Application of botulinum toxin in dermatology and cosmetology

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Piyu Parth Naik Dermatology, Saudi German Hospitals and Clinics, Dubai, United Arab Emirates Communications: Piyu Parth Naik Dermatology, Saudi German Hospitals and Clinics, Burj Al Arab, Dubai, United Arab Emirates Opposite phone +971 503725616 email [email received Protection] Abstract: Botulinum toxin (BoNT) is a neurotoxin produced by Clostridium botulinum bacteria. It has a well-known efficacy and safety in the treatment of focal idiopathic hyperhidrosis. BoNT contains seven different neurotoxins; however, only toxins A and B are used clinically. BoNT has recently been used for off-label treatment of various skin diseases. Scar prevention, hyperhidrosis, wrinkles, small sweating moles, hair loss, psoriasis, Darier’s disease, bullous skin disease, sweat herpes and Raynaud’s phenomenon are some of the new indications of BoNT in cosmetics, especially in dermatology Non-cosmetic aspects. In order to use BoNT correctly in clinical practice, we must thoroughly understand the functional anatomy of simulated muscles. An in-depth literature search was conducted to update all dermatological-oriented experiments and clinical trials on the elements of BoNT in order to provide a general overview of the use of BoNT in dermatology. This review aims to analyze the role of botulinum toxin in dermatology and cosmetology. Keywords: botulinum toxin, botulinum toxin, botulinum, dermatology, cosmetology, neurotoxin
Botulinum neurotoxin (BoNT) is naturally produced by Clostridium botulinum, which is an anaerobic, gram-positive, spore-producing bacterium. 1 To date, seven BoNT serotypes (A to G) have been discovered, and only types A and B can be used for therapeutic use. BoNT A (Oculinum) was approved by the U.S. Food and Drug Administration (FDA) in 1989 for the treatment of blepharospasm and strabismus. The therapeutic value of BoNT A was determined for the first time. It was not until April 2002 that the FDA approved the use of BoNT A to treat glabellar lines. The FDA approved BoNT A for the treatment of the frontal line and lateral canthal line in October 2017 and September 2013, respectively. Since then, several BoNT formulations have been introduced to the market. 2 Since its commercialization, BoNT has been used to treat cramps, depression, hyperhidrosis, migraine, and aging of the neck, face, and shoulders in the medical and cosmetic fields. 3,4
Clostridium botulinum secretes a three-protein complex that includes 150 kDa toxin, non-toxic, non-hemagglutinin protein, and non-toxic hemagglutinin protein. Bacterial proteases break down the toxin into a double-stranded active product with a 50 kDa “light” chain and a 100 kDa “heavy” chain. After being transported to the presynaptic nerve terminal, the heavy chain of the active toxin binds to synaptic vesicle glycoprotein 2, promoting the endocytosis of the toxin-glycoprotein complex, and releasing the toxin light chain into the synaptic space. Toxin light chain cleavage vesicle-associated membrane protein/synaptoxin (BoNT-B, D, F, G) or synaptosome-associated protein 25 (BoNT-A, C, E) to prevent the release of peripheral motor neuron axons Acetylcholine also causes transient chemical denervation and muscle paralysis. 2 In the United States, there are four commercially available BoNT-A preparations approved by the FDA: incobotulinumtoxinA (Frankfurt, Germany), onabotulinumtoxinA (California, U.S.), prabotulinumtoxinA-xvfs (California, U.S.), and abobotulinumtoxinA (Arizona, U.S.); and One kind of BoNT-B: rimabotulinumtoxinB (California, USA). 5 Guida et al. 6 commented on the role of BoNT in the field of dermatology. However, there has not been a recent review on the application of BoNT in the field of dermatology and beauty. Therefore, this review aims to analyze the role of BoNT in dermatology and cosmetology.
Specific keywords include botulinum toxin, oily skin, rosacea, facial flushing, scars, wrinkles, hair loss, psoriasis, bullous skin disease, Darier’s disease, exocrine moles, sweat herpes, Raynaud’s phenomenon, hyperhidrosis In response, dermatology, and beauty, article searches are conducted in the following databases: Google Scholar, PubMed, MEDLINE, Scopus, and Cochrane. The author is mainly looking for articles about the role of BoNT in dermatology and cosmetology. A preliminary literature search revealed 3112 articles. Articles published between January 1990 and July 2021 describing BoNT in dermatology and cosmetology, articles published in English, and all research designs are included in this review.
