Keywords
ComplicationsDermal fillerEcchymosisInjection site reactionsVascular compromiseTissue necrosisNodulesInfectionGranuloma formationEdemaHyaluronidaseHyaluronic acid18.1 Filler Complications
Adverse reactions from temporary dermal fillers are generally classified as early onset (up to 1 week after treatment) or late onset (weeks to years after treatment) where most delayed onset reactions are associated with the non-biodegradable fillers such as silicone, polyacrylamide, and polymethylmethacrylate (Carruthers and Carruthers 2013). Early onset adverse reactions typically include injection site reactions, nodules, Tyndall effect (hyaluronic acid fillers), infection, hypersensitivity, and vascular compromise leading to tissue necrosis (Carruthers and Carruthers 2013; DeLorenzi 2014). Late or delayed onset adverse reactions include infection, biofilm formation, and granuloma formation, however, any or all of these can occur in temporary or non-biodegradable filler types (Carruthers and Carruthers 2013).
18.2 Hyaluronidase
Dermal fillers are an integral part of aesthetic practice but on occasion, correction may be warranted. A benefit of using hyaluronic acid (HA) dermal fillers is they can be easily dissolved when necessary with an enzyme called hyaluronidase (Carruthers and Carruthers 2013; Casabona et al. 2018; DeLorenzi 2013). Because the HA fillers can be corrected easily with hyaluronidase, this makes it a popular option for tissue augmentation.
Certain circumstances in aesthetics, such as misplaced filler, vascular compromise, lumpiness, Tyndall effect, or unexpected outcomes, may require the use of a hyaluronidase solution (Carruthers and Carruthers 2013). Although hyaluronidase is an enzyme that dissolves HA dermal filler, it preserves endogenous hyaluronic acid. Even when large doses of hyaluronidase are used, the endogenous hyaluronidase returns to baseline after 48 h (Casabona et al. 2018). This suggests there is little reason to avoid its use when necessary, even in cases where some time has passed.
There are several different brands and viscosities of HA dermal filler and each respond differently to hyaluronidase according to the concentration or origin of the enzyme (ovine, bovine, or human recombinant) (Casabona et al. 2018). Three hyaluronidase products are available in the USA: Vitrase, Hylenex, and Hylase Dessau. There are two in Europe (Reductonidasa and Hylase Dessau); and one in Brazil (Hyaluronidase 2000). Hyaluronidase is an off-label option for correction of HA dermal filler placement although it is widely used in this capacity (Casabona et al. 2018). The particle size, cross-linking, and total hyaluronic concentration of the filler determine the viscosity and elasticity, therefore also determine the response from the hyaluronidase (Casabona et al. 2018).
Consequently, the breakdown of the filler occurs according to the thickness and stiffness or G-prime of the filler in relation to the type of hyaluronidase used (Allemann and Baumann 2008). Vitrase has been found to be the fastest hyaluronidase to dissolve HA fillers, however the speed of degradation slowed with higher molecular weights. Juvederm Voluma® was more difficult to break down and required more units and a longer amount of degradation time (Casabona et al. 2018; Flynn et al. 2013).
Most practitioners have found hyaluronidase completes its action of hydrolyzing the hyaluronic acid within about 2 min. It is recommended to use small amounts of hyaluronidase and possibly use a diluent of normal saline to control the concentration (Casabona et al. 2018). Depending on the reason and size of the area to be treated, the concentration and amount will vary. It is also important to understand the Restylane® family of products hydrolyze faster and easier than the Juvederm® family of products and should be dosed accordingly (Casabona et al. 2018; DeLorenzi 2013).
