COSMETIC

Liquid Injectable Silicone: A Review of ItsHistory, Immunology, TechnicalConsiderations, Complications, and Potential

Rhoda S. Narins, M.D.Kenneth Beer, M.D.

White Plains, N.Y.; and West PalmBeach, Fla.

Summary: For over five decades, liquid injectable silicone has been used forsoft-tissue augmentation. Its use has engendered polarized reactions from thepublic and from physicians. Adherents of this product tout its inert chemicalstructure, ease of use, and low cost. Opponents of silicone cite the many reportsof complications, including granulomas, pneumonitis, and disfiguring nodulesthat are usually the result of large-volume injection and/or industrial grade oradulterated material. Unfortunately, as recently as 2006, reports in The NewEngland Journal of Medicine and The New York Times failed to distinguish betweenthe use of medical grade silicone injected by physicians trained in the micro-droplet technique and the use of large volumes of industrial grade productsinjected by unlicensed or unskilled practitioners. This review separates these twomarkedly different procedures. In addition, it provides an overview of thechemical structure of liquid injectable silicone, the immunology of siliconereactions within the body, treatment for cosmetic improvement including hu-man immunodeficiency virus lipoatrophy, technical considerations for its in-jection, complications seen following injections, and some considerations of thefuture for silicone soft-tissue augmentation. (Plast. Reconstr. Surg. 118 (Suppl.):77S, 2006.)

The search for the ideal filling material hasbeen ongoing for centuries. Various mate-rials, including collagens, autologous fat,

hyaluronic acids, poly-L-lactic acid, and calciumhydroxylapatite, are among the products cur-rently used for this indication. In the past, manymaterials have been injected for soft-tissue aug-mentation including paraffin (mineral oil) andother, nonbiocompatible products. Among thegamut of substances injected, no filling materialhas generated more controversy than liquid in-jectable silicone. Its proponents describe it as anear perfect filling agent with “superiority ofroutinely obtainable corrections and persistenceof results.”1 Opponents of silicone cite its unpre-dictability and believe it should not be injectedinto the human body. Unfortunately for bothphysicians and patients alike, the history of sili-

cone injections has been marred by the suspen-sion of common sense, a lack of standardizationof the mat, impurity of product injected, absenceof guidelines for volumes used, a lack of follow-up, recommendation for intervals between injec-tions, and a host of other confounding factors.Despite the fact that proper and improper injec-tions of silicone result in outcomes that are to-tally unrelated, many discussions of liquid sili-cone equate the horrific effects that occur afterlarge volumes of contaminated or industrialgrade silicone are used by unskilled individualswith data garnered from microdroplet injectionsperformed by reputable physicians with decadesof experience.

This review discusses, compares, and contraststhe differences between the ethical use of liquidinjectable silicone and its misuse. In addition,

From the Dermatology Surgery and Laser Center; Departmentof Dermatology, New York University Medical School; PalmBeach Esthetic Center; and University of Miami School ofMedicine.Received for publication February 2, 2006; accepted May 12,2006.Copyright ©2006 by the American Society of Plastic Surgeons

DOI: 10.1097/01.prs.0000234919.25096.67

Silicone oil (AdatoSil 5000, Silikon 1000) isapproved by the FDA for use in the eye forsevere retinal detachment and is approved foruse during eye surgery to prevent or treatdetached retina. All other uses are “off-label.”

