CPD: Avoiding Toxin Complications

Avoiding Botulinum Toxin Complications

Oral surgeon Mr Sami Stagnell and maxillofacial surgeon Ms Natasha Berridge present an overview of the common complications of botulinum toxin by anatomical region and how to avoid them

In recent years, practitioners’ awareness regarding the potential complications of injectable treatments has vastly improved. The growth of groups such as the International Association for Prevention of Complications in Aesthetic Medicine (IAPCAM) and the Aesthetics Complications Expert (ACE) Group, as well as the rise of selfregulation, are a snowballing form of justice within the industry that strives to establish its credibility. Following the parliamentary debate led by conservative MP Alberto Costo earlier this year, the Government has reiterated that it will continue to explore options to strengthen the regulation of nonsurgical cosmetic procedures and enhance patient safety through more streamlined training of practitioners.1 In fact, in May 2019 the Department of Health and Social Care launched a patient safety consumer campaign to help spread the word of the dangers behind surgical and non-surgical aesthetic treatments.2 Undeniably, there are now greater numbers of patients seeking cosmetic treatments to enhance their natural visage, fuelled by reality TV personalities and social media icons alike.3,4 Patients are often unaware of the associated serious risks that could occur if treatments are not performed correctly. Fundamentally, it is crucial that medical aesthetic practitioners maintain a diligent, standardised approach to patient selection and assessment. Furthermore, with the majority of practitioners engaging with the continuous learning required to develop as a trustworthy provider, it is imperative that the profession remains abreast of managing and dealing with complications. This article is not an instructional guide for complication prevention and management, but aims to raise awareness of how to minimise the incidence of botulinum toxin type A (BoNT-A) complications based upon the following facial aesthetic zones: upper face, mid-face and lower face and neck.

Consultation Contraindications to BoNT-A treatment should be identified in the patient assessment: this includes infection at injection site, known hypersensitivity, as well as patients taking aminoglycosides and skeletal muscle relaxants as it may potentiate the effects of these drugs. However, in our experience, the injector is unlikely to come across these medications in routine practice. BoNT-A should be used with caution in patients with a history of neuromuscular disease e.g. myasthenia gravis.5,6 As part of the comprehensive patient assessment, careful evaluation of the underlying musculature, blood vessels and associated nerves are vital to optimising a successful aesthetic outcome. Furthermore, the treating clinician must have an appreciation of the individual patient’s own muscle activity and determine if any pre-existing asymmetry exists and its cause;7 it is not unusual for BoNT-A to be used in the management of facial asymmetry following medical issues such as facial palsy.8

General risks of BoNT-A and avoidance As with all injectables, there are risks associated with treatment, which might present simply as a side effect of treatment itself without being attributed to a specific causative factor; this includes an inability to meet patient expectations or undesired over/undertreatment of muscle groups.7,9 A retrospective review of a database endorsed by the American Society of Plastic Surgeons between 2008-2013 reported that despite a greater uptake of aesthetic facial procedures, when compared to younger patients, older patients (over 65) had a complication rate that was statistically insignificant despite confounding factors such as raised BMI, diabetes mellitus or health risks in the older age group.10 Fortunately, adverse events secondary to BoNT-A have been reported to be relatively uncommon and the majority tend to be mild and temporary; these include ecchymosis, flu-like illness, local injection site pain and erythema. Mild adverse events tend to occur in approximately 3% of patients.11,12 Most occur if the toxin is inadvertently injected into unintended muscle groups or erroneously diffuses into muscles in the surrounding region.13 More commonly occurring risks include pain, bleeding/bruising and headache.14 We recommend the use of pre-treatment application of ice and a local anaesthetic cream such as EMLA, avoid the repeated use of a blunted needle (risk when injecting with insulin syringes) and reconstituting BoNT-A with preserved normal saline to minimise the perception of pain.14,15 Good lighting and a proper injection technique will allow the practitioner to identify blood vessels before they are inadvertently damaged. Should bleeding occur, then sustained local pressure and/or ice usually suffices and the patient can be advised that bruising can be reduced with local application of arnica.16 Should post-injection headache occur then simple and effective analgesia is recommended.17,18 Infections are usually self-limiting and can be treated with antibiotics as required.19 These may be the result of inappropriate management of skin preparation prior to injection,20 or the presence of local infection at the time of injection.19 Serious complications associated with the injection of BoNT-A tend to be linked to pre-existing medical conditions such as