The practitioner should understand and the patient should be appropriately educated on the use and potential result of hyaluronidase used for dermal filler correction. For example, the enzyme can simply smooth out a lump, reverse an entire treatment in the case of unsightly results, or assist in the emergent treatment of vascular compromise, whichever is the case (Casabona et al. 2018). A consent form stating the side effects, risks, and benefits of hyaluronidase should be signed and the patient should understand the effect may reverse the original treatment attempt. A gradual hyaluronidase treatment regimen using small or diluted amounts over numerous appointments might help prevent reversal of the desired treatment while correcting the problem area (DeLorenzi 2013). Patients should be made aware that although the injection of hyaluronidase is not painful for most people, the solution may sting temporarily. In addition, because there is a small amount of solution in the area, temporary swelling may also occur, as well as bruising if a vessel is punctured. Warning the patient of this immediate and short-lived side effect will prepare them adequately and avoid reflexive reactions during and after treatment.
18.3 Injection Site Reactions
Injection site reactions with any dermal filler e.g., hyaluronic acid (HA), calcium hydroxyapatite (CaHA), or ploy-L-lactic acid (PLLA), are typically limited to bruising, redness, swelling, and/or tenderness (Carruthers and Carruthers 2013; Allergan 2013; Galderma 2016, 2018; Merz 2016). Discussion of these potential reactions with the patient prior to treatment is important because they can last up to 2 weeks. Good practice includes providing patients the option to re-schedule or postpone the treatment appropriately.
Patients would likely be upset if they had visible swelling, redness, or bruises in photographs or during a meeting and it is wise to help them avoid the embarrassment of having to explain these side effects. Advising the patient of these potential site reactions when the appointment is made allows the patient to manage the appointment and ensure scheduling is appropriate. This also allows the practitioner to avoid a last-minute re-scheduling issue.
Pre-treatment recommendations are appropriate to review with patients prior to their appointment to help them understand possible side effects (Carruthers and Carruthers 2013). In addition, post-treatment instructions are important to review with the patient before they leave the office to ensure they understand how to properly care for their skin and treatment area and also when to contact the office should any concerns arise (Carruthers and Carruthers 2013). The following is a sample of what can be suggested to patients prior to treatment, but individualized instructions are necessary for every patient.
Examples of Possible Pretreatment Suggestions (Table Not for Use in Clinics)
Avoid consumption of alcohol, taking blood thinning medications (check with the prescribing provider before stopping medications), high doses of Vitamin E, St. John’s Wort, and non-steroidal anti-inflammatory medications (i.e., Ibuprofen), for 7 days prior to treatment (Grunebaum 2018). Ingestion of any of these can increase bleeding time and the chance of bruising.
Homeopathic strength, low dose Arnica montana tablets may be taken as directed starting 3 days prior to treatment to help decrease the likelihood of bruising (Weinkle and Saco 2017). However, there is no guarantee that bruising and/or swelling will not occur. Therefore, it is highly recommended to schedule these treatments at least 2 weeks prior to a special event.
If a herpes simplex virus (HSV) labialis lesion or active infection is present in area of treatment, postponement of treatment is required until lesion/infection has resolved (Carruthers and Carruthers 2013; Cohen 2008).
Prophylactic treatment of HSV can be provided if appropriate (Carruthers and Carruthers 2013).
Immediately after the treatment, the most commonly reported side effects include temporary tenderness, bruising and/or swelling at the injection site. These effects typically resolve within several days with the majority of patients having complete resolution at or before 14 days (Casabona et al. 2018; DeLorenzi 2013). Post-treatment instructions for common site reactions are straightforward and can include the following:
Examples of Suggested Post-Treatment Recommendations (Table Not for Use in Clinics)
Swelling: Cold compresses may be used immediately after treatment to reduce swelling. Sleeping with the head elevated on pillows (head above heart) and/or an over- the-counter antihistamine for the first few nights post-treatment can help minimize swelling (Grunebaum 2018; Bray et al. 2010).
Bruising: Cold compresses may be used immediately after treatment up to 24 h post-treatment to reduce bruising. After 24 h post-treatment, warm compresses may be used to reduce bruising (Carruthers and Carruthers 2013; Grunebaum 2018).
Advise the patient to avoid touching the treated area within 6 h following the treatment. After that, the area can be gently cleansed with soap and water (Korting and Braun-Falco 1996).
Until the initial redness and swelling have resolved, advise the patient to avoid exposure of the treated area to intense heat and sun exposure to prevent increased erythema (sunlamp or sun bathing) (Narbutt et al. 2019).