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the history, structure, and complications follow-ing the use of liquid silicone are discussed. Abrief overview of immunologic and technicalconsiderations is be presented. More detaileddiscussions of these topics is presented in a num-ber of useful publications, and an inexperiencedinjector should refer to these references andundergo thorough training with a physicianskilled in silicone injections before beginning toinject patients with this material.2–23

STRUCTURE, PHYSICALCHARACTERISTICS, AND SUITABILITY

FOR BIOLOGICAL APPLICATIONSIn the early 1900s, a British chemist coined the

term “silicone” to describe a large family of syn-thetic polymers containing elemental silicon. Theviscosity of these compounds is a function of thepolymerization and cross-linkage of their mole-cules. They can exist as solids (elastomers), gels,and liquids. The scientific name for liquid siliconeis dimethylpolysiloxane fluid. Siloxanes are com-pounds in which the element silicon is conjugatedwith oxygen and methane. The term itself is amnemonic acronym derived from silicon, oxygen,and methane. The viscosity of silicone fluids ismeasured in centistokes (cS), with 100 cS beingthe viscosity of water. Adatosil 5000 and Silicon1000 have viscosities designated by their trade-mark appellations. They are the only silicone flu-ids approved for use in any indication by the U.S.Food and Drug Administration. Dow Corning 360fluid, which was used widely in the past for soft-tissue augmentation and used today to coat nee-dles, syringes, and intravenous tubing, may or maynot share the same applications, risks, and bene-fits, as the current, more viscous fluids. The resultsand complications noted following the use ofother silicone fluids may or may not be applicableto outcomes obtained using Adatosil 5000 or Sil-icon 1000.

SUITABILITY FOR BIOLOGICALAPPLICATIONS

In many ways, liquid silicone appears to fulfillmost of the criteria for being the ideal implantablesubstance. It is permanent, noncarcinogenic, min-imally antigenic, and does not support bacterialgrowth. Unaffected by exposure to sunlight andmost chemicals, it can easily be heat sterilized. Itsviscosity remains constant throughout the rangeof temperatures experienced by patients. Differ-ent types of silicone products interact in distinctways in biological systems. However, it is importantto note that silicone products are “not chemically

identical or generically equivalent.”24 Differentforms (e.g., elastomers, liquids, gels) of siliconeimplanted into different anatomical sites may havea differing potential for benefits and complica-tions. For instance, granulomas have never beenreported following the injection of liquid siliconeinto the feet23 but have been reported followingfacial injections. Accordingly, the risks and bene-fits associated with different products (i.e., breastimplants) and elastomeric silicones cannot be di-rectly compared with liquid injectable silicone.

Notably absent from this list of virtues is sili-cone’s potential for misuse, adulteration, and sub-stitution. Also absent from the list is the stigmaassociated with silicone misuse. When minisculedroplets of pharmaceutical grade silicone are im-planted at appropriate depths and anatomical lo-cations using the microdroplet technique, theyare encapsulated by a delicate network of fibro-plasia. This results in a structure that is not pal-pable, has the texture of adjacent tissue, and willtypically not migrate.

HISTORYWith the publication of toxicologic informa-

tion in 1948 that found silicone to be “physiolog-ically inert,”25 interest within the medical commu-nity grew because of the need for biocompatiblemedical and surgical materials. Use of liquid sili-cone to improve body contours became popularfirst in Germany, Switzerland, and Japan duringthe 1940s, and thousands of patients were treatedduring that decade. Beginning in the 1960s, liquidsilicone use in the United States was characterizedby two dramatically divergent approaches associ-ated with two diametrically opposite experiences.

The first approach is best represented by theexperience in Las Vegas, Nevada, where enor-mous (up to 2 liters) volumes of Dow Corning 360fluid was, in many instances, contaminated byheavy metals and other impurities. Approximately20,000 to 40,000 individuals were injected underthese circumstances, and the injected areas in-cluded breasts, faces, legs, and buttocks. Largevolumes (750 to 2000 cc) were injected. This eraof indiscriminate injection of impure productended with a consent decree with Dow Corning in1965.26 Silicone was also intentionally adulteratedwith various formulas, including the Sakarai for-mula, to increase inflammation and the fibropla-sia that resulted following injection. The Sakuraiformula mixed olive oil with silicone in an attemptto induce fibroplasias that would prevent migra-tion and, according to Sakurai, was used in over100,000 patients.23 This intentional adulteration