neuromuscular disease and severe hypersensitivity reactions. Botulinum toxin has the potential to exacerbate conditions such as myasthenia gravis, Eaton-Lambert syndrome or amytrophic lateral sclerosis secondary to the temporary blockage of acetylcholine release at the neuromuscular junction.21 Hypersensitivity reactions, including urticaria and life-threatening anaphylaxis, are often due to components that the toxin may have been prepared with, namely human albumin, lactose and sodium succinate.20 These can be managed with antihistamines, or in more serious cases of imminent airway compromise, practitioners should escalate care to the emergency services, whilst ensuring that the patient’s airway, breathing and circulation is intact. Deployment of standard medical emergency equipment is expected of practitioners; supplemental oxygen should be administered and, if available, an epinephrine autoinjector administered.22 There is one paper reported in the literature in 2005 regarding anaphylaxis and subsequent death from botulinum toxin administration; note that the woman was being treated for chronic neck and back pain rather than a cosmetic intervention.23 Death as a result of BoNT-A administration is incredibly unlikely and those reported to the FDA are typically as a result of therapeutic injections with significantly higher doses rather than following cosmetic interventions.24 However, this study by Cote et al. on reporting to the FDA highlights only data prior to 2005 in the US and does not take into account reporting elsewhere in the world, where reporting mechanisms are likely to vary.24 It should be noted that practitioners should be extra cautious treating patients who have had previous facial surgery due to distorted local anatomy and tissue fibrosis secondary to scarring.25 The upper face In this region, most complications are isolated to injections into the frontalis and associated depressor muscles (orbicularis oculi, corrugators and depressor supercilii) and include eyelid ptosis, brow ptosis and ‘spock’ eyebrow.25 This area is where most clinicians new to injectables begin to practice and a region that is considered by many to be ‘safe’, although this is not necessarily the case if simple rules are not adhered to (Table 1).25 It must be noted that with experience, and as injectors become accustomed to variations in anatomy and clinical outcomes of administration of BoNT-A, it is likely that injectors will move away from conventional ‘prescribed’ injection patterns.27,28 There are two crucial elements to assess when considering the brow: 1. The anatomy of the frontalis muscle 2. Any pre-existing brow ptosis. It is important to note that there is a difference between brow ptosis as a result of inadequate elevator activity (latent myogenic ptosis) and a true blepharoptosis, which are often confused.29 Be aware that patients may present to treat the forehead

1. Frontalis muscle as a result of rhytid formation in this area, that is in fact ‘compensated’ brow ptosis.30 This means that the patient is subconsciously elevating/contracting the frontalis in an effort to avoid brow droop.30 If the underlying cause of brow/upper lid ptosis (general ageing, levator dehiscence or dermatochalasia) remains unrecognised and untreated, then treating the frontalis with BoNT-A will cause the patient to complain of a ‘heaviness’ in the area as their compensatory mechanism has been temporarily eliminated by the toxin.31,32 King (2016) suggested that in those aged over 50, the glabella region should be treated first to observe the clinical reaction before injecting the forehead.25,33 In 2007, Olson highlighted that inappropriate central placement of product within the forehead can result in an unbalanced brow, widely referred to as the ‘Spock brow’.31 This may also result following inappropriate assessment of frontalis anatomy.It is well documented that by simply injecting further smaller volumes of BoNT-A in the lateral frontalis, 2cm above the brow will correct the ‘Spock brow’.34,35 In 2012, Braz and Sakuma did a retrospective analysis of pictures taken from 83 patients and identified three different anatomical variations in the frontalis muscle. These were: total pattern in 50.6% of cases, medial pattern in 25.3% of cases, and lateral pattern in 24% of cases. This observation prompted their suggestion that different injection patterns might be required to treat the frontalis based upon this anatomical variation.36 Mid-face The most common complications in the middle third of the face tend to be those affecting the periocular region. The reported incidence of upper eyelid ptosis following treatment of the upper third of the face (glabella and forehead region) with BoNT-A is up to 5.4%.37 This occurs as a result of injection or diffusion of the toxin into the

