CPD: Exploring Toxin Complications

Exploring Botulinum Toxin Complications

Dr Martyn King provides an introduction into complications caused by botulinum toxin injections and outlines the methods of prevention

Botulinum toxin treatment is the most popular non-surgical aesthetic procedure worldwide, with millions of treatments being performed each year.1 Although it is generally considered a safe procedure, complications can and do occur. A 2022 literature review by Zargaran et al. looking at a total of 17,352 injection sessions reported a complication rate of 16% following botulinum toxin injections for aesthetic use (with an incidence of bruising at 5%, headaches at 3% and unintended muscle weakness at 2%).2 It is important that treatments are performed by medical practitioners in an appropriate clinical setting having received in depth training in all aspects of botulinum toxin and facial anatomy to help mitigate risks (Figure 1). It is also essential that a licensed botulinum toxin is used for treatments that is sourced from a reputable supplier and it is appropriately transported and stored.

The toxin used and dilution volume may also be important when considering risk of complications. Finally, patient selection is paramount, taking into consideration absolute and relative contraindications (Table 1), medical history, and psychological concerns. Bruising

There is usually none to a minimum amount of bleeding when performing botulinum toxin treatments and bruising can ensue. If a bruise does occur, it is usually small and discreet but can cause concern for patients who do not tell friends and family that they have treatment. Several factors can increase the risk of ecchymosis,2 including older age with thin and fragile skin, alcohol, certain medications, such as anti-inflammatory painkillers, herbal and vitamin supplements, and treatment technique.3,4,5 The risk can be reduced by avoiding certain medication and supplements, such as fish oils, omega-3 fatty acids, garlic, high dose vitamin E and gingko biloba.5 Practitioners may also reduce the instances through the application of cold compresses, topical or oral products (such as arnica or bromelain) and the use of imaging technology (such as ultrasound or infra-red technology) as they allow for the direct visualisation of veins.6

Ptosis

Glabellar lines

Procerus & corrugator supercilii muscle Smooth vertical lines

Sagging eyebrow

Orbicularis oculi muscle Eyebrow lifting

Forehead lines

Frontalis muscle Soften horizontal forehead lines

Crow’s feet

Orbicularis oculi muscle Smooth skin from the outer corner of the eye

Marionette lines

Depressor anguli oris muscle Lifting corners of the mouth

Chin dimpling

Mentalis muscle Smoothing dimples

Bruxism

Masseter muscle More oval face

Gummy smile

1. Levator labii superioris 2. Levator labii superioris alaeque nasi 3. Zygomaticus minor Reduce an excessive gingival display

Platysmal neck bands

Platysma muscle Smoothing the bands and neck Ptosis refers to droopiness or abnormal downward displacement of a body part, and can occur anywhere in the body, although the most common area to be affected is the eye, both through the lid and brow.7

Brow ptosis Depression of the brow can occur when excessive dosage is used, or if the injection area is too low or in patients where they are reliant on an increased resting tone in their frontalis muscle to keep their brows in position.7 This latter point can be demonstrated by asking the patient to look straight ahead with their head in a neutral position and asking them to close their eyes. If their brows drop when they close their eyes, they are not suitable for forehead treatment with botulinum toxin as this results in brow ptosis and instead may be more suitable for a surgical forehead lift.7

The incidence of brow ptosis is 1%,8 but should it occur, the brow can be lifted by injection of a few units of botulinum toxin (1-2 units of Botox/Bocouture at each injection site or 2.5-5 Speywood units of Azzalure) just beneath the arch and tail of the brow.7 However, caution needs to be taken to not cause a subsequent lid ptosis. In my experience, lowering the contralateral brow to improve symmetry may produce a more cosmetic outcome.

Absolute contraindications

• Neuromuscular transmission disorder (such as myasthenia gravis, Eaton Lambert syndrome and amyotrophic lateral sclerosis) • Current or recent aminoglycoside antibiotic use • Infection or inflammation at injection site • Previous allergic reaction to botulinum toxin treatment or human albumin solution • Pregnancy • Breast feeding • Children (under 18 years of age) • Chronic disease/poor general health • Poor wound healing • Immunocompromise (acquired or drug-induced) • Undergoing treatment for cancer • Patients on anticoagulants or blood clotting disorders • Dysphagia • Eye movement disorders • Mental health problems/body dysmorphia

