An Introduction to Injectable Complications

By Catherine Fairris / 19 Apr 2018

Dr Catherine Fairris provides an introduction to the types of complications that may occur after toxin and filler injections

Minimally invasive aesthetic techniques such as botulinum toxin injections and dermal fillers are often seen as a safe and cost effective aesthetic option. If performed by experienced, well-trained practitioners, the probability of complications occurring is relatively small; however, there are complications that patients can experience.

This article will discuss the common complications that may occur as a result of botulinum toxin and dermal filler treatments and will briefly state the routine management approaches. As this article is an introduction, it will not go into significant detail, but instead hopes to educate practitioners who are new to aesthetics.


Botulinum toxin type A (BoNT-A) injections are the most commonly performed minimally invasive cosmetic procedure.1,2 BoNT-A acts by inhibiting the release of acetylcholine from presynaptic nerves at the neuromuscular junction, thereby hindering muscle contraction of both smooth and striated muscle.3 Although eight serotypes of BoNT exist, only type A is approved by the US Food and Drug Administration (FDA) for cosmetic use.1,3 BoNT-A-related adverse effects are relatively uncommon and the majority tend to be mild and temporary, usually occuring as a result of the effect of the product on unintended muscle groups after injecting.1

Adverse effects of BoNT-A

Adverse events caused by injection into unintended muscle groups or unexpected diffusion of product to surrounding muscle can lead to focal facial paralysis and muscle weakness, causing eyelid ptosis, diplopia and facial asymmetry.1,3,4 The risk of these adverse events can be reduced if the practitioner has a good understanding of patient anatomy, product dosage and dilution, and indication for treatment.1,3,4

A systematic review of 31 clinical studies (with a total of 1,678 participants) of botulinum toxin type A in aesthetic treatments found the incidence of eyelid ptosis (2.5 %), brow ptosis (3.1 %), eye sensory disorders (3%), and lip asymmetries and imbalances of the lower face (6.9%)5 to be relatively low. The most commonly reported toxin adverse effects are injection site pain,1 which can be reduced by reconstitution with 0.9% bacteriostatic saline.6 Other commonly reported complications of BoNT-A are injection site ecchymosis, headaches, and fever/ malaise.1,2,4 Bruising can be significantly reduced by careful assessment of injection sites and placing puncture sites away from superficial blood vessels,1,4,5 especially around the periorbital region, which has a rich vascular network. Pre-treatment with topical anaesthetics and using small gauge needles – such as 30-32G – can minimises pain, whilst ice packs can be useful to reduce swelling and bruising pre and post treatment.1 Patient avoidance of aspirin, non-steroidal anti-inflammatory drugs (NSAIDS) and vitamin E derivatives for seven days prior to treatment can also help to reduce bruising,1 although comorbidities must be taken into account when recommending this. For example, if the patient has cardiovascular risk factors and is taking prophylactic aspirin, it may not be safe to stop.

The occurrence of headaches following injection of BoNT-A has been widely researched. In a study of 264 patients treated with BoNT-A for glabella lines (203 in treatment arm and 61 placebo), 15.3% of the treatment group reported headache, which was the most frequently reported adverse effect.7 However, headache was also reported in 15% of the placebo group. Therefore, the authors concluded that it was likely related to the injection itself rather than the BoNT-A.7 Management is, as with other causes of headaches, conservative or with simple analgesia.4,5,7

Eyelid ptosis can occur if BoNT-A spreads to the levator palpebrae superioris muscle, usually as a result of downward diffusion of BoNT-A when attempting to treat glabellar and forehead rhytides.4 Ptosis can occur up to two weeks’ post treatment, and usually lasts between two to four weeks.4 The incidence is reported to be between 1-5% of glabellar and forehead treatments.4,5 To avoid this, injections should be placed at least 1cm above the brow and should not cross the mid-pupillary line laterally. If ptosis occurs, it can be treated with application of alpha- 2-adrenergic agonist eye drops to cause contraction of the Müller’s muscle, which elevate the upper eyelid.8 For example, two to three drops daily of apraclonidine 0.5% into the affected eye until symptoms resolve should be effective.2,8

When treating the periocular region, there is a risk of diplopia and loss of voluntary eye closure, which can be avoided by injecting BoNT-A laterally to the orbital rim, placing injections superficially within the orbicularis oculi muscle and by injecting small doses.

