All medical procedures carry some risk. However, soft tissue fillers are considered safe and effective. Besides an allergic reaction to the injected substance, side effects are few and typically due to the local injection itself. Still, individuals vary in their anatomy, their physical reactions, and their healing abilities. The outcome of treatment with Injectable is never wholly predictable. Risks unrelated to allergies include infection, abscesses, open sores, skin peeling, scarring, and lumpiness, which may persist over the treated area. We suggest that they are classified as early, late, and delayed. These time frames should be defined as less than 14 days, 14 days to 1 year, and more than one year, respectively. Early complications are considered inflammatory. Late complications are secondary to granuloma formation. Delayed complications may be due to biofilms.

Technical Aesthetic Complications

As with any complication in medicine, avoidance is far preferable to management. Fillers are classified by the US Food and Drug Administration (FDA) as devices, not medications. Therefore, the same precautions taken with other implantable devices apply with dermal fillers. However, the occurrence of post-treatment complications in some patients is inevitable. I can address the following difficulties efficiently if they result from reversible fillers:

Volume: too much or too little filler

Depth of treatment: filler injected too superficially or too deep.

Location: unfavorable anatomic location or asymmetry, or injection into the incorrect anatomical location.

I can quickly treat problems with reversible fillers such as Hyaluronic acid with Hyaluronidase to dissolve or remove undesired or insufficient volume may be addressed by adding more product. Still, I cannot easily remove irreversible fillers. Problems with irreversible filters are much more challenging to manage, especially if vital structures have been treated. Therefore, Prof. Moawad strongly recommends that they not be considered a first-line choice and should be used only by clinicians with substantial training and experience with these filler agents. Even in the best hands, complications may occur, which calls for extreme caution, especially when injecting the product around vital facial structures.

Swelling and Bruising

Swelling and bruising are both technique-dependent and patient-dependent variables that contribute to the degree of these expected side effects. I can minimize swelling and bruising by avoiding aspirin compounds, nonsteroidal anti-inflammatory drugs (NSAIDs), and many vitamin supplements for 7–10 days before the procedure. Swelling mediated by inflammatory cascade due to trauma or injection may also occur. Pre-treatment and post-treatment with ice can decrease the swelling and bruising response associated with cosmetic filler injection.

Lumps and Nodules

Lumps and nodules can be caused by almost any filler when too much is injected into a small area for various reasons, including incorrect dilution or reconstitution or inaccurate placement or technique. The resulting lump or nodule is usually easily treated with a simple incision and drainage using a sharp disposable needle. If nodules due to excess products are multiple or profound within vital anatomic structures, a formal incision and drainage may not be feasible. In such cases, HA products can be treated with HYAL. Capsular contracture around tissue fillers is quite rare. A small amount of local anesthesia may be needed to pass a larger bore needle or 16-gauge Luer-Lok syringe to break through the capsule and aspirate the material within. Hyaluronidase may be administered to clean up whatever remains behind. Hyaluronidase should be used with caution if an infection is suspected since this may spread the infection to surrounding areas.

Tyndall Effect

The Tyndall effect (bluish discoloration) results from the injection of HA fillers too close to the skin’s surface. It can readily treat bluish discoloration with HYAL.

Around the Eyes Filler Injection Complications

As filling the infraorbital region has become more popular, side effects, such as the appearance of eye bags, worsening of existing eyebags, or persistent upper cheek swelling, occur more frequently. This may occur when the injector treats too high, operates too close to the infraorbital rim, injects too deep, accidentally penetrates the septum, or injects too much product. Careful injection of HYAL into the area and subsequent massage to diffuse the HYAL and bring it into contact with the injected filler. Those injected with Radiesse; may be treated with injections of sterile water or saline (with or without lidocaine for local anesthesia) along with massage to help dilute the material mechanically. It is also important to remember that particulate forms of HA derivatives (such as the Restylane family of products) respond faster than the monophasic types (such as Juvéderm).

Persistent skin redness and Spider Veins

Persistent redness and spider veins that continue beyond two weeks after the injection may occur with any of the dermal fillers. Redness and spider veins after filler injection have also been treated successfully using Lasers or light.

