It can be painful if the procedure is carried out by injector who is not as skilled.
Generally, basic dermal filler procedures require no anaesthetic as the dermal filler contains local anaesthetic. It is simple and straight-forward, involving a few tiny injections directly into the skin, and takes between 15-30 minutes. Make-up can be applied immediately after the procedure and you can go straight back to work. Result can be seen immediately. Optimal results can be maintained over a long period of time through regular repeated treatments. The procedure varies from person to person depending on your requirements and the severity of the wrinkles that are being treated, in addition to the particular dermal filler being administered.
Dermal fillers in aesthetics: an overview of adverse events and treatment approaches. The ever-expanding range of dermal filler products for aesthetic soft tissue augmentation is of benefit for patients and physicians, but as indications and the number of procedures performed increase, the number of complications will likely also increase. Objective: To describe potential adverse events associated with dermal fillers and to provide structured and clear guidance on their treatment and avoidance.
Methods: Reports of dermal filler complications in the medical literature were reviewed and, based on the publications retrieved and the authors’ extensive experience, recommendations for avoiding and managing complications are provided.
Results: Different dermal fillers have widely varying properties, associated risks, and injection requirements. All dermal fillers have the potential to cause complications. Most are related to volume and technique, though some are associated with the material itself. The majority of adverse reactions are mild and transient, such as bruising and trauma-related edema. Serious adverse events are rare, and most are avoidable with proper planning and technique. Conclusion: For optimum outcomes, aesthetic physicians should have a detailed understanding of facial anatomy; the individual characteristics of available fillers; their indications, contraindi- cations, benefits, and drawbacks; and ways to prevent and avoid potential complications. Keywords: aesthetic medicine, complications
The popularity of dermal fillers has grown rapidly in recent years because they offer the rejuvenative and enhancing aesthetic improvements previously only achievable with surgery, but at lower cost and with limited-to-no recovery time. According to data from the American Society for Aesthetic Plastic Surgery (ASAPS), more than 1.6 million dermal filler treatments were performed in 2011, making them the second most popular nonsurgical cosmetic procedure performed in the USA after neuromodulators; the latter procedure is frequently performed in concert with dermal filler injections.1
As public awareness and acceptance of dermal fillers grows, so does the size of the market, with an estimated 160 products currently available worldwide from more than 50 companies. Their main indications are the filling of rhytides and folds, and correction of soft tissue loss due to disease or age.2 Increasingly, fillers are used for volume replace- ment and enhancement procedures,3 including cheek and chin augmentation, tear trough correction, nose reshaping, midfacial volumization, lip enhancement, hand rejuvenation, and the correction of facial asymmetry. As the indications and the number of procedures performed increase, the number of complications will likely also increase. Understanding the different characteristics, capabilities, injection techniques, risks, and limitations of available fillers is essential for injectors to reduce the risk of complications, improve patient outcomes, and care for patients who have experienced adverse events. This requires expert familiarity with the properties and potential complications of a wide range of products, including those that are not available in the injector’s country of practice, as patients may present with adverse reactions to fillers that were injected abroad. Particularly important is how the incidence of local adverse events following treatment is related to the injection tech- nique versus the chemical composition of the dermal filler.4 This review will provide physicians with a background to the etiology of filler-related complications, and structured and clear guidance on their treatment and avoidance.
Categories of dermal filler
Several methods of categorizing dermal fillers exist, but for a discussion of dermal filler complications it is perhaps most useful to categorize in terms of biodegradable (moderate and long duration) versus nonbiodegradable fillers, and in terms of particulate versus nonparticulate fillers (Table 1). Moderate duration biodegradable fillers, such as collagen and the hyaluronic acid (HA) fillers, are reabsorbed by the body quite quickly, so their cosmetic effects are relatively short-lived. HA derivatives are the most widely used biode- gradable fillers in both Europe and the USA,1,5 and generally have effects lasting 6–18 months depending on the source and extent of cross-linking and concentration and particle size of each product.6 HAs are linear polymeric dimers of N-acetyl glucosamine and glucuronic acid, which differ in the proprietary methods used to cross-link their dimers, their degree and method of chain cross-linking, the uniformity and size of their particles, and their concentration. These char- acteristics all have a significant impact on the clinical effect of these products. Increased cross-linking and concentration increase the viscosity and elasticity as well as the resistance to degradation by native hyaluronidase. The hydrophilic nature of HA means that the more concentrated and/or large particle products will tend to absorb more water, and thus produce more tissue swelling after injection. HA products are also characterized by the size of their microspheres. Biphasic fillers, such as Restylane®, Perlane®, and Macrolane® (all Q-MED, Uppsala, Sweden), contain a range of microsphere sizes. Monophasic HA products, such as Juvederm® (Aller- gan, Irvine, CA, USA), Belotero® (Merz Pharmaceuticals GmbH, Frankfurt, Germany), Teosyal® (Clarion Medical Technologies, Cambridge, ON, Canada), Prevelle Silk®
(Mentor Worldwide LLC, Santa Barbara, CA, USA), and VariodermTM (Adoderm, Langenfeld, Germany), contain homogeneous microspheres and are the preferred HA of most other companies. The different HAs have varying degrees of hardness (G’), which will influence their suitability for a particular procedure. In general, the greater the G’ of the product, the deeper it should be injected. It should be noted that while more concentrated products with a greater degree of cross-linking have a longer duration of effect, they also increase reactivity in the body and thus the risk of inflam- mation and granuloma formation.