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followed publications in various journals that sug-gested that silicone was nontoxic even whenadulterated.27–29

The second experience with silicone was pio-neered by Norman Orentreich, who developedthe microdroplet technique. This technique wasdeveloped to obtain a more gradual correctionand minimize the complications that had beenseen with large-volume injections. Adherents ofthe microdroplet technique advocate the use oftiny amounts of medical grade silicone to inducea gradual fibroplasia. A review of the literaturefrom this school has significantly fewer complica-tions associated with this technique than are as-sociated with the large-volume injection of impurematerial. When considering silicone as a soft-tissueaugmentation product, it is important to bear thisdistinction in mind.

FORMAL STUDIESIn 1965, a large-scale study was launched by

the Dow Corning Corporation to secure approvalfor liquid silicone by the U.S. Food and DrugAdministration. A highly purified 350-cS siliconefluid (MDX 4-4011) was created and used specif-ically for the study. During the first phase of thestudy, which followed 1300 patients, one instanceof migration was noted in a single patient follow-ing the treatment of lower extremity atrophy withlarge volumes of material. The second phase of thestudy involved 128 patients with severe lipodystro-phy who were also treated using large volumes ofmaterial (average, 21 cc). Severe facial necrosisand panniculitis occurred in several patients inassociation with inflammatory diseases.30,31 Al-though the study suggested that silicone was safeand effective, the study had design flaws that in-cluded a lack of standardization for the frequencyof silicone injections and for the volume of sili-cone injected at each session. Additional designflaws in the study design included a lack of long-term follow-up.3

Silicone usage continues because the alterna-tives to it are less than optimal and are not per-manent. For instance, other absorbable injectablefillers and implants such as poly-L- lactic acid, cal-cium hydroxylapatite, and hyaluronic acids arehelpful in treating human immunodeficiency vi-rus–associated facial lipoatrophy and age-relatedsoft-tissue loss, but they are limited by cost andshort duration of correction. In addition, poly-L-lactic acid must be reconstituted. These limita-tions were and continue to remain some of thereasons that medical grade silicone, injected using

the microdroplet technique, has a niche as a safeand effective alternative to these products.32,33

ONGOING CLINICAL TRIALSA 1000-cS fluid, SilSkin, is currently undergo-

ing phase II clinical trials by physicians at threesites. Legal issues with the Richard James Com-pany have prevented phase III clinical trials fromstarting. Other studies using Silikon 1000 by Drs.Derek Jones, Harold Brody, and Alastair Carruth-ers have been conducted on human immunode-ficiency virus patients.32,33 These studies evaluatesilicone for the treatment of nasolabial creases andhuman immunodeficiency virus–associated lipoat-rophy. Unlike the studies performed decades ago,these studies are more rigorously designed andhave designated areas that are treated, controlledamounts of material injected per session, and nomore than 1 cc per side of the face per month. Inaddition, there is a limited number of injectionspermitted and a well-designed follow-up periodthat will provide data for years after the injectionsare completed. This improved design should pro-duce data that are more objective and scientificallymeaningful. To date, over 1000 patients have beentreated at four centers, with no serious adverseevents noted after 4 years of study. It is hoped thatthis study will provide objective information re-garding outcomes following the use of standard-ized small volumes of medical grade silicone.

TECHNICAL CONSIDERATIONSOnce implanted, liquid injectable silicone is

permanent and, as such, it is much less forgivingand much more technique sensitive than tempo-rary fillers. Specific technical considerations ap-plicable to liquid injectable silicone include theneed to inject miniscule amounts of material at avery precise depth in the subdermal plane. Injec-tions that are too superficial will result in visiblepapules, whereas injections of large amounts ofmaterial in a single session will result in globs ofsilicone that may result in palpable nodules andmay migrate. In addition, the techniques requiredfor proper injections of silicone mandate that mul-tiple injection sessions are planned at monthlyintervals or greater, in contrast to materials suchas hyalurons or collagen, where a single injectionwill usually provide the degree of filling desired.