If the patient is susceptible to herpes labialis, there is a risk that the needle puncture may contribute to a recurrence. Consider medications that may minimize a recurrence (Klein et al. 2019).
Advise the patient to avoid taking aspirin, non-steroidal anti-inflammatory medications, St. John’s Wort, high doses of vitamin E, and other blood-thinning supplements for 24 h after treatment. These agents may increase bruising and bleeding at the injection site (Carruthers and Carruthers 2013).
Advise the patient to avoid exercise and alcohol for 24–48 h post-treatment to help reduce incidence of edema (Urdiales-Galvez et al. 2017).
Advise the patient to avoid allowing pets to lick the face or treated area for 48 h post- treatment. The needle puncture creates a tunnel where bacteria might travel to deeper tissues if the site hasn’t completely healed.
Advise the patient a follow-up treatment before the product has fully dissipated might enhance the lasting effect.
18.4 Nodule Formation and Tyndall Effect
18.4.1 Nodule Formation
Nodule formation is an example of an unexpected complication from all temporary filler types because in some cases, the nodule can form long after the treatment has been completed. Nodule formation is an uncommon adverse event and is classified as early or late onset. Early onset nodules generally occur immediately or within days and are caused by too much product being placed in one area and/or product placed too superficially (Beleznay et al. 2015).
Early onset nodules from HA fillers can be easily corrected with hyaluronidase, incision and drainage, and/or massage. Some HA nodules spontaneously resolve (Carruthers and Carruthers 2013). In some cases, superficial nodules can be corrected using a sterile needle for incision and drainage by puncturing the superficial nodule and gently squeezing or massaging the product to remove it. When nodule formation occurs with HA filler, hyaluronidase may be used to dissolve the product, however it is important to understand that in cases where fillers other than HA are used, aspiration, surgery or other methods for removal of nodules may be warranted (DeLorenzi 2013; Beleznay et al. 2015).
Late onset nodules can occur days to years after treatment and, without biopsy, it is difficult to ascertain if they are inflammatory or infectious in nature (Beleznay et al. 2015). If the practitioner is unable to obtain a biopsy, it can be a challenge to treat the nodule effectively although hyaluronidase, antibiotics, and steroids have been used with success (DeLorenzi 2013). It is important to remember that hyaluronidase is effective only in dissolving HA products and it is not indicated for nodules of CaHA or PLLA.
Late onset nodule formation can also occur from biofilm formation (Beleznay et al. 2015). Biofilm is known as a subclinical infection produced by bacteria that was introduced during the initial procedure. The bacteria insidiously form a capsule that is very difficult for antibiotics to penetrate. However, biopsies have shown an inflammatory component in addition to the formation of biofilm formed by bacteria (Carruthers and Carruthers 2013).
Additionally, if too much dermal filler is deposited into a small area or if the filler is placed into the intradermal space rather than the subcutaneous layer, a late onset nodule can form. On occasion, the patient may not be able to see the nodule but the patient might be able to feel it when they touch the area and this may be troubling. For these reasons, it is crucial that clean and proper technique is used when replacing lost volume in the face (DeLorenzi 2013; Beleznay et al. 2015; Alam and Tung 2018).
18.4.2 Tyndall Effect
When clear gel fillers are placed too superficially in the dermis, the refraction of light of the gel and the melanin in the dermis display as a bluish discoloration of the skin. This is called the Tyndall effect. The Tyndall effect will persist over long periods of time, usually until the product is removed (Carruthers and Carruthers 2013; Alam and Tung 2018).
Recent advances in HA filler consistency and G-prime characteristics have provided practitioners with more choices to address different types of lines and wrinkles. For example, the thinner, lower G-prime fillers such as Restylane® Silk or Juvederm® Volbella are available tools for more superficial lines whereas the Restylane® Lyft or Juvederm® Voluma are better used in the deeper tissues of the mid-face (Allergan 2013, 2016a; Galderma 2017, 2018). These products have supplemented the aesthetic practitioner’s resources and provide wider options for correcting and smoothing various types of lines.
