary and are provided here as a special service to readers of the Journal of the AmericanAcademy of Dermatology. ( J Am Acad Dermatol 2010;63:703-5.)
Since ﬁllers were introduced for facial rejuvenation more than 20 years ago, a number of substances have been approved by the US Food and Drug Administration (FDA) for the correction of facial wrinkles and folds, acne scars, and for subepidermal implantation for correction of lipoatrophy.1 Additional indications recently investigated by the FDA include the use of fillers for augmentation and contouring. Fillers may execute their effect as a volumizer, or as a stimulator, in which microparticles in a degradable polymer gel induce a host response that fills the defect.2 Collagen, hyaluronic acid, and polyacrylamide gels act as volumizers. These are hydrophilic and act as a sponge, absorbing water from the surrounding tissue. Combination gel fillers include poly-L-lactic acid microparticles suspended in sodium carboxymethylcellulose, mannitol and water, calcium hydroxylapatite microspheres suspended in glycerin and carboxymethyl-cellulose, polymethyl methacrylate microspheres suspended in collagen gel, polyhydroxyethyl methacrylate/ ethylmethacrylate fragments suspended in hyaluronic acid gel, and polydimethylsiloxane fragments suspended in collagen gel. Each has its own expected host tissue interaction. Hyaluronic acid and polyacrylamide gel interact with the host to form a vascular fibrous network. Hyaluronic acid disappears within 3 to 12 months, while polyacrylamide remains indefinitely. Combination gels have an ongoing foreign body reaction, contributing to the development of a fibrous network around the particles, which partially replaces the filler defect as the carrier gel disappears in 1 to 3 months. Microparticles of poly-L-lactic acid and calcium hydroxylapatite degrade over months to years. The size, shape, and surface topology of the microparticles also help dictate the volumizing properties and the type and extent of host reaction.3 For instance, larger particles migrate less often, particles with sharp angles may induce a more exuberant fibrotic reaction, and hyaluronic acid has anticoagulant properties that may make it more susceptible to bruising.
As we heard in this dialogue, many of the adverse events associated with ﬁllers are associated with improper injection technique. Increased experience and familiarity with the properties of each product and with facial anatomy will help diminish the risk of complications associated with injecting dermal ﬁllers. Expected procedure-related adverse events, such as tenderness, pain, and bruising may in part be caused by improper technique. Similarly, lumps, nodules, overcorrection, migration, and Tyndall effects (blue lumps or worms associated with superﬁcial placement of hyaluronic acid) may be seen more frequently with the novice injector. More concerning complications include allergic and granulomatous reactions to the product, the reactivation of herpesvirus infections, bioﬁlms, acute infections, nerve palsies, and vascular complications, such as blindness caused by embolism and necrosis from inadvertent intravascular ﬁller injection, direct vascular injury, or the compression of vessels by the ﬁller. Some of these complications are unpredictable, but measures can be taken to avoid some of these
1,3-7 events.One should be cautious if there is a history of bleeding disorders or ingestion of aspirin, warfarin, ginseng, vitamin E, or herbal supplements with anticoagulant effects. Prophylactic antivirals should be prescribed if there is a history of herpesvirus infections. Awareness of the hydrophilic nature and the viscosity of each hyaluronic acid product may help avoid edema, nodules, and overcorrection. This unanticipated volume expansion may also result in vascular compression, especially when used in small spaces. Injecting small amounts of filler may reduce this risk. Experience will help the injector place the filler in the appropriate plane, in order to avoid blue lumps of superficial hyaluronic acid. Lumps occur more often in the tear trough, lips, and lids. Puncture with a No. 11 blade with expression of gel, the injection of hyaluronidase to dissolve the filler, and massage will help reverse some of the undesired injected filler placement.