One other consideration that must be consid-ered if one is contemplating injecting silicone intoone’s patients is that not all malpractice carrierswill cover its use. Before injection of liquid inject-able silicone, it is important to determine whetheryour malpractice policy will cover a claim arising

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from a silicone injection. This is usually on a state-by-state basis. No other agent currently used forsoft-tissue augmentation is as controversial as sil-icone. Although liquid silicone is unquestionablyan excellent filling agent, its use has significantpolitical, public relations, and medicolegal impli-cations for the clinicians who inject it.

INJECTION TECHNIQUE CAVEATSAmong experienced injectors, there is wide-

spread agreement that silicone (1) must be usedin small quantities of approximately 0.01 ml; (2)overcorrection must be avoided; (3) improve-ments must be achieved slowly; and (4) injectionscannot be carried out superficially and materialmust be precisely placed in the deep dermal orpreferably in the subdermal plane. Silicone is sim-ilar to poly-L-lactic acid, with both materials pro-ducing gradual improvement following multipletreatment sessions of material placed in the der-mal-subcutaneous junction. Silicone injectionselicit a mild fibroplastic response, resulting in aslow increase in tissue volume. Although the vol-ume of silicone used is important for the correc-tion obtained, collagen production is at leastequally important to the final outcome. That iswhy it is important to wait some time in betweeninjection sessions and let the fibroplasia takeplace. That way, patients are not overcorrected.

MICRODROPLET METHODThis technique uses tiny droplets of silicone

(0.01 to 0.03 cc) that are deposited into the sub-cutis by a series of injections spaced approximately2 to 10 mm apart. The needle is inserted into theskin, which may be tented up as the microdropletis deposited. Care must be taken to aim the needlemedially, away from the bulk of the cheek, wheninjecting the nasolabial and marionette lines.Many other areas of the face can be treated withmicrodroplet silicone injections. These includethe cheek hollows, midface, glabella, and teartroughs, and the chin, lips, and cheekbones can beenhanced. Application of a topical anestheticcream provides sufficient analgesia for most pa-tients. However, a regional anesthetic block is gen-erally used before injection of the lips. Overcor-rection must be avoided, and injections that aretoo superficial may result in beading. The use ofBecton Dickinson 3/10cc insulin U-100 Syringes(Becton Dickinson, Franklin Lakes, N.J.) has beenadvocated by several experienced silicone injec-tors, but any 1-cc syringe is adequate provided ithas a Luer-Lok attachment to withstand the pres-sure associated with silicone injections. Injections

are typically carried out at 1- to 2-month intervalsusing a 27- or 30-gauge RJ Max Flo needle. Usually,patients need less than 5 cc for total correction,but total treatment volumes as high as 5 to 10 cc(1 to 2 teaspoons) may sometimes be used, espe-cially for human immunodeficiency virus–associ-ated lipoatrophy. This volume of material requiresseveral months to inject. Large volumes of siliconemay increase the risk of serious complications byincreasing antigenic burden.34

INDICATIONSAlthough it is not presently approved by the

U.S. Food and Drug Administration for any soft-tissue augmentation indication, liquid injectablesilicone is presently used in an off-label mannerfor several indications and areas. Many experi-enced silicone practitioners believe that liquid in-jectable silicone is the best filler for the treatmentof flexible acne scars. The glabella, nasolabial, andmarionette folds; cheek hollows; and tear troughsare also excellent candidates for augmentationwith this product. As with injections of any soft-tissue augmentation product, including cross-linked collagens and hyaluronic acids, great careshould be taken when injecting silicone into theglabella area because of the increased risk of ne-crosis with injections into this site. There are noreported cases of necrosis in this area with silicone,possibly because of the small molecular size.

