The parasympathetic nervous system, through the release of Ach, causes a contraction of the iris sphincter muscle for pupillary contraction [ 13 , 14 ]. It is possible that the effects of botulinum toxin remain local in the target muscle at lower doses, but systemic anticholinergic effects of the drug can be seen at higher doses or when in closer proximity to vascular structures at the injection sites [ 13 , 15 , 16 ].
Treatment of glabellar rhytides with botulinum toxin can result in lagophthalmos and direct paralysis of the lacrimal gland, leading to dry eyes and superficial punctate keratitis [ 17 ]. Periorbital botulinum toxin injection can cause mydriasis of the pupil, resulting in acute angle closure attack. Cases have been reported in which the botulinum toxin was improperly injected into the vitreous cavity of a patient receiving treatment to the right medial rectus, resulting in increased intraocular pressure, decreased visual acuity and retinal detachment [ 18 ].
Paralysis of the frontalis is limited to the upper part of the frontalis and compensatory hyperactivation of the lower part of the frontalis muscle is possible in the lateral part of the forehead. Therefore, especially in people frequently using the frontalis muscle to raise their eyebrows or eyelids, exaggeration of previously unidentifiable wrinkles can take place on the border between the paralyzed frontalis muscle and non-paralyzed frontalis muscle. This complication is usually self-limiting and disappears spontaneously without any further treatment.
For the compliance and satisfaction of patients, an additional botulinum toxin injection into hyperactivated muscles can be performed. The most significant complications of treatment of the frontalis are brow ptosis and undesired eyebrow shape. These complications can be corrected with a botulinum toxin injection into muscles that antagonize the affected muscles; however, complications caused by the involvement of adjacent muscles are temporary and will spontaneously resolve as the botulinum toxin effects diminish.
They often result from overaggressive treatment with injections being administered too low on the forehead, or from poor patient selection. Treatment of the brow depressors can elevate the brow by 1—2 mm.
After injection, the distal ends of the eyebrows, which are normally positioned below the height of the eyebrow contour, become raised so that they are in a more superior position compared to the rest of the eyebrow, pointing upwards, forming the Mephisto sign. This condition occurs when the lateral fibers of the frontalis muscles are not sufficiently paralyzed compared to the medial fibers.
The probability of the occurrence of the Mephisto sign may vary depending on the length, structure and morphology of the frontalis muscle and injection skills of the clinician. This effect may last at least 3 months. In the treatment or prevention of the Mephisto sign we can use an additional dose of botulinum toxin to paralyze lateral fibers of the frontalis muscle [ 19 ]. Another complication is an asymmetric smile caused by injection into the zygomaticus major.
The injection should not be close to the inferior margin of the zygoma to avoid lip ptosis. Many of the muscles in the lower central face, especially those used in facial expressions, are also involved in the functions of the mouth and cheeks.
The necessity for complete oral competence may result in botulinum toxin lip treatments being contraindicated in scuba divers, wind instrument players, and professional vocalists. Peng et al. Different layers of the same muscles with opposite fiber direction may respond differently to the toxin. Muscular bulging during mastication is due to a superficial overcompensation of masseter muscle fibers in response to the neurotoxic weakening of the deep masseter [ 20 ]. Higher zygomas and less prominent cheek fat pads predispose to sunken lateral cheeks.
Another uncommon complication of the cosmetic use of botulinum toxin in the lower face is difficulty in opening the mouth, resulting from paralysis of the lateral pterygoid muscles. Iatrogenic paralysis of the lateral pterygoid muscle is treated by mechanotherapy. Toxin diffusion to the parotid gland through the posterior part of the masseter muscle is due to xerostomia, requiring the use of sialagogues [ 20 ].
The cosmetic use of Botox is safe even in cases of repeated injections. On the other hand, the long-lasting cosmetic use of botulinum toxin can trigger permanent changes in facial expression, and an expressionless, mask-like face. Lack of facial animation or permanent changes in facial expression may be undesirable in some cases. For individuals who have a greater need for facial animation, who must communicate with children, for actors, and broadcasters, such an outcome may have negative professional consequences.