Angry red bumps (granulomas)

Not red bumps that develop after injection immediately occur because of the uneven distribution of the product. Foreign body granulomas are the body’s attempt to remove foreign material. Therefore, granuloma formation can occur with any of the injectable dermal fillers. Nodule formation tends to occur as a delayed adverse reaction from the implantation of a filler. In an exact granulomatous process, all sites initially injected with filler material appear adversely affected at the same time. Infection may present clinically as single or multiple nodules, often with associated signs of inflammation, such as redness and pain. In addition, nodules secondary to a hypersensitivity reaction can present identically to those due to infection. They should be treated as infectious until a diagnosis of hypersensitivity has been established through thorough skin testing. The treatment of granulomatous inflammation should begin with an investigation of what agents have been injected. From there, the physician must decide the best pathway to success. Unfortunately, removing the product that has been diffusely injected into vital structures such as the lips is neither practical nor desirable. The options, then, consist of methods to control the inflammation and halt the process.

Once the diagnosis of granulomatous inflammation has been made because of treatment history, physical and, if possible, tissue biopsy, options for treatment are serial injection with cortisone or trials with various drugs. Prof. Moawad has found some success in the treatment of these lesions with graduated injections of triamcinolone acetonide. He starts with doses of 0.1 mL of a 10-mg/mL solution and then increasing the concentration to 20 mg/mL and 40 mg/mL with repeated injections until valid. Treatment should occur approximately every four weeks, and the amount injected should be carefully controlled to prevent post-treatment soft tissue atrophy. Prednisone in doses up to 60 mg/day has improved some patient signs and symptoms. Another approach is to discourage unusual cell growth by injection of 5-fluorouracil plus corticosteroids. For well-circumscribed nodular granulomas, surgical excision is the most effective and definitive approach.

Necrosis

The death of most or all the cells in the injection site (necrosis)due to injection is a rare but potentially overwhelming severe side effect with soft tissue fillers. Decay typically occurs due to either interruption of vascular supply due to compression or natural obstruction of vessels by direct injection of the material into a vessel. The glabellar region carries the highest risk of necrosis, presumably because of the small-caliber vessels supplying this region. An additional risk from intravascular injection in the glabellar area is blindness. This catastrophic complication occurs from the injected filler flowing in a backward fashion to the retinal artery. An increased risk of this event arises when a large volume bolus is inserted, such as greater than 0.1 mL of material. Of all the dermal fillers, PMMA carries the most significant risk of this complication.

I should take several precautions to avoid necrosis. These precautions include knowing the anatomy of the vasculature in the injection area, aspirating before injection, not using an excessive volume of the product, and not using extreme pressure during the injection. If necrosis is suspected, treatment options include applying warm clothes to facilitate local vasodilation, together with and the application of nitroglycerin paste – at the first sign of blanching – to promote further vasodilation. For cases in which an HA filler was employed, there has been a report of impending necrosis being successfully treated after injection of Hyaluronidase along with the distribution of the underlying vessel and adjacent violaceous skin. In this case, it is thought that the Hyaluronidase removed some of the products and decompressed the vessel. Therefore, it is recommended to inject the affected area with Hyaluronidase if an intravascular injection is suspected, with 75–100 units of the product. There is some evidence to suggest that using Hyaluronidase for impending necrosis, even if the dermal filler used was not an HA. The theory in this context is that the Hyaluronidase may also disperse the other material, allowing for revascularization. For severe or unresponsive cases of necrosis, deep subcutaneous injections of low-molecular-weight heparin into the affected area may be of benefit. Gentle wound care and application of ointment to the necrotic skin are also recommended. In cases of tissue loss, no reconstruction should be employed for several months, or at least until the eschar has fallen off and healthy circulation and tissue integrity have been restored.