Lip enhancement may be accomplished withpermanent results; however, the risks of compli-cations following trauma, dental infections, andherpetic infections must be considered when in-jecting this area. Chins and cheek bones are alsoamenable to treatment with silicone. Postrhino-plasty deformities, diabetic foot ulcers, and otherfoot problem, such as corns, and congenital facialasymmetries can also be effectively treated withsilicone.

ABSOLUTE CONTRAINDICATIONSBreast augmentation using liquid injectable sil-

icone should not be attempted because the largevolumes necessary will lead to migration, thick-walled cystic spaces, or granulomata. Silicone is con-traindicated for injections into horizontal creasessuch as the transverse forehead rhytides, where theskin is thin and rests against bone, or the mentalcrease, where it frequently results in ridging orbeading.34 The penis, bones, tendons, and cystsshould not be injected with silicone. Intravascularinjections must be scrupulously avoided.

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RELATIVE CONTRAINDICATIONSPatients with chronic inflammatory diseases,

those with multiple allergies, and patients whohave infectious processes in close proximity toinjections—for example, sinus infections (gla-bella) or lip injections (dental caries)—may be atgreater risk for inflammatory complications fol-lowing silicone injections. Medicolegal consider-ations mitigate against injecting silicone into pa-tients who are pregnant. There is no scientific linkbetween collagen vascular diseases and silicone.

The senior author has no problem injectingsilicone into these patients. Physicians with limitedexperience should avoid these injections. In ad-dition, great caution should be exercised whencontemplating injections of silicone into a patientwho has previously been injected with silicone byanother physician or at another location. The rea-son for caution in this latter category of patient isthat in the event of an adverse event, it will beimpossible to determine whether the adverseevent was associated with the prior injection(which may not have been performed with med-ical grade product or with the microdroplet tech-nique) or with the current injections. In mostinstances, the patient will blame the most recenttreating physician for any complication, and onemay find oneself shouldering the liability for in-jections of silicone performed by another practi-tioner. The legal complications and aggravationthat may result from this are not worth the benefitsin almost all circumstances.

COMPLICATIONSThere is a striking contrast between the oc-

currence and severity of complications followingthe improper use of silicone of unknown purityand large volume injected by inexperienced phy-sicians or lay persons and the complications thatfollow injections of pharmaceutical grade siliconeby skilled physicians using microdroplet tech-niques. Treatment of silicone complications usu-ally involves the use of both oral and injectableintralesional corticosteroids and oral antibiotics.Complications associated with silicone injections,as with any soft-tissue augmentation product, maybe divided into those that are serious and thosethat are minor.

MINOR COMPLICATIONSInjection of any filling agent may be followed

by bruising, erythema, and edema, and silicone isno exception. Fulton et al. report that most pa-tients who received silicone injections to the lips

developed bruising.35 Minor complications spe-cific to liquid silicone include textural changes ofthe skin, peau d’orange effect, and a bluish tingeto the skin. In addition, small nodules can occuroccasionally after injections. These complicationsare technique dependent and result from inject-ing too much silicone and/or injecting it too su-perficially. Because it has a neutral pH, siliconeinjections are less painful than many otherinjections.14 In addition, silicone causes lessedema, erythema, and swelling than many otheravailable fillers.14

One complication unique to silicone is knownas “beading.” This occurs when silicone is placedin the superficial dermis and is subsequently en-capsulated by collagen.1 Nodules develop at ratesdependent on the location injected. Fulton et al.reported nodule formation at a rate of 2 percentfollowing silicone injections into the lips (an areaprone to repeated and constant movement.36 Thisrelatively high rate is in marked contrast to theoverall rate of nodule formation of one in 10,000in other studies published.12 In a discussion of thenodules formed following silicone injections, Ful-ton et al. noted that the histiocytic granulomasformed are “similar to the tissue reactions seenwith polylactic acid.”36 The nodules noted by theseauthors were treated with intralesional cortisoneinjections, excision, or observation.