The potentially serious events are sequelae due to the systemic spread of toxin leading to botulism-like features or systemic anaphylactic reactions. The cosmetic use of botulinum toxin rarely causes severe side effects. The frequency of serious side effects is 33 times higher for therapeutic than for cosmetic cases. The median botulinum toxin dose is 4 times higher in reports for therapeutic cases than cosmetic cases [ 22 ].
They are classified as a life-threatening experience requiring intervention to prevent permanent damage and associated with patient hospitalization or prolongation of existing hospitalization, and persistent or significant disability [ 22 ]. Serious adverse effects after cosmetic use of botulinum toxin include dysphagia, muscle weakness, and allergic reactions [ 22 , 23 ].
Dysphagia and muscle weakness are common symptoms of botulism. Cosmetic treatment of cervical wrinkles and lines usually requires larger doses of botulinum toxin and increases the risk of serious side effects. Platysmal injections in large doses 50 units and higher to correct prominent vertical bands and horizontal neck lines may cause weakness of the neck flexors and temporary dysphagia, and, in rare cases, hoarseness.
Older patients and larger doses increase the possibility of direct botulinum toxin injections or localized diffusion into the deeper cervical structures.
Botulinum toxin can spread to a distance of 30—45 mm from the injected muscles to the adjacent muscles, even if these muscles are separated by fasciae. Neck muscles are prone to diffusion of botulinum toxin, and paralysis of the wrong muscles leads to dysphonia, dysphagia or dystonia. Mild and transient cervical discomfort usually occurs 2 to 5 days after injection.
Dysphagia occurs on average 9. Clinically significant dysphagia resolves spontaneously within 2 weeks. If severe dysphagia is noted, a temporary change to a soft diet may be instituted and emotional support provided until full recovery occurs. Patients with severe dysphagia require nasal feeding or intravenous nutrition to maintain the water-electrolyte balance.
One of the most common serious adverse effects of botulinum toxin is muscle weakness. This may involve injected muscles as well as adjacent muscles, or it may manifest as generalized muscle weakness.
This weakness recurred a year after the first injection [ 24 , 25 ]. This wide spectrum of symptoms associated with muscle weakness or paralysis, dysarthria, dysphonia, dysphagia and respiratory arrest is known as botulism. The first symptoms of botulism may be severe and long-lasting headache and fatigue. According to Bai et al. Botulism is dose-dependent and results from the diffusion of the botulinum toxin into adjacent muscles from the injected muscles.
It is interesting that botulism can occur even a few years after continued injections. Usually, toxic effects of botulinum toxin can appear at the 10 th or 11 th injection, after prior uncomplicated injections. The clinical symptoms of botulism after cosmetic use occur 0 to 36 days after injection, mainly between the 2 nd and 6 th day following the operation [ 26 ]. Treatment is based on the administration of neurotrophic drugs, systemic support and symptomatic treatment, and the injection of botulinum antitoxin serum.
In cases of moderate to severe botulism, vital signs should be monitored closely. Severe-case patients should accept tracheal intubation and mechanical ventilation.
Patients with a negative skin test should receive 10 IU of antitoxin serum via intramuscular injection once every 12 h; patients with a positive or weak positive skin test should receive 10 IU via desensitization injection once a day [ 26 ]. Early application of botulinum antitoxin serum and certain symptomatic support treatments, such as active infection prevention, is important for botulism treatment. The earlier the treatments are performed, the better the effects are [ 26 ].
The mechanism responsible for the generalized diffusion of botulinum toxin is not known. Hypotheses proposed concern either systemic spread or retrograde axonal spread of toxin. It is not clear whether the generalized diffusion is due to the spread of botulinum toxin or of its inactive metabolites [ 27 ].
The toxin may be able to traverse through an intact vessel wall. In addition, accidental intravenous delivery of the toxin may occur when it is injected into muscle [ 28 ]. Diffusion of botulinum toxin to contralateral muscles has also been reported. Moreover, experimental studies have shown that botulinum toxin receptors exist in the central nervous system and a small amount of botulinum toxin crosses the blood-brain barrier.