Fillers with biodegradable particles that stimulate the body to produce its own collagen have a longer duration of effect; such products include calcium hydroxylapatite (CaHA; Radiesse®; Merz Pharmaceuticals GmbH) and poly-L-lactic acid (PLLA; Sculptra®; Valeant, West Laval, QC, Canada). CaHA consists of synthetic CaHA microspheres suspended in a carrier gel. Injection provides immediate visual improve- ment with long-term deposition of new collagen surrounding the microspheres, which contributes to an average duration of effect of around 15 months.7 PLLA is a synthetic polymer that provides soft tissue augmentation through stimulation of an inflammatory tissue response with subsequent collagen deposition.8 Each injection session with PLLA produces a gradual treatment effect and limited correction. Three injection sessions are generally required, but once the final correction is achieved, results last up to 2 years.
The nonbiodegradable fillers provoke a foreign body reaction that stimulates a fibroblastic deposition of collagen around the nonabsorbable microspheres.9 Products in this cat- egory include polymethylmethacrylate (PMMA; Artecoll®; Rofil Medical International B.V., Breda, the Netherlands), the polyacrylamide hydrogel Aquamid® (Contura International, Soeborg, Denmark), and Silikon® 1000 (Alcon Laboratories, Inc., Fort Worth, TX, USA), a medical-grade pure form of silicone. PMMA consists of 80% bovine dermal collagen plus 20% PMMA microspheres. The collagen vehicle is degraded within 1–3 months, leaving the microspheres encapsulated by a fine fibrous capsule. Aquamid® is a hydrophilic polyacryl- amide gel composed of 97.5% sterile water bound to 2.5% cross-linked acrylamide polymer. A continuous exchange of fluid occurs between the hydrogel and surrounding tissue, which becomes
Dermal fillers in aesthetics: adverse events and treatment approaches Table 1 Characteristics of commonly used fillers and their indications
Human collagen Purified bovine collagen with 0.3% lidocaine
Purified bovine collagen with 0.3% lidocaine
Creases, wrinkles, scars and lip enhancement; 100,000 particles per mL.
Smaller gel particle size (vs Restylane) used
to correct thin superficial lines; 500,000 particles per mL.
Deeper dermal filler with a larger gel particle size (compared to Restylane) used to fill deeper creases and more prominent facial lines;
10,000 particles per mL.
Medium-depth facial lines.
Contouring and volumizing facial wrinkles and folds. Juvederm Ultra 2 erases moderate lines (around lips, eyes). Juvederm Ultra 3 smooths wrinkles between nose and corner of mouth. Juvederm Ultra 4 is for severe folds and lines and for facial contouring. Juvederm Ultra XC is formulated with lidocaine. More highly cross-linked formulation for generalized facial volume enhancement and correcting deeper folds and wrinkles.
Very high viscosity gel for restoring lost facial volume; eg, in cheeks.
For fine superficial folds, including crow’s feet and perioral lines.
For moderate to deep folds and lip contouring. For deep folds and lip and volume augmentation.
Range of products for superficial lines to deep creases. Highly cross-linked.
For superficial wrinkles such as perioral lines and rhytides.
For moderate to deep wrinkles; for example, moderate nasolabial folds.
For moderate to deep wrinkles (eg, deep nasolabial folds).
For facial contouring (eg, cheeks and chin).
Teosyal® range consists of different formulations which restore face volume and repair cutaneous depressions.
Fine lines (around the nose, mouth, and frown area) and acne scars.
Deeper lines and furrows.
Zyderm 1 used for fine lines, wrinkles, and shallow scars.
Zyderm 2 used for moderate lines, wrinkles, and scars.
Deeper lines, wrinkles, and scars.