Always inject at the mid-forehead or above when treating the frontalis muscle. This should be at least 2cm above the brow in all patients and for older patients, ensure injections are at least 4cm above the brow. 2. Injection depth When treating the forehead, by injecting intradermally rather than intramuscularly, one study reported a lower incidence of ptosis with no reduction in results.26 3. Glabella muscle Always inject the glabellar at the same time as the forehead and never treat the frontalis muscle in isolation, particularly in patients over 50 years of age.2 Table 1: Recommendations for safe and successful BoNT-A treatments in the upper face. Table adapted from King 2016.25

Serious complications associated with the injection of BoNT-A tend to be linked to pre-existing medical conditions such as neuromuscular disease and severe hypersensitivity reactions

Anatomical region Complication

orbital septum, affecting the levator palpebrae superioris muscle.38 Total reversal of upper lid ptosis caused by BoNT-A can take up to three months. Therefore, in cases where ptosis affects vision or concerns the patient enough to warrant treatment, the use of 0.5% apraclonidine ophthalmic drops is recommended. Apraclonidine is an adrenergic agonist, which selectively increases eyelid elevation in the absence of levator function by stimulating Muller’s muscle to raise the lid by 1-2mm.39 It is important to appreciate the nearby associated musculature when treating the periocular region for lateral canthal lines (crow’s feet). BoNT-A injected into or diffusing into the inferior aspects of orbicularis oculi (OO) and/or the lower lid may result in increased scleral show.40 If severe, a lower lid ectropion may develop, ultimately leading to exposure keratitis41 or corneal damage.42 Should the aforementioned happen, treatment with lubricating eye drops and/or the application of an eyepatch at night may be indicated. Rarely, diplopia may occur if BoNT-A diffuses into the ocular muscles. Although temporary (usually four to six weeks) it can be severely debilitating and, whilst present, may require the patient to wear prism glasses to correct the oculomotor imbalance.43 The zygomaticus major (ZMa) and minor (ZMi) muscles have bony insertions (origins) at the lateral and medial aspects of the zygomatic buttress.44 Care must be taken when injecting the lateral or inferior aspects of the OO and control must be exercised on the depth of injection to ensure ZMa or ZMi are not treated,

Upper face and mid-face • Asymmetry resulting in ptosis of the lip on the ipsilateral side.45 • Ptosis of eyebrow or eyelid This is more evident when the patient is asked to • • Unmasking of pre-existing, compensated eyelid ptosis (weakening of frontalis) Impairment of eyelid function/ocular physiology (weakening of smile (asymmetric smile). Complications associated with BoNT-A injected into the periocular region orbicularis oculi) can be avoided by injecting at least 1cm away from • • Lower lid retraction/scleral show (weakening of orbicularis oculi) Lip ptosis (weakening of lip elevators when addressing nasal the lateral orbital margin.25 indications) • Atrophy Lower face and neck

