Elsevier

Disease-a-Month

Volume 48, Issue 5, May 2002, Pages 336-356
Disease-a-Month

Complications and adverse reactions with the use of botulinum toxin

https://doi.org/10.1053/mda.2001.25964Get rights and content

Abstract

Botulinum toxins are the causative agents of the severe food-borne illness botulism. With lethal doses approximating 10−9 g/kg body weight, these neurotoxins represent some of the most toxic naturally occurring substances. Regardless, botulinum toxin is considered a safe therapy for inappropriate muscle spasms with adverse effects being typically self-limited. This article deals with some of the complications that have occurred with these treatments. The greatest concern with the use of BOTOX is probably the formation of blocking antibodies leading to nonresponse of subsequent treatment. Prevalence of resistance is less than 5%. Most complications associated with its aesthetic use are few and anecdotal. Nevertheless, the common problems and pitfalls associated with aesthetic treatment of the various areas of the face and neck with botulinum toxin are discussed. Also included are recommendations as to how to avoid these very undesirable, yet common, problems.

Section snippets

Complications in treating conditions caused by muscle spasms

Many authors have published detailed reports on their experience in treating blepharospasm, torticollis, oromandibular dystonia, adductor and abductor laryngeal dystonia, lingual dystonia, limb dystonia, and hemifacial spasm.13, 14, 15

The therapeutic use of botulinum toxin generally has been safe and well tolerated.16 Effects of a localized injection of botulinum toxin to nearby or adjacent muscles are believed to be a result of local diffusion of toxin to that muscle, eg, ptosis after facial

Resistance to botulinum toxin

The greatest concern with the use of BOTOX is probably the formation of blocking antibodies leading to nonresponse of subsequent BOTOX injections. They do not cause hypersensitivity reactions to the injection of the substance. The only consequence is that BOTOX no longer is effective as a treatment. BOTOX resistance is a concern for both the treating physician and patient. Prevalence of BOTOX resistance is less than 5%32 and is likely associated with dose and frequency of treatment sessions but

Complications in the cosmetic use of botulinum toxin

Facial wrinkles are frequently caused by repeated muscle contraction. Botulinum A exotoxin can produce weakness or paralysis of these muscles and offers a novel approach for the treatment of certain facial rhytides. Botulinum toxin type A weakens the overactive underlying muscle contraction, causing a flattening of the facial skin and an improved cosmetic appearance.22, 42, 43, 44 This cosmetic use is not FDA approved and is thus considered off-label. The effect, although temporary, is

Brow

The most significant complication of treatment of the frontalis is brow ptosis and this should have been avoided by good selection of individuals to be treated and pre-injection of the brow depressors if necessary. BOTOX works best in younger female patients (20 to 45 years of age). In some older patients and in some male patients, redundant skin can be created under the brow (pseudo-ptosis), so such patients should be approached with caution. However, treatment of the brow depressors may be

Glabella

The most common complication in treatment of the glabellar complex is ptosis of the upper eyelid. This is due to diffusion of the toxin through the orbital septum, where it affects the upper eyelid levator muscle. This can occur as early as 48 hours or as late as 7 to 10 days after injection when the aesthetic effect is beginning to appear and can persist for up to two to four weeks. The 1 to 2 mm of ptosis is often initially only of subtle cosmetic significance, but as the day progresses the

Crows-feet

Reported complications in this area are bruising, diplopia, ectropion, or a drooping lateral lower eyelid and an asymmetrical smile due to injection of zygomaticus major. To avoid these complications inject at least 1 cm outside the bony orbit or 1.5 cm lateral to the lateral canthus, do not inject medially to a vertical line through the lateral canthus and do not inject close to the inferior margin of the zygoma. Violating these boundaries has on occasion also resulted in diplopia due to

Upper lip wrinkling and upper lip lines

Many of the muscles in the lower central face, especially those used in facial expression, are also involved in the functions of the mouth and cheeks. An asymmetric smile, biting the inside of a flaccid cheek or incompetence of the mouth manifest by drooling and dribbling are possible complications of the overly enthusiastic use of BOTOX in the lower face. However, small doses can be used satisfactorily, eg, into mentalis, nasalis, and levator labii superioris alaeque nasi. More recently BOTOX

Depressor angulioris

A common concern is a down-turn at the corner of the mouth producing a dejected appearance. This is often treated by the use of fillers such as injectable collagen. Brandt and Bellman have suggested that injection of platysma may produce improvement in this area.58 Some practitioners inject depressor angulioris directly to achieve improvement. The depressor angulioris muscle is found by instructing the individual to forcibly pull down the corners of the mouth. Inferior to a point 1 cm lateral

Naso-labial folds

Some physicians have treated levator labii superioris alaeque nasi in an attempt to soften the superomedial part of the naso-labial fold. They have used relatively low doses (2 to 3 U of BOTOX per side) including EMG localization of the site but report unimpressive response. In those individuals who did get softening of the folds, some showed lengthening of the upper lip which, of itself, is aging. There are better treatments for this problem in the majority of individuals although BOTOX should

Mentalis

Five to 10 U of BOTOX injected into the point of the chin can produce significant improvement in this appearance. It is important to keep well away from the mental fold although this may be softened by the injection. Injection into the mental fold area can easily produce an incompetent mouth. Massage after this injection is important.

Neck

BOTOX has been injected into platysma for some years to alleviate platysmal bands and horizontal neck lines. The use of larger doses to also improve the lower face and perhaps postpone a surgical rhytidectomy is more controversial. This technique has not produced any significant complications but the use of larger doses (75 to 100 U) can produce weakness of the neck flexors and dysphagia.

The 2 indications for injecting BOTOX into the platysma muscle are horizontal neck lines and hypertrophic

Complications in treating hyperhidrosis

Given the ability of BOTOX to diffuse radially in the axillary skin in a 1.5 cm radius, the physician must first identify the surface area of involvement using the starch-Iodine test. He can then place intercurrent doses of intradermal botulinum toxin spaced at intervals to allow overlap of the diffusion patterns. This will serve to maximize the paralytic effect on the eccrine units while minimizing the total dose needed to achieve dryness. A total dose of 50 U per axilla is normal in treating

Complications in treatment of migraine headaches

In a double-blind clinical study conducted by Silberstein et al,61 there were no reported cases of true eyelid ptosis, diplopia, facial nerve or expression problems, keratopathy, or idiosyncratic or allergic reactions attributable to BOTOX treatment. Two patients reported transient brow ptosis; other adverse effects were limited to transient local pain and ecchymosis at the injection site.61

In another double-blind clinical study conducted by Brin et al,62 the 75 U BOTOX group had a higher

Informed consent

It is prudent to inform patients about the potency and off-label use of the drug (the Food and Drug Administration and Canadian Health Protection Branch have approved BOTOX for the treatment of strabismus, benign essential blepharoplasm and facial nerve disorders), alternative therapies, duration of benefit, and the potential complications.

In the informed consent, it must be brought to the patient's attention that BOTOX has been approved by the FDA as a safe and effective therapy since 1989 for

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