Duration of results
6 months on average, with retreatment every 6–9 months
Average treatment lasts about 4 months Lasts 1 year
Lasts up to 18 months
Lasts 12–18 months Lasts up to 12 months Lasts up to 12 months Lasts up to 12 months Lasts 6–16 months
Lasts 6–12 months Lasts 6–12 months Lasts 6–12 months Lasts 6–12 months Lasts 6–9 months
Lasts 3 months
Lasts 3 months Lasts 3 months
Lasts 3 months. The collagen fillers are not available in the United States
Fine lines/Restylane Touch
(2, 3, and 4) and Juvederm Ultra XC
Juvederm Ultra Plus and Juvederm Ultra Plus XC Juvederm voluma
Belotero Soft Belotero Basic Belotero Intense varioderm
Teosyal range (Deep Lines, Global Action, Ultra Deep, First Lines, Meso, Touch Up, Ultimate) Cosmoderm
Q-Med/Medicis Q-Med/Medicis Q-Med/Medicis
Genzyme/Inamed/ AllerganMentor Inamed/Allergan
Merz Pharmaceuticals Merz Pharmaceuticals Merz Pharmaceuticals Adoderm GmbH/ Medical Aesthetics group
Galderma Galderma Galderma
Inamed corporation Inamed corporation
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Funt and Pavicic
Table 1 (Continued)
Brand name Manufacturer Key component
Biodegradable collagen stimulator products
Duration of results
Lasts 1-2 years, effects develop gradually
At least 1 year; average 12–15 months
1 year, but may be permanent
At least 5 years
Calcium hydroxyl-lapatite microspheres suspended in a carrier gel
Contains PMMA enclosed in a solution of
3.5% collagen and 0.3% lidocaine 97.5% sterile water and
Addresses lines and wrinkles and adds volume. Moderate to severe facial folds and wrinkles.
Deeper wrinkles: collagen is absorbed, leaving PMMA to stimulate new collagen.
Facial volume restoration and contouring.
Abbreviations: HA, hyaluronic acid; PMMA, polymethylmethacrylate microspheres; vs, versus.
Dermal filler complications: avoidance and treatment
All dermal fillers have the potential to cause bruising (Figure 1). Bruising is observed more frequently after injec- tion into the dermal and immediate subdermal planes using fanning and threading techniques.11 Less bruising is seen when materials are injected using the depot technique at the preperiosteal level. Bruising is treated with cold compresses after the procedure and vitamin K cream.12 For persistent staining, treatment with pulsed dye light (Vbeam® ; Syneron Candela, Irvine, CA, USA) or potassium titanyl phosphate (KTP) lasers may be effective; the light emitted from these is more precisely absorbed by hemoglobin than other colors.
A number of steps can be taken to minimize bruising, including avoiding all blood-thinning medications starting 1 week prior to the procedure (aspirin, warfarin, dipyrida- mole, clopidogrel, nonsteroidal anti-inflammatory drugs [NSAIDs], fish oil, vitamin E supplements, St John’s Wort,
garlic tablets, gingko biloba, and ginseng).13 Patients should be advised to stay out of the sun as long as bruising persists, and vigorous exercise should be avoided for the first 24 hours to avoid raising blood pressure. Fillers that incorporate lido- caine and epinephrine (adrenaline) may reduce the amount of postinjection bruising; the former improves the comfort of injection while the latter inhibits activation of eosinophils that play a role in bruising and cause vasoconstriction as the procedure proceeds. The patient’s head should be elevated throughout the procedure and remain so for 24 hours. Bruising can be further limited by use of the smallest gauge needle that can deliver the filler, a slow injection technique with small aliquots of product, use of blunt cannulas,14 and limiting the number of transcutaneous puncture sites.
Short-term post-traumatic edema
Some transient swelling in the immediate postprocedural period is normal and occurs with all dermal fillers. This type of edema occurs very shortly after injection and is related to injection volume and technique. Treatment and avoidance is as for bruising. The majority of cases of postinjection, trauma-related edema dissipate within 1 week.
Antibody-mediated edema (angioedema)
Dermal fillers are essentially foreign bodies, and some patients may develop hypersensitivity to injected products due to an immunoglobulin E (IgE)-mediated immune response (Type I hypersensitivity reaction). This may occur after initial or repeated exposure. IgE stimulates
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Table 2 Types of dermal filler complication by onset of adverse
Dermal fillers in aesthetics: adverse events and treatment approaches
Figure 1 Bruising may be immediate or worsen over 3 days.
closely monitored to make sure the edema is not a result of
an infectious etiology. Rapidly progressing angioedema is treated as a medical emergency because of the risk of airway obstruction.