Relative contraindications

Table 1: Contraindications of botulinum toxin treatment16

Lid ptosis Lid ptosis can occur when toxin spreads from the glabellar treatment area and affects the levator palpebrae superioris muscle, often from injections administered too low or excessive dosage.9 Nestor et al. conducted a literature review including more than 17 journal articles and involving more than 6,000 patients, specifically looking at eye lid anatomy, pathogenesis, presentation, prevention and treatment of eyelid ptosis secondary to botulinum toxin treatment. Research shows that the risk can be reduced by ensuring that injection into the lateral corrugator supercilia muscle is superficial. If lid ptosis does occur, it can often be improved using 1% apraclonidine (Iopidine) eye drops, one or two drops up to three times a day.9 It is an alpha-adrenergic receptor antagonist and a mydriatic which acts on Müller’s muscle (the superior tarsal muscle) and can lead to a 1-2mm elevation of the upper lid.9 In my experience, lower lid ptosis may occur when treating the eye roll, which can be caused by injecting too much product into the area. Anecdotally, it’s known that a maximum dosage of 2 units of Botox and Bocouture, and 5 Speywood units of Azzalure should be used for this indication. Patients who have excessive skin laxity or prominent infraorbital fat pads are reliant on a small degree of hyperactivity of their orbicularis oculi muscle to prevent lower lid ptosis so if this is impeded by the administration of botulinum toxin, this can lead to some drooping. A snap test – where you pinch the skin and let it go to see how quickly it reverts back into place – should be performed prior to treatment. The lower eyelid skin should retain its original appearance within two seconds of performing the snap test. If this does not occur, it suggests lower lid skin laxity and the patient is unsuitable for treatment in this area.

Perioral ptosis

Smile and lip irregularities are possible from several botulinum toxin treatments, including treatment of the upper lip rhytids (smoker’s lines), gummy smiles, masseters, melomental lines or mentalis. If the lateral canthal lines (crow’s feet) are injected too inferiorly, with excessive dosage or too great a dilution, the toxin may affect the zygomaticus major. This muscle extends from the zygomatic arch to the corner of the mouth at the modiolus and is responsible for lifting the corner of the mouth with smiling. If it is inadvertently affected by botulinum toxin, the patient will have an asymmetric smile. There is no specific treatment to rectify this, and patients often need to wait for the effects to wear off. Some patients may opt to have some toxin injected into the opposite side of the face to improve symmetry.7 Semchyshyn and Sengelmann published their clinical study of 18 patients, demonstrating that smoker’s lines can be improved by the injection of 1-2 units of Botox/Bocouture or 2.5-5 Speywood units of Azzalure in four sites, avoiding the lateral quarters and superficial only.10 Even with successful treatment, a common side effect is that patients may notice some weakness making it difficult to whistle or drink through a straw and they should be counselled on this prior to treatment. It is not a suitable procedure for those who rely on their voice for their profession, such as singers. Over treatment, injections too deep, too great a dilution, or injections too low can lead to some upper lip ptosis and irregularities on movement. For the treatment of ‘gummy smiles’, the levator labii superioris alaeque nasi is injected because this muscle is responsible for elevating the upper lip and dilating the nostrils in a snarl expression. However, if too high a dose is used, this can lead to a ptosis of the lip when smiling, leading to a lack of show of the upper teeth.11

When treating the masseter muscles, injections should be placed deep, at least 1cm below the skin, so needles of 8mm length are not suitable for this treatment. If treatment is too anterior, there is a risk of weakening the risorius muscle, leading to a narrowed smile on animation. The risorius may be absent or vestigial in some people.12 A depressed corner of the mouth can be improved by injections into the depressor anguli oris muscle; this is a triangular muscle originating from the mandible and inserting into the corner of the mouth (Figure 1). It is safer to inject this muscle inferiorly to ensure that other expression muscles at the modiolus are not affected.12 Lower lid ptosis can also occur if the depressor labii inferioris is inadvertently targeted when treating the mentalis muscle for a dimpled chin. Injections in this area should be into each muscle pair, low down after palpating the muscle.12

The mephisto or Spock brow

The mephisto or Spock brow refers to the instance of a raised outer end of the brow, producing an intimidating and undesired appearance. This complication can happen when insufficient dosage of botulinum toxin is used in the lateral parts of the frontalis muscle and there is a paradoxical increase in muscle activity when the central portion is relaxed or from treating the glabellar complex too high and hitting frontalis. It is easily corrected by injection of further units in the lateral aspect of the upper frontalis muscle.13 However, over-correction may result in a brow ptosis so practitioners must take great care in their approach.7