Some HA fillers with a lower G-prime are appropriate to place into the more superficial layers by experienced practitioners. The aim of superficial dermal filler placement is to correct pit-type scarring or superficial fine lines around the mouth or on other areas of the face that are caused from sun exposure (Allemann and Baumann 2008). Placing these lower G-prime or thinner fillers in the superficial dermal layers requires skill, and using small amounts of filler can avoid too much product being placed resulting in nodule formation or Tyndall effect.
18.5 Infection
Although infection is not common and there are no universal guidelines on skin preparation when injecting dermal fillers, precautions such as cleansing the skin with an antiseptic such as alcohol or chlorhexidine is recommended prior to treatment to minimize the risk. Chlorhexidine is a surgical preparation and can easily be utilized by aesthetic clinicians (Bailey et al. 2011). Chlorhexidine should be avoided around the eye area because of the potential for contact with the cornea leading to keratitis (Cohen 2008; Bailey et al. 2011). Sterile needles, gloves, and thorough handwashing are standard protocol when performing any injection to help avoid infection.
Infection etiologies include fungal, bacterial, or viral and may manifest within 2 weeks or up to 1 year after treatment (Carruthers and Carruthers 2013). Patients who have recurrent herpes simplex virus (HSV) eruptions may develop an outbreak as a result of treatment so prophylaxis is advised to prevent such an occurrence. On the other hand, if the patient has an active HSV outbreak with active lesions in the area of treatment, it is strongly recommended to avoid injections until after the area has cleared (Carruthers and Carruthers 2013; Klein et al. 2019).
All signs or symptoms of inflammation or infection demand the prompt notification and attention of a qualified practitioner. Depending on the etiology, infections can present as pustules, papules, vesicles, increasing redness, pain, and/or swelling and in some cases, the patient may complain of fever and fatigue (Grunebaum 2018; Chiang et al. 2017). Regardless of initial presentation, any papule or pustule of inflammatory nature must be treated empirically by an antibiotic until culture results, if appropriate, are returned (Carruthers and Carruthers 2013; Cohen 2008; Bailey et al. 2011). Treatment often requires prescription medications and may include antibiotics, antivirals, or antifungals, both topical and systemic, to ensure adequate coverage and prevention of spread of infection. The use of steroids as a first line treatment is not recommended due to the potential for worsening the infection (Habif 2016). Close observation and frequent follow-up of the patient is warranted until the signs and symptoms of the infection have completely resolved.
Unfortunately, there are reports of the use of counterfeit dermal filler products and these may contribute to an increase in infection rates so use of these products is discouraged (Carruthers and Carruthers 2013; Cohen 2008; Pickett and Mewies 2009). Patient safety and prevention of complications are priority but unfortunately, practitioners may unknowingly acquire counterfeit products. The purchase of aesthetic products and medications directly from the manufacturer is the preferred option for the prudent aesthetic practitioner.
18.6 Hypersensitivity and Granuloma Formation
Patients who have hypersensitivity reactions to any product, including dermal filler preparations, should be treated with extreme caution. In some instances, there may be no previous history of hypersensitivity reactions, but the patient may have a reaction after initial treatment with a filler (Carruthers and Carruthers 2013; Grunebaum 2018). Documented hypersensitivity reactions to HA fillers is extremely rare but it can occur, and the patient should be made aware of the potential risk (Carruthers and Carruthers 2013).
In some cases, the formation of a nodule is confused with granuloma formation. Nodules are described previously in this chapter. The formation of granulomas is an immune response (type IV hypersensitivity reaction) and is a systemic response where the tissue at every site of injection would react with the filler at the same time (Grunebaum 2018). Solitary nodule formation may have several different origins and other causes should be investigated. Granuloma formation should be histologically confirmed as foreign body granulomatous inflammation and treated appropriately by a qualified practitioner (Carruthers and Carruthers 2013; DeLorenzi 2013).
18.7 Vascular Compromise Leading to Tissue Necrosis
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