Dermal fillers

There are currently more than 100 dermal filler products available in the European market.9 They can be broadly divided into their duration of action, temporary or permanent.10 Temporary fillers are biodegradable with effects lasting between three to 24 months. Temporary dermal fillers are: hyaluronic acid (HA), poly-l-lactic acid (PLLA), calcium hydroxylapatite (CaHA), and collagen, which is not as common.9,10 Dermal fillers such as polymethyl-methacrylate (PMMA) and silicone, are considered permanent as they cannot be absorbed and broken down by the human body.9

Dermal filler use in aesthetic medicine is broad; from addressing fine lines and wrinkles to facial contouring and projection.7,10 The choice of filler is often based on the anatomical area that needs to be treated, the volume that is required to reach the best aesthetic result, longevity of the product and the cost.10

The most popular type of dermal filler is hyaluronic acid (HA), which generally has the best safety profile amongst all non-autologous dermal fillers.10 This is because HA is a naturally occurring molecule that is identical across species, therefore HA fillers are minimally immunogenic and easily dissolved by the enzyme hyaluronidase.11,12 HA molecules are linear polysaccharides which are negatively charged to bind water. Chemical cross-linking stabilises them, although they are broken down gradually, so they are not permanent. The more cross-linking they contain, the longer it takes to break them down.10

Although the injection of dermal filler is described as minimally invasive, related adverse effects may be more serious, with greater long term sequelae, for example vascular occlusion.10 Injection site reactions tend to be the most common complication reported due to immediate trauma to the skin from the process of injection, irrespective of the type of dermal filler used.10 Complications can be classified as minor and short lived; such as swelling, redness, tenderness, and bruising which tend to last between four to seven days,11 to delayed complications occurring months or even years later, for example, granuloma formation – discussed below.10 Complications of dermal fillers can be broadly divided into technical errors (injection of an inappropriate volume of filler, inaccurate depth of filler injection, injecting in the wrong location and inappropriate filler choice) and inflammatory complications (contamination by infectious agents and immune-mediated reactions).11

When HA complications occur, the fillers can be broken down by hyaluronidase, which is a mucolytic enzyme that hydrolyses the HA in both natural and cross-linked form.11,12 An example of this is if the filler has been injected too superficially, as superficial placement will cause a bluish discolouration of the skin overlying the filler (the Tyndall effect), which does not resolve until the filler has been removed or has been resorbed.9,10,13

As with BoNT-A, injection site pain can be minimised by using topical anaesthetics, by injecting local anaesthetic such as lidocaine (if the dermal filler being used does not already contain lidocaine), or by using topical gel packs before and after treatment.9,13 The practitioner’s injection technique can also influence whether the patient develops bruising and swelling. For example, rapid injection of filler, the use of the fanning technique, as well as using large volumes of filler, have all been shown to increase the incidence of bruising, and swelling.4,9,13 These complications can be minimised by using blunt tip cannulas, small gauge needles (as appropriate to the viscosity of the product) and limiting delivery to the smallest volume of filler required to achieve the best aesthetic result.4,9,10,11,13

Adverse effects of dermal fillers

Hypersensitivity reactions

Hypersensitivity reactions – the development of swelling, erythema, and tenderness within a few minutes of dermal filler injections – have also been reported. In 2002, a review article by Friedman et al. stated that the incidence of hypersensitivity reactions reported with HA fillers in the year 2000, was 0.02%.1 The risk of hypersensitivity is thought to be greatest in dermal fillers that contain bovine collagen, however it is a theoretical risk with all types of dermal filler. Therefore, skin testing is recommended in patients with a history of anaphylaxis or allergy to any of the constituents of the filler, for example, lidocaine. Skin testing prior to use of polymethylmethacrylate (PMMA) filler is mandatory as it contains bovine collagen making it highly immunogenic.1,9,13


Granuloma formation can occur with any injectable filler. Subclinical granulomatous inflammation is a normal tissue response to the injected material; therefore, it is the degree and severity of granuloma that determines significance.11,14 Granuloma formation is the body’s attempt at removing foreign material. Histologically, they contain inflammatory infiltrate composed of histiocytes and epithelioid cells.14 They are separate from nodules which are isolated single ‘lumps’ of product surrounded by a fibrous capsule, becoming palpable within weeks of treatment.14

Granuloma formation is usually a late complication of filler injection. The risk of granuloma formation is less with resorbable fillers, compared with permanent fillers. Administration of local or systemic steroids can be used as treatment; 5-fluorouracil can be injected into the lesions to reduce growth. Surgical excision is recommended for larger, well-defined lesions.9,10,11,13,14 

Vascular occlusions

The most serious complication of dermal fillers are vascular complications, which are also known as embolia cutis medicamentosa (ECM) or Nicolau syndrome.12 Vascular events usually occur as a result of accidental intravascular injection of dermal filler into an artery, thus leading to obstruction of blood supply to distal tissues.6,9,12 Obstruction of blood supply can cause blindness; for example, inadvertent bolus injection into the angular artery has the potential to cause blindness via retrograde flow of filler into the ophthalmic artery.12

Management of artery occlusion is very difficult, therefore the best method is avoidance. Careful assessment of the patient is strongly advocated and if there is any doubt as to whether an artery is close to the site of injection, then the injection of a small amount of adrenaline into the proposed treatment area can be used to identify and constrict arteries.12