Canada approved the use of BoNT in the cosmetic treatment of local muscle spasms and eyebrow wrinkles in 2000. The US FDA approved the use of BoNT for cosmetic purposes on April 15, 2002. BoNT-A indications recently used in cosmetic applications include frown lines between the eyebrows, crow’s feet, rabbit lines, horizontal forehead lines, perioral lines, mental folds and chin depressions, platysma bands, mouth frowns, and horizontal neck lines. 7 The indications for botulinum type A approved by the US FDA are moderate to severe frown lines associated with excessive activity of the prefrontal and/or frown muscles between the eyebrows, and moderate to severe lateral canthal lines associated with excessive activity of the orbicularis muscle. And the moderate-to-severe horizontal forehead line associated with excessive frontal muscle activity. 8
Sebum helps provide fat-soluble antioxidants to the skin surface and has antibacterial properties; therefore, it acts as a skin barrier. Too much sebum can clog pores, breed bacteria and may cause skin inflammation (for example, seborrheic dermatitis, acne). Previously, relevant knowledge about the effects of BoNT on sebum has been disclosed. 9,10 Rose and Goldberg10 tested the effectiveness and safety of BoNT on 25 people with oily skin. BoNT (abo-BNT, a total dose of 30-45 IU) is injected into 10 points of the forehead, which significantly improves patient satisfaction and reduces sebum production. Min et al. randomly assigned 42 subjects with forehead wrinkles to receive 10 or 20 units of BoNT at five different injection sites. Both groups received BoNT treatment, which resulted in a significant reduction in sebum at the injection site and a sebum gradient around the injection site. At the 16th week, the sebum production of the two treatment groups returned to normal levels, and with the increase in the injection dose, the curative effect did not significantly improve.
The mechanism by which intradermal injection of botulinum toxin leads to reduced sebum secretion is not fully understood, because the effects of the nervous system and acetylcholine on the sebaceous glands have not been fully described. The neuromodulatory effects of BoNT most likely target local muscarinic receptors in the erector pili muscle and sebaceous glands. In vivo, nicotinic acetylcholine receptor 7 (nAchR7) is expressed in human sebaceous glands, and acetylcholine signaling increases lipid synthesis in a dose-dependent manner in vitro. 11 More research is needed to determine who is the most important candidate and the best injection procedure and dosage (Figure 1A and B).
Figure 1 The upper image (A) of a patient with obvious oily skin, while at the other pole, the lower image (B) of the same patient after two BoNT treatments shows a significant improvement. (Technology: 100 units, 2.5 ml of intradermal BoNT-A was injected once into the forehead. A total of two similar treatments were performed 30 days apart. The good clinical response lasted for 6 months).
Rosacea is a common inflammatory skin disease characterized by facial flushing, telangiectasia, papules, pustules, and erythema. Oral medications, laser therapy, and topical medications are commonly used to treat facial flushing, although they are not always effective. Another unpleasant symptom of menopause is facial flushing. Several studies have shown that BoNT can help treat menopausal hot flashes and rosacea. 12-14 The impact of BoNT on the Dermatological Quality of Life Index (DLQI) of patients with facial flushing will be investigated in a future pilot study. 15 BoNT was injected into the cheek once, up to a total dose of 30 units, resulting in a significant drop in DLQI at two months. According to Odo et al., BoNT significantly reduced the average number of menopausal hot flashes on the 60th day. 12 The effect of abo-BoNT was also studied in 15 patients with rosacea. Three months later, 15-45 IU of BoNT was injected into the face, which resulted in a statistically significant improvement in erythema. 13 In research, adverse reactions are rarely mentioned.
The increased flushing of BoNT is one of the possible reasons for its strong inhibition of the release of acetylcholine from peripheral autonomic neurons of the skin vasodilation system. 16,17 It is well known that inflammatory mediators such as calcitonin gene-related peptide (CGRP) and substance P (SP) are also inhibited by BoNT. 18 If local skin inflammation is reduced and controlled, erythema may disappear. In order to evaluate the role of BoNT in rosacea, extensive, controlled, randomized studies are needed. BoNT injections for facial flushing have additional advantages because they can reduce the strain on facial suppressors, thereby improving fine lines and wrinkles.