Familiarity with the danger zones and facial anatomy is crucial. Injection into the glabella should be done with caution, because this site has limited collateral circulation. Vascular compromise causing necrosis and rarely blindness is typically reported at this location. Protocols for prevention and treatment have been published.7 Aspiration before injection, using small aliquots of filler, and injecting superficially and medially may decrease this risk. Direct arterial embolization of filler can be recognized by immediate, often severely painful geographic blanching. Treatment options include attempted aspiration, vigorous massage, application of 2% nitroglycerin paste, injection of hyaluronidase, and warm compresses. Venous occlusion is often delayed, and presents as a dull pain with bluish discoloration that may simulate a bruise. If this scenario continues beyond 2 weeks, one should consider this diagnosis. Alar necrosis is a recognized complication that is possibly caused by the compression of branches of the facial artery from hyaluronic acid
Nodules may be inﬂammatory or noninﬂammatory and infection-or noninfection-related.3,5 Nodular complications occurring earlier than 2 weeks are likely related to incorrect filler placement, but pain and fluctuance may indicate infection. Intermediate to late nodule complications, arising 2 weeks to 1 year postinjection, and delayed nodules noted beyond 1 year, may be immune responses to the filler or infectious granulomas. Delayed onset fibrotic nodules may be seen with poorly placed particulate stimulatory filler, such as poly-L-lactic acid and calcium hydroxyl apatite, especially in mobile areas, such as the lip, or with the use of poly-L-lactic acid, particularly because of the inadequate dilution of filler. These are treated with massage, dilution with saline, and intralesional steroids. Steroids should not be used for tender or inflammatory nodules unless there has been treatment with antibiotics. True granulomas are differentiated by tenderness, swelling, and at times, fluctuance, but histologic documentation may be required. Granulomatous nodules are seen on the lips with calcium hydroxylapatite, usually within 12 weeks, while poly-L-lactic acid gel has a higher frequency of granulomatous nodules that may appear simultaneously at all injected sites many years postprocedure.2 Nodules caused by nondegradable polymehthyl methacrylate microspheres may also present many years postprocedure. Histologically, there is a sarcoidal granulomatous reaction with a variably mixed inflammatory infiltrate. The micro-particles have characteristic shapes that may help identify the filler subtype. Infection should be excluded. However, proving an infection may be difficult, often requiring polymerase chain reaction analysis or fluorescence in situ hybridization to document the organism. Polyacrylamide gel is susceptible to bacterial infection, and low virulence normal flora bacteria introduced during injection has been documented in several cases with this filler.2 Steroid injection to treat presumed fibrous nodules may initially improve the symptoms of an infectious nodule while also promoting quiescent bacterial growth adherent to the inert surface and encapsulated by a self-developed protective polymeric matrix.2,9 These biofilms are self-sustaining colonies that have reduced metabolism allowing antibiotic resistance and genetic alterations that allow escape from the immune system. In the early stage of biofilm development, the culture is negative. Bacteria from dental work, trauma, steroid injection, or the reinjection of filler over a previously treated site may activate biofilms, creating an acute purulent infection or a subacute granulomatous reaction. Inflammatory nodules caused by biofilms should be treated with antibiotics for several weeks, and often more than one antibiotic is needed. Clarithromycin or minocycline for 6 weeks has been suggested for early infections that are presumed to have been caused by biofilm activation.3 After the patient has begun antimicrobial therapy, evacuation of the filler by incision and drainage or surgery or the injection of hyaluronidase will often be required to clear and prevent recurrence of the infection and biofilm.
As we heard in this dialogue, the procedure of injecting dermal ﬁllers should be approached as one would a surgical procedure, with appropriate prepping and detailed knowledge of the facial anatomy. This may help prevent the development or activation of bioﬁlms. The best way to manage complications is to avoid them. Knowledge of the unique characteristics of the ﬁller gels and injection experience will also help to diminish the risk of adverse events or undesirable outcomes.
1 US Food and Drug Administration. Center for Devises and Radiological Health. Executive summary. Dermal filler devices. November 18, 2008. Available at: http://www.fda. gov/ohrms/dockets/ac/08/briefing/2008-4391b1-01%20-%20FDA %20Executive%20Summary%20Dermal%20Fillers.pdf. Accessed August 4, 2010.
2 Christensen LH. Host tissue interaction, fate, and risks of degradable and nondegradable gel fillers. Dermatol Surg 2009;35(suppl 2):1612-9.
3 Narins RS, Coleman WP, Glogau RG. Recommendations and treatment options for nodules and other filler complications. Dermatol Surg 2009;35(suppl 2):1667-71.
4 Weinberg M, Solish N. Complications of hyaluronic acid fillers. Facial Plast Surg 2009;25:324-8.
5 Sclafani AP, Fagien S. Treatment of injectable soft tissue filler complications. Dermatol Surg 2009;35(suppl 2):1672-8.
6 Winslow C. The management of dermal filler complications. Facial Plast Surg 2009;25:324-8.
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1 Glaich AS, Cohen JL, Goldberg LH. Injection necrosis of the glabella: protocol for prevention and treatment after use of dermal fillers. Dermatol Surg 2006;32:76-81.
2 Grunebaum LD, Allemann IB, Dayan S, Mandy S, Baumann L. The risk of alar necrosis associated with dermal filler injection. Dermatol Surg 2009;35(suppl 2):1635-40.
3 Monheit GD, Rohrich RJ. The nature of long-term fillers and the risk of complications. Dermatol Surg 2009;35(suppl 2): 1598-604.
Additional topics from the September 2010 issue of the Dialogues in Dermatology:
1 Nanotechnology With Adnam Nasir, MD, PhD, interviewed by Maurice Thew, MD
2 Infection in HIV Patients With Carrie Kovarik, MD, interviewed by Gary Brauner, MD
Dialogues in Dermatology is published monthly by the American Academy of Dermatology in CD and online formats. Corporate and editorial offices: 930 E Woodfield Dr, Schaumburg, IL 60173-4729. 2010 subscription rates: $200 for individuals in the United States, Canada, and Mexico for CD format; $159 for individuals in the United States, Canada, Mexico, and international for online format. ª 2010 by the American Academy of Dermatology, Inc. Subscriptions are available by calling toll-free: (866) 503-7546 or faxing (847) 240-1859. Additional information is available in the Marketplace section of www.aad.org.