This raises the possibility that botulinum toxin is transported retrogradely, similarly to tetanus toxin, and may cause centrally mediated side effects.
Another theory postulated relates to absorption of a small amount of botulinum toxin into the bloodstream and its systemic action [ 4 ]. In addition to the mechanism of generalized diffusion, another source of severe side effects is anaphylactic shock. It is attributed to the chemical structure of the drug, resulting in hypersensitivity reactions.
Using standard emergency protocols and medications such as epinephrine and methylprednisolone is advised when indicated, rather than diphenhydramine, because of its anticholinergic effects. There is no difference in the frequency of anaphylactic shock between the cosmetic and therapeutic use of botulinum toxin [ 29 ].
Repeated injections cause immune complexes to form in the botulinum toxin, which induces blocking of antibodies. Other immune-mediated reactions are the source of both hypersensitivity and immunoresistance to botulinum toxin.
Other types of BoNT-A have different antigenicity. It was reported that incobotulinumtoxinA Xeomin is characterized by reduced antigenicity [ 30 ]. Antibody development against various components of botulinum toxin complex is evidence of systemic botulinum toxin exposure.
The factors that contribute to antibody formation include longer duration of treatment, a shorter time interval between injections, larger overall doses, and decreased purity of botulinum toxin preparation [ 6 ]. Immunoresistance is another entity that has been clinically described in selected patients, especially those injected with large doses in multiple treatment sessions [ 4 ].
Clinically significant botulinum toxin resistance is less common in patients who receive the lower doses of botulinum toxin that are typically administered in cosmetic treatments. The experienced team of board-certified dermatologists and licensed medical professionals at Spa at the Dermatology and Skin Cancer Institute are proud to offer a long list of innovative and exciting treatment options to help Philadelphia, PA patients look and feel their very best.
If you are looking for a convenient and effective solution for facial lines and wrinkles, then BOTOX may be right for you. Learn everything you need to know about BOTOX therapy here, including what kind of results you can expect and how long they will last. BOTOX is a neurotoxin that has several different medical and clinical uses.
It is arguably most well-known for being an effective treatment for dynamic facial lines and wrinkles, though it is also beneficial in treating overactive sweat glands, various bladder symptoms, and even headaches.
When injected into the face, BOTOX binds with certain structures in the nervous system to prevent the muscles from contracting. On occasion, some of the Botox may seep into the upper eyelid and paralyze the muscle that holds the upper eyelid up.
Droopy eyelids should disappear within four to six weeks, but you can alleviate symptoms by trying these treatments:.
Choosing the right doctor can greatly reduce the risk of side effects such as drooping eyelids. Botox remains overwhelmingly safe when performed by a qualified doctor or surgeon. Most doctors rarely see adverse effects, other than mild bruising or swelling. However, side effects may indicate an allergic reaction and would be cause for you to seek immediate help.
There have been no cases of systemic body-wide reactions to Botox, and no one has died. Usually, an adverse side effect of Botox will present itself within the first week following treatment. A delayed allergic reaction to botox is highly unlikely. However, if you are experiencing any symptoms of an allergic reaction, you should speak to your doctor immediately. If you experience any of the following symptoms, you could be having an allergic reaction:. If you think you are having an allergic reaction to your Botox injections, contact your doctor or surgeon immediately.
If you experience severe swelling of the face or difficulty breathing, call Do not rub or massage the treated areas for 24 hours. This may help prevent the toxin from spreading to a different area. You can return to your normal activities right after the procedure. Botox injections usually begin working one to three days after treatment. Depending on the problem being treated, the effect may last three months or longer. To maintain the effect, you'll need regular follow-up injections.
Explore Mayo Clinic studies of tests and procedures to help prevent, detect, treat or manage conditions. Botox injections care at Mayo Clinic. Mayo Clinic does not endorse companies or products. Advertising revenue supports our not-for-profit mission. This content does not have an English version.
This content does not have an Arabic version. Overview Botox injections are noted primarily for the ability to reduce the appearance of facial wrinkles.
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