Many people now realize the importance of actively avoiding scars in the treatment of postoperative scars. The tension acting on the edge of the wound during the healing process is a key factor in determining the final appearance of the surgical scar. 19,20 BoNT prevents the release of the acetylcholine neurotransmitter, almost completely eliminating the dynamic muscle strain on the healing wound from the peripheral nerve. The tension-relieving properties of BoNT, as well as its direct inhibition of fibroblast and TGF-1 expression, indicate that it can be used to avoid surgical scars. 21-23 The anti-inflammatory effect of BoNT and its effect on the skin vasculature can reduce the stage of the inflammatory wound healing process (from 2 to 5 days), which may help prevent scar formation.
In various studies, BoNT can be used to prevent scars. 24-27 In an RCT, the safety and effectiveness of early postoperative BoNT injection in 15 patients with scars from thyroidectomy were evaluated. 24 Fresh scars (within 10 days of thyroidectomy) were given BoNT (20-65 IU) or 0.9% normal saline (control) once. Half of the BoNT treatment showed significantly better scar score and patient satisfaction than normal saline treatment . Gassner et al.25 investigated whether injection of BoNT into the face after a forehead laceration and resection can heal facial scars. Compared with placebo (normal saline) injection, BoNT (15-45 IU) was injected into the postoperative scar after wound closure within 24 hours to enhance the cosmetic effect and wound healing.
Dynamic and static wrinkles are formed by overactive muscle tissue, light damage and aging, and patients believe that they make them look tired or angry. It can treat facial wrinkles and provide people with a more relaxed and refreshing appearance. The FDA currently has exclusive authorization for BoNT to treat the periorbital and interbrow line. BoNT is used to treat masseter hypertrophy, gingival smile, platysma band, mandibular margin, chin depression, horizontal forehead line, curved smile, perioral line, horizontal nasal line and sagging eyebrows. The clinical effect lasts for about three months. 28,29 (Figure 2A and B).
Figure 2 The upper image (A) before the Botox injection of a case shows that the horizontal forehead line and the glabellar line make the subject look angry. On the other hand, the lower image of the same case (B) after two meat After the toxin injection, these lines are removed comfortably. (Technology: 36 units, 0.9 mL of intradermal BoNT-A was injected into the forehead at a time. The injection site was marked with a skin pencil before treatment. A total of two similar treatments were performed, 30 days apart).
BoNT can enhance the patient’s emotional and perceived confidence when used with the reduction of rhythm. An improvement in the FACE-Q score was observed after the treatment of moderate to severe glabellar lines. Even after 120 days, when the clinical effects of BoNT should have diminished, patients reported improvements in mental health and improved facial attractiveness.
Unlike the automatic reinjection of BoNT every three months to obtain the best clinical and psychological response, the practitioner should discuss with the patient when retreatment is necessary. 30,31 In addition, BoNT has been successfully used to prevent and treat migraine in neurology, improving the quality of life and well-being of patients32 (Figure 3A and B).
Figure 3 The upper image (A) of the subject shows that the periorbital lateral lines give a feeling of aging and exhaustion. On the other hand, the lower image (B) of the same case eliminates these lines and raises them after the injection of Botox The side eyebrows are clearly visible. After sitting down this time, this theme also expresses a wealth of emotional health. (Technology: 16 units, 0.4 ml intradermal BoNT-A is injected once, once in each lateral periorbital area. Only once ended up with a significant response lasting 4 months.)
Alopecia areata, androgenetic alopecia, headache alopecia and radiation-induced alopecia have been treated with BoNT-A. Although the exact mechanism by which BoNT helps hair regenerate is uncertain, it is speculated that by relaxing the muscles to reduce microvascular pressure, it can improve the oxygen supply to the hair follicles. In 1-12 courses, 30-150 U is injected into the frontal lobe, periauricular, temporal and occipital muscles (Figure 4A and B).
Figure 4 The left half (A) of the clinical photo shows the type 6 male pattern baldness of a 34-year-old man according to the adopted Norwood-Hamilton classification. In contrast, the same patient showed a downgrade to type 3V after 12 botulinum injections (B). (Technology: 100 units, 2.5 mL of intradermal BoNT-A was injected into the top area of ​​the head once. A total of 12 similar treatments separated by 15 days resulted in an acceptable clinical response, lasting 4 months).