Infection

Several infectious disease concerns have been associated with soft tissue fillers. It may be caused by bacterial, viral, and Candida species, and it may sometimes occur as a polymicrobial infection. The most common viral infection to occur in the skin after injection is herpes simplex. Patients with a strong history of cold sores or fever blisters may be pretreated with acyclovir, famciclovir, or valacyclovir to reduce the severity and duration of cutaneous herpes infections. If there is any question of ocular infection, consultation with an ophthalmologist is recommended since it may require surgical debridement of the cornea. Patients should be initiated on broad-spectrum antibiotics, such as a tetracycline plus a macrolide, to limit the emergence of resistant bacteria. Other antibiotic regimens include clarithromycin, quinolone, and minocycline, often for 4–6 weeks to cover for atypical mycobacterial infection, which may not grow well in culture. Reevaluation of the site should occur after 48 hours of antibiotic therapy, and if the fluctuance continues, incision and drainage and repeat culture should be sent. If no response to treatment occurs over several days, I should consider a biopsy for tissue culture and an adjustment of antibiotics. When there are multiple inflamed swellings, mainly in various sites corresponding to the injection sites, contaminated products should be suspected. The recommended management is the same as employed for single inflamed swellings, including incision and drainage, culture, and empiric antibiotics.

Biofilm

Some bacteria secrete a self-made, highly protective “slime layer”—or biofilm that acts as a form of a shell, blocking out the local environment to the point that antimicrobial drugs are no longer valid. Once a biofilm has developed, the bacteria have a “safe room,” and neither the immune system nor drugs or medication can penetrate the protective layer. Thus, bacteria can lie dormant for exceptionally long periods, only to reawaken and cause more problems once the environment is favorable again. As a result, when they arise from their planktonic state, they can cause angry bumps, boils, lumps, and even full-blown recurrent infection. These may be present on dental plaques, making the intraoral injection of soft tissue filler carrying a higher risk of secondary infection from these highly antibiotic-resistant bacteria. A further risk occurs when injection occurs soon after a dental procedure, which may disrupt the biofilm and increase the number of circulating bacteria. Any implant, including all fillers, significantly reduces the threshold at which contaminating bacteria can cause infection.

Furthermore, the punctures of repeated injections may reactivate inflammation. Until the foreign body is completely removed, it is difficult, if not impossible, to remove the biofilm; the bacteria are irreversibly bound to the foreign material. With solid implants, such as hip or knee joint prostheses, it is impossible to clean the devices ex vivo thoroughly, and I must replace them. New strategies for addressing this issue in solid implants include drug-eluting implant coatings, and future permanent fillers may utilize this strategy. With permanent fillers (e.g., PMMA), excision may be the only recourse available. If permanent implants are used in vital structures like the lips or eyelids, clinical options are limited, and I must make difficult choices. The clinician should consider these issues carefully when selecting between permanent or long-lasting fillers in such critical structures. The simplicity of being able to remove HA fillers with HYAL is a considerable benefit. To optimally prevent injection site infection, recommendations are as follows: properly sterilize the treatment area with either alcohol or chlorhexidine, never inject over areas of active infection, such as acne, herpes simplex, or impetigo, avoid intraoral injection, avoid injecting over an existent implant, and avoid injecting in patients who have undergone a recent dental procedure. To date, there is no proof that a simple alcohol swab prep and the use of non-sterile gloves are insufficient in preventing granulomas or filler infections. Still, Prof. Moawad believes that transferring surgical expertise in sterile technique to the clinic treatment room may further reduce the prevalence of these complications.

What is Hyaluronidase (HYAL)? What is Used For?

In the uncommon circumstance when an undesirable outcome occurs with hyaluronic acid, correction is possible with the injection of commercially available Hyaluronidase, which breaks down the unwanted hyaluronic acid dermal filler. Clinicians are encouraged to have it readily available to treat asymmetry or unfavorable cosmetic outcomes after HA injection, especially in emergencies such as impending necrosis due to vascular compromise. The use of Hyaluronidase for this purpose is not FDA approved and is considered off-label use. In many cases, 10- 30 units of unpreserved Hyaluronidase is enough to achieve the desired correction. I can perform additional corrections, although full correction may take up to 4 weeks to fully appreciate. It may be injected directly and slowly into the affected site to initiate hydrolysis of the previously injected HA. Injecting a small amount of appropriate local anesthesia will facilitate massage, essential in obtaining the therapeutic effect. The nature and quality of the dermal HA filler product are essential considerations for the effectiveness of HYAL. For example, the non-cross-linked HA fraction responds immediately (in seconds to minutes) to HYAL, allowing it to surround the tiny particles. Suppose a particulate form of dermal filler is used like Restylane. In that case, HYAL can quickly surround the granules of heavily crosslinked HA and hydrolyze the material over a broad surface area, several orders of magnitude larger than that of monophasic products like Juvéderm. With the Juvéderm family of products, HYAL can only affect the outermost surface of the aliquot, taking far longer to break down the HA. In Prof Moawad’s opinion, massage is essential to mechanically mix the HYAL with the HA and promote hydrolysis in the clinical setting.