Granuloma formation is not unique to siliconeinjections; it also occurs following the injection ofother injectable materials. In general, a granulo-matous response is a generic immune responsemounted against a foreign body, and siliconegranulomas may or may not be immunologicallydifferent from other granulomas. To date, therehas not been a well-designed study of the immu-nologic differences, including T-helper cell type 1and type 2 populations, between silicone granu-lomata and those of other entities. Such a studywould help to determine whether silicone elicits adifferent immunologic response than other ma-terials and, if so, how they differ.

A single report of a granulomatous rosacea–like syndrome/drug interaction was reported byRapaport.37 This report documented an eruptionthat followed treatment with etanercept in a pa-tient who had been injected with silicone 36 yearspreviously. It is difficult to assess the causality ofthe silicone injections in this instance, and it ispossible that the etanercept simply unmasked anunderlying predisposition for granulomatous ro-sacea in this individual. To our knowledge, thisremains the only report of this type despite severaladditional years of patient exposure to etanercept.

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Bigata et al. reported a single patient who de-veloped granulomas 8 months after silicone injec-tion for cosmetic indications.37 The authors wereunable to determine the type or purity of thesilicone injected in this single case, so it is impos-sible to categorize this reaction as a reaction topure silicone or to an adulterated product. In thiscase, the nodules resolved after 3 years.

Treatments for silicone granulomas have in-volved the use of antibiotics, topical steroids, sys-temic steroids, and the topical immunomodulatorimiquimod.38 In the case report using imiquimod,Bauman et al. report that Aldara resulted in res-olution of silicone granulomas of the lips. Thetype of silicone injected in this case was thought tobe Silicex, a commercial grade silicone that is con-traindicated for injection into animals or humans.

SERIOUS COMPLICATIONSSerious complications such as severe edema of

the area injected and localized discoloration ofthe area injected occur with a frequency of a frac-tion of 1 percent in most studies, although somerecent reports place the rate at 2 percent.35 Pneu-monitis has been reported following large-volumeinjections of impure silicone by an unlicensedpractitioner.39 In this report, an open lung biopsyrevealed lipoid vacuoles.

Other complications, including cellulitis, ul-cerations, migration, and nodule formation, havealso been reported with silicone injections.26 Re-current cellulitis was reported in patients with den-tal abscesses and chronic allergies.40 Silicone mi-gration is thought to be the result of large-volumeinjections, which do not allow encapsulation ofthe material.6 Despite the absence of any scientificlink between collagen vascular diseases and sili-cone, the authors recommend avoiding injectionsinto patients with a known history of collagen vas-cular diseases because of the medicolegal risk thatmight occur with a flare of the underlying diseasein such a patient.

During a U.S. Food and Drug Administration–approved clinical trial (ostensibly a clinically con-trolled situation), the data regarding complica-tion rates were marred by a lack of standardizationfor quantity of material injected and for the in-tervals between injections. One early U.S. Foodand Drug Administration–approved study of sili-cone reported two serious complications. The firstcomplication involved migration of material in apatient treated with large-volume injections of theextremities. The second complication occurred ina patient with Weber-Christian disease, rheuma-toid arthritis, and atypical mycobacterial infec-

tion. This patient suffered facial necrosis that oc-curred some 11 years after her last injection ofsilicone.3 Similar necrosis was reported two pa-tients (one of whom had Weber-Christian diseaseand the other who did not) by Achauer.30