Although most studies show clinical improvements in hair density or growth and high patient satisfaction, further RCTs are needed to determine the actual effect of BoNT on hair growth. 33-35 On the other hand, multiple BoNT injections for forehead wrinkles have been confirmed to be related to the occurrence of frontal hair loss. 36
Several studies have shown that the nervous system plays a role in psoriasis. The concentration of nerve fibers in the skin of psoriasis is high, and the levels of CGRP and SP derived from sensory nerves are high. Therefore, clinical evidence showing the remission of psoriasis after the loss of innervation is increasing, and nervous system damage or nerve function supports this hypothesis. 37 BoNT-A reduces neurogenic CGRP and SP release, which can explain the subjective clinical observations of the disease. 38 In adult KC-Tie2 mice, intradermal injection of BoNT-A can significantly reduce skin lymphocytes compared with placebo Infiltrate and significantly improve acanthosis. 37 However, there are very few published clinical reports and observational studies, and none of them are placebo-controlled. Among 15 patients with inverse psoriasis, Zanchi et al.38 reported a good response to BoNT-A treatment; however, the results of patient self-assessment and infiltration photography assessment and erythema assessment were used. Therefore, Chroni et al39 pointed out various concerns about the study, including the lack of quantitative indicators to estimate improvements (such as PA scores). The author hypothesized that BoNT-A has a good effect in reducing local sweating in folds, such as Hailey-Hailey disease, where the effect of BoNT-A is due to the reduction of sweating. 40-42 The ability of BoNT-A to prevent hyperalgesia However, the release of neuropeptides leads to less pain and itching in patients. 43
Off-label, BoNT has been used to treat various bullous skin diseases, such as linear IgA bullous skin disease, Weber-Cockayne disease and Hailey-Hailey disease. BoNT-A injections, oral tacrolimus, yttrium aluminum garnet ablation laser, and BoNT-A containing erbium have been used to treat Hailey-Hailey disease in the sub-breast, axillary, inguinal and intergluteal cleft areas. After treatment, the clinical symptoms have improved, and the dose range is 25 to 200 U every 3 to 6 months. 42,44 In the reported case, a middle-aged woman with regional epidermolysis bullosa was injected 50 U per armpit into her foot, and 100 U was injected into a patient with linear IgA bullosa Foot of young patient with skin disease. 45,46
In 2007, Kontochristopoulos et al47 effectively treated the submammary area of ​​a 59-year-old patient, using BoNT-A as an adjuvant treatment for Darier’s disease for the first time. In another case in 2008, a young child with severe anogenital involvement was beneficial in reducing sweating at the abraded area. 48 Her concomitant infection was treated with 10 mg acitretin and antibiotics and antifungal drugs per day, but her quality of life was low and her discomfort persisted. Three weeks after the injection of botulinum toxin, her symptoms and clinical lesions were significantly improved.
Eccrine nevus is a rare skin hamartoma characterized by an increase in the number of eccrine glands but no blood vessel development. Due to the last feature, eccrine nevus is different from other diseases such as angiomatous eccrine hamartoma. 49 Small sweating moles are most common on the forearms, with few skin problems, but there are localized areas of hyperhidrosis. 50 Surgical resection or topical medication are the most popular treatments, depending on the size of the coverage and the entity of hyperhidrosis. Honeyman et al51 documented a 12-year-old child with congenital small sweat nevi on the right wrist that was resistant to topical antiperspirants. Due to the size of the tumor and its anatomical location, surgical resection was excluded. Hyperhidrosis makes participating in social and intellectual activities challenging. The researchers chose to inject 5 U of BoNT-A at 0.5-1 cm intervals. The authors did not specify when the first response to BoNT-A treatment occurred, but they did say that after a year, they noticed that the number of sweats was significantly reduced to once a month, and the patient’s quality of life improved. Lera et al49 treated a patient with low quality of life and HDSS score of 3 on the forearm with small sweat naevi (HDSS) (severe). BoNT-A (100 IU) was reconstituted in 2.5 mL sterile saline solution containing 0.9% sodium chloride and injected into the trace iodine test area. After 48 hours, the patient noticed reduced sweating, with the best results in the third week. The HDDS score drops to 1. Due to recurrence of sweating, BoNT-A treatment was repeated nine months later. In the treatment of exocrine hemangioma hamartoma, BoNT-A injection therapy is useful. 52 Although this condition is rare, it is easy to see how important it is for these people to have viable treatment options.