Complementary Procedures to Filler Injections

Various techniques have been used to improve cutaneous changes seen with photo-aging to complement the effects of filler injection. Topical applications of tretinoin and alpha-hydroxy acids lead to increased collagen and diminished wrinkles. Increased deposition of new collagen has been reported after CO2 laser resurfacing, dermabrasion, and chemical peels. In recent years, wounding and new collagen deposition have been shown by the non-ablative skin resurfacing. Laser, light, and other energy-based technology such as radiofrequency or ultrasound treat skin wrinkling and sagging in a so-called non-ablative manner. In non-ablative tissue tightening, the epidermal injury is minimized, and thermal energy is directed into the reticular dermis and subcutis, where immediate tissue contraction and delayed remodeling cause skin tightening collectively. The attractive features of non-ablative skin tightening are limited post-procedure healing time, ability to return to work or social engagements, reduced risk of adverse events compared with ablative resurfacing or facelift, and less need for physician oversight. With careful assessment, appropriate intervention can be identified and employed to correct the inevitable effects of aging on appearance. Filler injection is an excellent medium for targeting individual areas for improvement, but adjunctive treatments can be of great utility when treating the entire face.

Platelet-rich plasma (PRP)

Platelet-rich plasma (PRP) is an autologous concentration of human platelets in a small volume of plasma. Many alternative terms to PRP are used in the literature, including autologous platelet gel, plasma-rich growth factors, and autologous platelet concentrate. The use of growth factors permeates many fields of medicine and surgery, including facial rejuvenation and plastic surgery, maxillofacial surgery, dentistry, oral surgery, tissue engineering, research and development, cardiovascular surgery, orthopedic surgery, and sports medicine, gastroenterology, and urology. Platelet preparations have applications in operation and are especially useful for the bony reconstructions met in facial plastic and reconstructive surgery. Their use in these situations has been associated with decreased operative time, the need for drains and pressure dressings, and the incidence of complications. Platelet-rich plasma has been applied to wounds, supplying hemostasis, adhesion, and enhanced wound healing—possible recent use for improving wound healing after ablative fractional CO2 laser resurfacing. Concentrated platelets are a rich source of seven fundamental protein growth factors actively secreted by platelets during the initiation of wound healing. Human growth factors have been investigated extensively, and clinical applications of individual growth factors such as keratinocyte growth factor and platelet-derived growth factors are used to treat oral mucositis and non-healing diabetic wounds, respectively. PRP production has been greatly simplified so that I can use it in the office and operating room.

Subcision Surgery

The term ‘‘subcision’’ denotes a method that involves cutting under a depressed scar, wrinkle, or contour using disposable needles inserted under the skin through a needle puncture. The procedure attempts to raise the base of the defect to the level of the surrounding skin surface. The integrity of the skin surface is minimally compromised, just as with a routine needle puncture. The effectiveness of subcision for correcting various types of skin depressions depends on two distinct phenomena. First, the act of surgically releasing the skin from its attachment to deeper tissues results in skin elevation. Second, the introduction of a controlled trauma initiates wound healing with consequent formation of connective tissue, resulting in augmentation of the depressing site.

Botox Injection

While technically not a filler, very tiny amounts of botox are injected into specific facial muscles to immobilize or relax the underlying cause of lines and wrinkles. It is commonly used to improve forehead creases, furrows between the eyebrows, and crow’s feet. Using botox and filler injection in the same area may achieve longer-lasting results. Prof. Moawad uses BTX-A routinely as adjunctive therapy with soft-tissue augmentation to make more effective, longer-lasting results, especially in some facial regions (i.e., deep glabellar furrows or lip augmentation).