Cannula use has also been shown to reduce the risk of vascular occlusion4 and avoiding small bore needles can reduce the likelihood of the needle entering the lumen of the vessel to deposit filler intravascularly. Although, larger bore needles are more likely to cause bruising.10,12,13 Injecting slowly and using small bolus of product (0.1ml or less) at a time can also reduce the risk of depositing large volumes of product intravascularly.12 If vascular occlusion occurs, having a clear protocol of how to manage the situation to minimise morbidity is extremely important. The protocol for management is too vast to detail in this article, but it is vital that practitioners can identify the signs and symptom associated. Initially there may be severe pain, blanching of the skin distal to the site of occlusion and livedo reticularis.10,12 However, symptoms may take several hours to present or evolve over a period of a few days, so patients should also be advised to be aware of pain disproportionate to the treatment received, persisting for longer than expected, change in skin colour, and exudate.10,12


Biofilms are a living bacterial colony that adhere to a foreign implant and encapsulate it.15 Biofilms evade the host immune system by altering gene expression. They are characterised by recurrence and chronicity. Definitive treatment usually only occurs following removal of the implant as biofilms are notoriously difficult to treat.15


Preparing for filler emergencies is paramount, and literature has advocated that injectors have access to a ‘filler crash kit’, which includes hyaluronidase, aspirin and topical nitroglycerin paste. This can be used in the event of vascular occlusion (Figure 3).12

After treatment, close monitoring of the patient should take place and referral should be made, without delay, to a hospital for urgent vascular surgeon input.12


Severe adverse reactions to BoNT-A are rare and most complications are usually reversible. Complications of dermal fillers can cause significant morbidity and mortality, and aesthetic practitioners need to have a very good understanding of the anatomy and the products they are using. Preparedness with a ‘filler crash kit’ and vigilance of the development of complications will ultimately ensure that treatment is started promptly, which should improve outcome. Practitioners should ensure they are adequately trained before attempting any BoNT-A or dermal filler treatments. 


1. Cox S.E. and Adigun C.G. Complications of injectable fillers and neurotoxins. Dermatologic Therapy. Vol 24, 2011, 524-536

2. Cosmetic surgery national data bank statistics. Aesthetic Surg. J. 2016;36(1); pp1-29 https://academic-oup-com.ezproxy.library.

3. Botox®Insert: cosmetic_pi.pdf

4. Christiansen D. and Stebbins W. A Guide to Safety in Dermatologic Cosmetic Procedures: Avoidance and management of common Pitfalls and Perils. Curr Derm Rep (2013) 2:125-134

5. Brin MF, Boodhoo TI, Pogoda JM, et al. Safety and tolerability of onabotulinumtoxinA in the treatment of facial lines: A meta-analysis of individual patient data from global clinical registration studies in 1678 participants. J Am Acad Dermatol. 2009;61:961. e1–970.e1.

6. Alam M, Dover JS, Arndt KA. Pain associated with injection of botulinum A exotoxin reconstituted using isotonic sodium chloride with and without preservative: A double-blind, randomized controlled trial. Arch Dermatol. 2002;138:510–514.

7. Carruthers JV, Lowe NJ, Menter MA A multicentre, double blind, randomized, placebo-controlled study of the efficacy and safety of botulinum toxin type Ain the treatment of glabella lines. J AM Acad Dermatol. 2002; 46: 840-9

8. Omoigui S and Irene S. Treatment of Ptosis as a complication of Botulinum Toxin Injection. American Academy of Pain Medicine. 2005; 6(2); 149-151

9. Wollina U., Goldman A. Hyaluronic acid dermal fillers: safety and efficacy for the treatment of wrinkles, aging skin, body sculpting and medical conditions. Clin Med Rev Therapeutics 2011; 3:107-121

10. Luebberding S. Alexiades-Armenakas M. critical Appraisal of the Safety of Dermal Fillers: A primer for Clinicians. Curr Derm Rep (2013) 2:150-157

11. DeLorenzi C. Complications of Injectable Fillers, Part 1. Aesthetic Surgery Journal (2013), Vol. 33(4) 561-575

12. DeLorenzi C. Complications of Injectable Fillers, Part 2: Vascular Complications. Aesthetic Surgery Journal (2014), Vol. 34(4) 584-600

13. Christiansen D., Stebbins W. A Guide to Safety in Dermatologic Cosmetic procedure: avoidance and management of common pitfalls and perils. Current Dermatology Reports. 2013 2(2) pp125-134

14. Foreign Body granulomas after all injectable dermal fillers: Part 1. Possible causes. Plastic and Reconstructive Surgery Vol 123(6), 2009 pp1842-1863

15. Daines SM and Williams EF. Complications Associated with Injectable soft-tissue fillers. A 5-Year Retrospective Review. JAMA Facial Plastic Surg. 2013;15(3): 226-231 


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