Malar oedema

The orbicularis oculi muscle is a sphincter muscle and part of its function is in aiding lymphatic drainage in the under-eye area. By treating the crow’s feet too medially, it may impair the sphincter activity and result in the accumulation of fluid in this region.4 Malar oedema is more common in certain people and patients seeking treatment should be asked if they are prone to swelling in this region, for example, after crying or a poor night’s sleep. The incidence is also higher in patients taking certain medications, such as non-steroidal

anti-inflammatories, oestrogen, and calcium channel blockers.14 Treatment options include head elevation, cold compresses, and lymphatic drainage.14

Hypersensitivity reactions

There have been very few reported hypersensitivity reactions to botulinum toxin. However, if bacteriostatic saline has been used as a diluent, the benzyl alcohol added as a bacteriostatic preservative can lead to a localised reaction, including itching, hives, erythema, or a systemic reaction in more severe cases.15

Headache

Although toxin is a common treatment approach for migraines, a complication of toxin can actually be headaches. Clinical studies have shown that headaches are a common side-effect when treating horizontal forehead lines.16 It is unknown why this occurs, but could be due to a change in tension in the frontalis muscle or excessive contraction of the muscle in patients who have had treatment and are ‘testing’ the effect. In the author’s view, this latter point is corroborated by the observation that patients who have never had treatment before are more likely to develop a headache than those who have had treatments previously.16

Muscle twitching

Although this is an uncommon effect of botulinum toxin treatment, muscle twitching can occur, usually starting within a few days of treatment and more frequently around the eye when treating crow’s feet. Muscle twitching is listed as an uncommon side effect in the summary of product characteristics possibly due to some compensatory over-activity in neighbouring muscle that has not been affected by botulinum toxin treatment. It will often last a few days up to a week and settle spontaneously.16

Conclusion

Botulinum toxin treatments are one of the most popular treatments in aesthetic clinics and complications tend to be infrequent and relatively minor when conducted by an appropriately trained and experienced practitioner. However, it is important that injectors continuously audit their own practice and monitor their own continued professional development to ensure they are following best practice. If an unexpected complication occurs as the result of the product being used, it is important that the practitioner informs the pharmacovigilance department of the manufacturer and reports this to the MHRA via the Yellow Card system.

Dr Martyn King is the director of Cosmedic Skin Clinic, Cosmedic Online and Cosmedic Pharmacy. He is medical director of the ACE Group World, vice-chair of the Joint Council of Cosmetic Practitioners, a member of the British College of Aesthetic Medicine and board member for the British Association of Sclerotherapists. Qual: MBChB, MSc, PGDip, PGCert The ACE Group World will be holding its conference at CCR this year on October 13 and 14, scan the QR code to register your interest!

Aesthetics Clinical Advisory Board Member Dr Souphi Samizadeh reviewed this article and says...

Botulinum toxin injections are the most requested non-surgical cosmetic procedure carried out internationally and this trend has remained the same for many years. Botulinum toxins are potent toxins and can cause botulism and lead to death. As biological drugs for therapeutic and cosmetic purposes, they have a longstanding safety and efficacy profile. However, to benefit from its safety and efficacy, it should be administered by healthcare professionals with knowledge of anatomy, physiology, pharmacology and patient management and reputable and safe products to be obtained. Aesthetic practitioners must understand that various formulations are not interchangeable and be wary of fake or unlicensed products as even cosmetic doses cannot rule out chances of botulism. This is an excellent article on some of the complications caused by injections of botulinum toxin for cosmetic purposes (face) and the methods of prevention.

Test your knowledge! Complete the multiple-choice questions and go online to receive your CPD certificate!

Questions

1. Which of the following is an absolute contraindication to botulinum toxin treatment?

2. Which of the following does NOT increase the risk of bruising?

Possible answers

a. Huntington’s disease b. Multiple sclerosis c. Parkinson’s disease d. Amyotrophic lateral sclerosis

a. Bromelain b. Alcohol c. Ibuprofen d. Cod liver oil

3. What can lid ptosis be treated with? a. Bimatoprost eye drops b. Apraclonidine eye drops c. Timolol eye drops d. Chloramphenicol eye drops

4. ‘Gummy lines’ can be improved by injecting which muscle? a. Levator labii superioris alaeque nasi b. Zygomaticus major c. Orbicularis oris d. Depressor angular oris

5. Which of the following is not effective for the management of malar oedema? a. Cold compresses b. Oral steroids c. Calcium channel blockers d. Lymphatic drainage

Answers: D, A, B, A, C