Notably absent from any discussion of siliconecomplications is significant mention of problemswhen the plantar foot is injected. Indeed, Balkinreports 1585 patients treated with silicone over thespan of more than 40 years, with the only com-plication being “some local and generally asymp-tomatic fluid migration occurred in a few overin-jected feet.”23 It is not known whether the lack ofcomplications seen in silicone injections of thefoot is attributable to the absence of a portal forinfections (the feet, unlike the face, lack seba-ceous glands), a function of some as yet unrecog-nized unique anatomical feature of the feet, or thestandardized procedures among the practitionersinjecting. It may be because material injected intothe feet was limited to medical grade products freefrom contaminants. This last possibility is mostconsistent with the experience of physicians thathave safely and effectively used medical grade sil-icone for facial soft-tissue augmentation. Not onlyare silicone injections of the feet devoid of signif-icant complications but, according to Balkin, sil-icone has a near perfect record for relieving thepain associated with loss of the plantar fat pads.23

It also works very well for relief of painful corns.This near perfect clinical record of silicone

injections into the feet has been correlated his-topathologically. In one of the few long-term re-ports on the histopathology of liquid injected sil-icone, 148 specimens obtained from 49 patientswho had received injections into the plantar fatpad area were evaluated. Histopathologic evalua-tion revealed encapsulation without granulomaformation in these individuals.22 Podosil, a siliconeproduct, may be approved soon in Europe fortreatment of foot problems.

In contradistinction to its ethical usage, thecomplications arising from the psychopathic us-age are as sensational and outrageous as the meth-ods and materials used. Unfortunately for physi-cians and patients alike, the distinction betweenthese two methods of injection is lost by the mediaand legislators alike. The most common headlineone reads regarding silicone unquestionably re-fers to the outcomes of criminal misuse of agentsthat may not be silicone at all.

Several deaths have been reported as a resultof large-volume silicone injections performed byunlicensed personnel using impure products.These deaths were caused in most instances from

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industrial grade material injected in high volumesthat resulted in respiratory failure. Deaths in Flor-ida, California, and Texas have resulted in crim-inal prosecutions against the unlicensed person-nel that performed them. Less seriouscomplications from unlicensed usage of siliconeinclude infections with mycobacterium and gran-uloma formation.41,42

In addition, physicians injecting silicone mustbe able to tell those few patients who becomesilicone addicts to discontinue injections beforebecoming “potato heads” and must be capable ofrefusing treatment to those patients sufferingfrom body dysmorphic syndrome. All practitio-ners who use silicone will see patients who havebeen overinjected. In these patients, the physicianhas an ethical duty to refuse further treatment.

IMMUNOLOGYThe immunologic response to purified liquid

injectable silicone injected in minute quantities is,at the present time, unknown. It is know that allforeign bodies can elicit an immunologic reactionand that granulomas may be a generic response toforeign materials of all types.40 Although siliconesappear to be nonantigenic, they are not com-pletely biologically inert. Silicones undergo bio-logical oxidization to silica and, like tattoo pig-ments, are incorporated into the reticularendothelial system.1 It is anticipated that the useof molecular biologic techniques will facilitate anunderstanding of the roles of contaminants, vol-ume injected, and potential impact of infectiousand inflammatory processes on injected liquid sil-icone once it has been injected. To date, there hasbeen very little information about whether adverseevents associated with silicone are a result of anaberrant host response in a susceptible individual,an infection with an unusual response, or a normalhost response to a contaminant; in addition, thereare many other biologically important questions.The use of polymerase chain reaction, cytokineprofiles, and immunohistochemistry will mostlikely facilitate this understanding and, in turn,help us to understand what happens when thereis an adverse reaction to liquid injectable silicone.

The granulomas that occasionally form as areaction to silicone bear many similarities to cu-taneous sarcoid granulomas, and one potentialbenefit of an immunologic understanding of sil-icone granulomata is a molecular understandingof sarcoidal granulomas. It is interesting to notethat, as with sarcoidosis, silicone complicationsmay occur following “persistent exposure” to alow-potency antigen that initiates an inflammatory

cascade.42 Despite the fact that extensive clinicaltrials suggest that silicone is fundamentally safe,there has not yet been any application of thesemolecular biological techniques to elucidate howthe body reacts to this product.43,44

CONCLUSIONSTwo facts are certain about the future of liquid

injectable silicone for cosmetic soft-tissue augmen-tation. First, it will continue to be injected bothproperly and improperly. Second, the key to itssuccessful use will lie in an understanding of themicrodroplet technique, the use of a regulatedU.S. Food and Drug Administration–approvedproduct, and the avoidance and treatment of com-plications.