New and Novel Filler Injections

Elastherapy

Elastin confers on tissue’s ability to stretch and recoil and plays a critical role in supporting and keeping healthy tissue. In the skin, most elastin is in the dermis. The more mature, thicker elastin fibers are found more in-depth in the dermis, where they function as an interpenetrating elastin network. A new approach to treat aged and damaged skin using elastin is currently in clinical development in Australia by Elastagen Pty Ltd. The method is unique to skin augmentation treatments. It is based on a recombinant human tropoelastin protein, identical to the one naturally occurring in healthy human skin. As seen in early clinical studies, this high degree of similarity to the natural elastin protein promises significantly higher tissue compatibility than achieved with animal-derived products or synthetic polymer materials treatment process, trademarked as definitive therapy. The treatment process trademarked as elastatherapy® also receives help from new formulation chemistry that enables the tropoelastin protein to be cross-linked with a low concentration HA part. There is no requirement for the toxic cross-linking agents often used in other products. The use of hyaluronidase to correct poor treatment outcomes is still a choice – a significant advantage over alternative filler materials. Elastin treatments benefit from the cell-supporting properties of elastin and the potential to stimulate skin cells, leading to the formation of new collagen at the treatment site. This latter property, coupled with the product’s smooth, cohesive structure, may present significant advantages over particulate products, which target collagen regeneration but carry a considerable risk of lumps and nodules. The product range also includes the potential to bulk the skin with a long-lasting, highly biocompatible elastin material and the unique prospect of restoring elastin to improve the skin’s physical properties and suppleness.

Latest

Laresse is a filler composed of carboxymethyl cellulose (CMC) and polyethylene oxide (PEO), described for augmentation. Laresse® was designed using measurements of the viscoelastic and physical properties of marketed filler injection composed of cross-linked HA. In a pilot study, 12 patients with moderate or severe nasolabial folds (NLF). All cosmetic injectable products are associated with the risk of both early and delayed complications. Early and expected side effects include swelling, bruising, and redness at the injection. It is of utmost importance that patients are educated on the treatment they consent to receive and the potential risk of these therapies. Side effects of the various cosmetic injectable products, including injectable neurotoxins and filler injections, are often technique associated, such as placing the filler injection too superficial or unintentional paralysis of facial muscles. Other complications, such as necrosis, intravascular injections, and infection, may not be entirely technique-dependent and must be managed swiftly and effectively. Finally, immunologic phenomena, such as delayed-type hypersensitivity reactions and foreign body granulomas, are complications that have no relationship to technique. Thus proper counseling and knowledge of management are needed. Loss of elasticity is one of the first signs of skin aging, followed by the appearance of visible wrinkles.

Hyaluronic acid (HA)-based filler injections are widely used to fill lines and compensate for volume loss. Recent clinical observations prove the persistence of the filling effect is longer than the biological availability of the filler injection. Stimulation of new collagen by cross-linked HA and up-regulation of elastin has been suggested to explain this observation and supported experimentally and cross-linked HA substitutes for fragmented collagen in restoring extracellular matrix required for regular activity of fibroblasts, such as collagen and elastin production. Several monthly sessions are needed. Boosting facial and non-facial skin through fibroblast activation is a new indication for HA-based products. Injectable HA has also been recently registered in Europe as an agent specific for improving skin quality (Restylane Skin boosters). Fat transfer, injectable filler injections, and alloplastic implants.

By understanding these issues, a surgeon can better discuss what would be ideal for a patient. Fat grafting offers the most cost-effective solution to a patient with enough volume loss. Injectable filler injections supply a natural, predictable, and correct non-surgical alternative that is scalable in cost. Alloplastic implants are ideally used in individuals with skeletal rather than soft-tissue deficiencies or in younger patients where the soft-tissue envelope is enough to mask the implant. The use of injectable products for cosmetic enhancement is increasing rapidly. This is mainly due to the full range of practical options, decrease in social stigma, and the excellent safety profile garnered by these products. However, complications do occur, and therefore, an awareness of the potential complications and how to best avoid or manage them will help maximize the success of these valuable therapeutic tools. The emerging objective of injectable treatment is facial harmonization rather than rejuvenation. Joint therapy is now a standard of care. Its use will increase further as we refine the concept that aspects of aging are intimately related and that successful treatment entails finding and addressing the primary causes of each.