Chronic angioedema refers to episodes that last more than 6 weeks. These cases are often difficult to treat and have a variable response to medication. Table S1 highlights the treatment steps recommended. Each step is added to the previous one if an inadequate response is obtained. Edema should be controlled with the smallest dose of oral steroids that is effective. One of the authors (DF) has had success in reducing the steroid dose with concurrent use of the leukot- riene receptor antagonist montelukast (Singulair® 10 mg per day [Merck & Co., Inc., Whitehouse Station, NJ, USA]). This agent binds with high affinity and specificity to the cysteinyl leukotriene binding sites.
Nonantibody-mediated (delayed) edema
Delayed hypersensitivity reactions are characterized by induration, erythema, and edema, and are mediated by T lymphocytes rather than antibodies. They typically occur 1 day after injection, but may be seen as late as several weeks after injection and may persist for many months.16,17 Delayed hypersensitivity reactions are nonresponsive to antihistamines. The allergen should be removed (Table S1). In the case of HA, this will involve treatment with hyaluronidase. Other fillers may require treatment with steroids until the filler resorbs, laser treatment, and/or extrusion.18 Excision is a last resort.
Early events (occurring up to several days post-treatment)
Injection site reactions Erythema
edema Pain/tenderness Bruising
Acne papule formation Nodule/abscess
edema Pain/tenderness Nonfluctuant nodules
Lumps, asymmetries, contour irregularities caused by technique and placement errors
Redness Whiteness Hyperpigmentation
Local tissue necrosis caused by vascular occlusion
Delayed events (occurring from weeks to years post-treatment)
Infection (atypical; eg, mycobacterial) Erythema
Systemic responses to infection Biofilm
Foreign body granuloma
Varying from subclinical histologic changes to disfiguring nodules
Migration of implant material
Local and site of injection and generalized hyaluronidase treatment should be given to patients injected with HAs. The incidence of malar edema can be reduced by proper patient and filler selection, limiting filler volume, and by placing filler material deep to the malar septum at the immediate preperiosteal level.19 The authors strongly recom- mend the use of an HA when treating the infraorbital hollow so that hyaluronidase may be used to dissolve the material if adverse events occur. A filler of low elasticity and viscosity is preferred, as this limits lymphatic compression. In addi- tion, a filler may be placed at the immediate subcutaneous level superficial to the area prone to lymphatic obstruction. A material such as Belotero® Balance or Soft that does not cause a Tyndall effect when injected superficially should be used in small quantities. Superficial injection, if properly placed and limited in volume, should not result in malar edema. Persistent malar edema should be distinguished from overcorrection.
Immediately after injection, some skin redness is normal (Figure 5). If erythema persists for more than a few days, a hypersensitivity reaction is likely. Treatments for rosacea may be effective, including oral tetracycline or isotretinoin. A medium-strength topical steroid is advocated for persistent erythema. Long-term use of high-potency steroids should be avoided, as they may cause atrophy and telangiectasias. Lasers can be effective for the treatment of telangiectasias and erythema (for details of laser treatment, see Bruising section). Vitamin K cream is useful in accelerating resolu- tion of erythema in addition to facial bruising.22 Patients with rosacea have a higher risk of developing postinjection erythema and should be warned of this prior to beginning the procedure.
a bleaching agent such as topical hydroquinone (2%–8%) and Retin-A (tretinoin) combined with daily full-spectrum sunscreen application. Chemical peels may also be used to treat resistant postinflammatory hyperpigmentation. If unsuccessful, the next step is treatment with IPL, a pulsed dye laser or fractional laser; the low fluence Q-switched Nd:YAG 1,064 nm laser is also effective. Current lasers have limited use in the treatment of Fitzpatrick skin types IV–VI, but the long wavelength Nd:YAG laser allows darker skin to be treated without disrupting natural skin color, and IPL systems can treat Fitzpatrick skin types I–IV. Limiting the number of skin punctures during the injection process by using the linear threading or fanning technique or injecting at the preperiosteal level may reduce postinjection erythema and therefore postinflammatory hyperpigmentation.