Lower face • Asymmetry Over the years, BoNT-A has been used to • Oral motor insufficiency e.g. impaired ability to raise or lower effectively treat perioral rhytids.46 However, the lip given the complex arrangement of musculature • • • Impairment of dental show in animation (smiling) Impaired muscular support of lower face Dysphagia (when targeting platysma) that exists in this region, the risk of diffusion and over-dosage is highly likely.35 Hence, the perioral • Neck weakness (when targeting platysma) region is a treatment area considered suitable • Dry mouth (when targeting platysma) for experienced injectors only. Treatment in or Table 2: Potential adverse events from aesthetic use of botulinum toxin type A according to around the depressors (depressor labii inferioris, anatomical region. Table from Sundaram et al. 10 depressor anguli oris) is usually used to help lift corners of the mouth or contour the chin,47,48 but improper treatment may result in difficulty smiling and controlling the lower lip with eating and even drooling. 49,50 Notably, small doses with subsequent review and re-treatment are advocated: this was highlighted in the study by Carruthers (2010) that showed small doses of only BoNT-A in treating perioral ageing resulted in the least improvement, and so retreatment or combination with dermal fillers was recommended.51 Other areas in the lower face that may be indicated for treatment with BoNT-A, include the masseters.52 This is typically the case for patients who request jaw sculpting as a consequence of masseteric hypertrophy.53 Masseteric hypertrophy is commonly due to an underlying parafunctional habit, such as clenching or grinding.23 Despite the paucity of evidence towards the efficacy of treatment in this manner and one systematic review has found promising outcomes with this type of treatment.54 However, despite its so-called aesthetic effects, a 2018 study by Peng found that complications in 680 patients treated in the masseter muscles included:55 • Temporary mastication force decrease: 30% • Bruising: 2.5% • Headaches after 12 hours: 0.58% • Smile limitation: 0.15% • Paradoxical bulging: 0.49% • Sunken cheeks (sub-zygomatic volume loss): 0.44% • Sagging around the jawline: 0.20% The ‘Nefertiti’ neck lift, as it is often marketed as, is a popular BoNT-A treatment for those requesting a non-surgical lift and/or improvement in the appearance of unsightly platysmal bands.56 BoNT-A is injected superficially intradermally, yet despite relatively low dosage (50-70u – Allergan cosmetic dosing units), it has been observed that patients may struggle with ‘sit-up’ type movements57 amongst other potential complications based on systematic reviews58 (Table 3). Summary When administered by a medical professional with adequate training, the administration of BoNT-A for cosmetic purposes is largely a predictive and relatively safe exercise in the vast majority of

The evidence around longterm serious adverse events for the use of BoNT-A for cosmetic procedures is poorly reported

patients with most complications avoidable or transient in nature. The evidence around long-term serious adverse events for the use of BoNT-A for cosmetic procedures is poorly reported. Despite a general agreement on the common complications anticipated with BoNT-A treatment, consensus groups have highlighted the need for further clinical studies to better understand the impact in different regions of the face and have also suggested a need for panfacial assessment and appropriate treatment planning to improve outcomes.59 It is believed that most incidents typically occur in therapeutic cases where doses administered are significantly higher than recommended and/or where patient health may contribute as a confounding factor. Nevertheless, it is important that the aesthetic practitioner is vigilant in their approach to managing patients. Ultimately, this will allow for appropriate treatment and consent, as well as having a strategy in place should they be faced with complications, thereby ensuring the best outcomes for their patients.

Mr Sami Stagnell is a specialist oral surgeon with a clinical interest in facial aesthetics having actively practised in the field for seven years. He has completed an MSc in Skin Ageing and Aesthetic Medicine with the University of Manchester. He has contributed to the JCCP stakeholder groups representing dental interests, as well as publishing in the dental literature on facial aesthetics.

Ms Natasha Berridge is an oral and maxillofacial surgeon with a specialist interest in reconstructive aesthetic surgery and aesthetic medicine. A fellow of the Royal College of Surgeons and member of the Faculty of Dental Surgery, Ms Berridge has nine years of experience in treating facial hyperhidrosis and other maxillofacial conditions with botulinum toxin.

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