Future directions for treatments will includemolecules engineered to interact with an energysource (perhaps silicone embedded with a chro-mophore, which might allow a “permanent” fillerto be disassembled in the event of an untowardreaction or change of beauty ideals). Alternatively,better delineation of the immunology of siliconeinjections may permit the immune cells to scav-enge a bioengineered silicone molecule much thesame way that cutaneous dendritic cells and mac-rophages eradicate tattoo ink when stimulatedwith various energy sources. The single report ofAldara usage to treat silicone granuloma maypresage a day when toll-like receptors are manip-ulated to scavenge these granulomas and thoseassociated with sarcoid as well. Whatever the fu-ture holds for silicone injections, it is reasonableto assume that the injections will continue.

Rhoda S. Narins, M.D.Department of Dermatology

New York University Medical School2222 Westchester AvenueWhite Plains, N.Y. 10604

rsnmd@att.net

ACKNOWLEDGMENTThe authors thank David Duffy, M.D., clinical pro-

fessor of medicine, University of Southern California, formuch-appreciated consultations on the manuscript.

DISCLOSURESRhoda S. Narins, M.D., has no disclosures for sil-

icone. Disclosures for other fillers include being an in-vestigator and on the medical board of Q-Med and Medi-cis (Restylane) and Dermik (Sculptra) and being aninvestigator and on the medical board and owning stockoptions for ColBar LifeScience (Evolence), Bioform(Radiesse), and Artes (Artefill). Kenneth Beer, M.D., is

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a speaker for Medicis and conducts clinical trials forMedicis and Bioform.

REFERENCES1. Orentreich, D., and Jones, D. Liquid injectable silicone. In

Procedures in Cosmetic Dermatology: Soft Tissue Augmentation.New York: Elsevier, 2005. Pp. 77–91.

2. Duffy, D. Silicone granulomata management. Dermatol. TimesMay : 75, 2003.

3. Duffy, D. M. Silicone: A critical review. Adv. Dermatol. 5: 93,1990.

4. Duffy, D. M. Tissue injectable liquid silicone: New perspec-tives. In A. Klein (Ed.), Augmentation in Clinical Practice: Pro-cedures and Techniques. New York: Marcel Dekker, 1998. Pp.237–263.

5. Duffy, D. Liquid silicone for soft tissue augmentation.J. Dermatol. Surg. 31: 1530, 2005.

6. Duffy, D. Silicone conundrum: A battle of anecdotes. Der-matol. Surg. 28: 590, 2002.

7. Duffy, D. Presentation AS 352. Silicone granulomas: Causa-tion and treatment. Presented at the Annual Meeting of theAmerican Society of Dermatologic Surgeons, New Orleans,La., October 11, 2003.

8. Duffy, D. Complications of fillers: An overview. J. Dermatol.Surg. 31: 1626, 2005.

9. Orentreich, D. S., and Orentriech, N. Subcutaneous inci-sionless (subcision) surgery for the correction of depressedscars and wrinkles. Dermatol. Surg. 21: 543, 1995.

10. Orentreich, D. S., and Orentreich, N. O. Injectable Fluid Sil-icone: Principles of Dermatologic Surgery. New York: Marcel Dek-ker, 1989. Pp. 1349–1395.

11. Orentreich, N. O. Soft Tissue Augmentation with Medical-GradeFluid Silicone; Biomaterials in Reconstructive Surgery . St. Louis:Mosby, 1983. Pp. 859–881.

12. Orentreich, D. Liquid injectable silicone: Techniques for softtissue augementation. Clin. Plast. Surg. 27: 595, 2000.

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