When particulate HA fillers are inappropriately implanted into the superficial dermis or epidermis, a bluish hue may occur as a result of the Tyndall effect (scattering of light by particles in suspension). Blue light waves have a higher frequency than red and are more easily scattered, so that when a ray of light hits the skin’s surface, it is reflected in many different directions, with blue becoming the prominent color that emerges. This effect can occur with all particulate HA fillers, but does not appear to be caused by Belotero®, a monophasic polydensified nonparticulate gel.25 The more superficial the placement of material, the longer the duration of the discoloration. Hyaluronidase should be the initial approach to treatment. For HAs that are less susceptible to hyaluronidase because of a high degree of cross-linking or large particle size, multiple treatments may be necessary. As a last resort, dyspigmentation can be treated by nicking the skin with a small-gauge needle (30 gauge) or surgical scalpel (#11 blade) and expressing Abscess formation is a rare complication occurring any time from 1 week to several years after treatment; it may persist for weeks, and periodically recur for months. Abscesses should be treated with incision, drainage, and antibiotics. Cultures should be obtained. Treatment should then be tailored to the obtained sensitivity reports.28 Midfacial and periorbital infection can in rare cases result in intracerebral complications.
Dermal filler injections can lead to reactivation of herpes virus infections (Figure 7). If the treatment is targeting the lips or mouth area and the individual has a history of cold sores, prophylactic treatment with valaciclovir (500 mg twice daily [bid] for 3–5 days) can be started prior to injection to reduce the likelihood of this occurring. If the patient has not received prophylactic treatment, but infection is recognized early, valaciclovir at a dose of 2 g bid for 1 day should be given. If suprainfection occurs, the patient should be treated with appropriate antibiotics. The majority of herpetic recur- rences occur in the perioral area, nasal mucosa, and mucosa of the hard palate. Shingles after injection is very rare. When a blistering reaction occurs outside of the areas of recurrent herpes simplex virus infection (lip skin and vermillion, nasal mucosa, and mucosa of hard palate), vascular compromise should be seriously considered.
Figure 7 Dermal filler injection leading to herpes virus reactivation.
Clinical, Cosmetic and Investigational Dermatology 2013:6
Nodules are frequently observed after soft tissue augmentation. As they can arise from a number of causes, investigation may be required to establish a diagnosis. Visible material is more common in areas of thinner skin. Nodules must be categorized as inflammatory or noninflammatory.
When too much material accumulates in an area as a result of poor technique (overcorrection, too superficial placement of a filler, or use of a filler for an incorrect indication such as intramuscular placement in a sphincteric muscle; Fig- ure 8), a noninflammatory nodule may result that is palpable and may be visible. Such implant nodules form isolated lumps in the area of injection that do not grow, and which are well defined from the surrounding tissue. They appear early after the procedure and should be differentiated from foreign body granulomas, or biofilms, which are a result of an inflammatory reaction around the product or site of infection and occur later. Poor filler placement and the use of particulate fillers (eg, PMMA, CaHA) in highly mobile areas such as the lips can cause delayed-onset noninflam- matory nodules.29 Implant nodules are one of the most common adverse events following dermal filler procedures,33 but their inci- dence can be reduced by taking care to avoid too superfi- cial placement of filler, selecting the appropriate filler for the tissue site, massaging after injection to ensure even distribution and smoothness, and avoiding intramuscular injection.
Biofilms are widespread in nature and consist of densely packed communities of bacteria that surround themselves with secreted polymers. When a material is injected into the skin or subcutaneous tissue, it can become coated with bacteria and form a biofilm. These complex collections of bacteria secrete a protective and adhesive matrix that allows them to irreversibly adhere to a living structure or inert surface, where they give rise to a low-grade chronic infection that is resistant to antibiotics.34,35 A mature biofilm will release individual free-swimming bacteria in the tissues. Many bacterial species form biofilms, and as biofilms progress they become more antibiotic and culture resistant. When activated, for example by trauma from a further dermal filler procedure, the biofilm can cause a local infection, a systemic infection, or a granulomatous or inflammatory response.
Distinguishing inflammation due to a bacterial biofilm from a low-grade hypersensitivity reaction is difficult. Furthermore, these infections are difficult to treat, and so the focus should be on prevention. If a red, indurated area appears at any time after treatment, regardless of duration, a biofilm should be suspected.36,37 Persistent infla estylane®. Cosmetic Dermatol. 2007;20(12):784–786.
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20. Griepentrog GJ, Lucarelli MJ, Burkat CN, Lemke BN, Rose JG. Periorbital edema following hyaluronic acid gel injection: a retrospective review. Am J Cosmetic Surg. 2011;28(4):251–254.
21. Pessa JE, Garza JR. The malar septum: the anatomic basis of malar mounds and malar edema. Aesthet Surg J. 1997;17(1):11–17.
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Ice or cold compresses
Oral or injected antihistamines
Oral or intravenous corticosteroids
Oral corticosteroids and/ or immunosuppressants