Hidradenitis suppurativa (HS) is a chronic skin disease characterized by pain, scars, sinuses, fistulas, inflamed nodules, and appears in the body’s apocrine glands in the late stages. 53 The pathophysiology of the disease is unclear, and previously accepted assumptions about HS development are now being challenged. The occlusion of the hair follicle is critical to the symptoms of HS, although the mechanism that causes the occlusion is not clear. As a result of subsequent inflammation and a combination of congenital and adaptive immune dysfunction, HS can develop skin damage. 54 A study by Feito-Rodriguez et al.55 reported that BoNT-A successfully treated prepubertal HS in 6-year-old girls. The case report of Shi et al.56 observed that BoNT-A was successfully treated in the -3 HS stage of a 41-year-old female. A recent study by Grimstad et al.57 evaluated whether the intradermal injection of BoNT-B is effective for HS in 20 patients. The DLQI of the BoNT-B group increased from a median of 17 at baseline to 8 at 3 months, while the DLQI of the placebo group decreased from 13.5 to 11.
Notalgia paresthetica (NP) is a persistent sensory neuropathy that affects the interscapular area, especially the T2-T6 dermatome, with upper back itching and skin symptoms related to friction and scratching. BoNT-A may help treat local itching by blocking the release of substance P, a pain and itching mediator. 58 Weinfeld’s case report59 evaluated the efficacy of BoNT-A in two cases. Both were successfully treated with BoNT-A. A study by Perez-Perez et al.58 evaluated the efficacy of BoNT-A in 5 patients diagnosed with NP. After intradermal injection of BoNT, multiple effects were observed. No individual’s itching was completely relieved. The randomized controlled trial (RCT) of Maari et al60 evaluated the efficacy and safety of BoNT-A in patients with NP at the Canadian Dermatology Research Clinic from July 2010 to November 2011. The study failed to confirm the beneficial effects of BoNT-A. Intradermal injection at a dose of up to 200 U to reduce itching in patients with NP.
Pompholyx, also called hyperhidrosis eczema, is a recurrent vesicular bullous disease that affects the palms and soles of the feet. Although the pathophysiology of this condition is unclear, it is now considered a symptom of atopic dermatitis. 61 Wet work, sweating, and obstruction are the most common predisposing factors. 62 Wearing gloves or shoes can cause pain, burning, itching, and discomfort in patients; bacterial infections are common. Swartling et al61 found that patients with palm hyperhidrosis treated with BoNT-A improved hand eczema. In 2002, they published the results of a study involving ten patients with bilateral vesicular hand dermatitis; one hand received BoNT-A injection, and the other hand served as a control during follow-up. The treatment had good or excellent results in 7 out of 10 patients. Of the 6 patients, Wollina and Karamfilov63 used topical corticosteroids on both hands and injected 100 U of BoNT-A intracutaneously on the most severely affected hands. In the hand treatment of the combination therapy, the authors found that itching and blisters decreased rapidly. They attributed the efficacy of BoNT-A to impetigo due to its non-perspirant effect and inhibition of SP.
Finger vasospasm, also known as Raynaud’s syndrome, is challenging to treat and is usually resistant to first-line drugs such as bosentan, iloprost, phosphodiesterase inhibitors, nitrates, and calcium channel blockers Agent. Surgical procedures involving recovery and shutdown, such as sympathectomy, are invasive. The Raynaud’s phenomenon associated with primary and sclerosis has been successfully treated by injection of BoNT. 64,65 Investigators noted that 13 patients experienced rapid pain relief, and chronic ulcers healed within 60 days after receiving 50-100 U of BoNT. Injections were given to 19 patients with Raynaud’s phenomenon. 66 After six weeks, the fingertip temperature of the fingertips treated with BoNT increased significantly compared with the injection of normal saline, indicating that BoNT is beneficial for the treatment of Raynaud’s phenomenon-related vasospasm. 67 Currently, are there any standardized injection procedures used; according to one study, injections in the fingers, wrists, or distal metacarpal bones did not lead to significantly different clinical results, although they are effective in treating Raynaud’s phenomenon-related vasospasm. 68
50-100 U of BoNT-A per armpit, administered intradermally in a grid-like design, can be used to treat primary axillary hyperhidrosis. The clinical results are visible within a week and last for 3 to 10 months. Most patients are satisfied with their treatment. Patients should be informed that up to 5% of cases will experience modern compensatory sweating. 69,70 BoNT can also effectively treat palm and plantar hyperhidrosis (Figure 5A and B).
Figure 5 The high-level clinical image (A) shows a young college student with diffuse palm hyperhidrosis who is anxious about this disease and does not respond to medication. Similar patients who received botulinum toxin treatment demonstrated complete resolution of hyperhidrosis (B). (Technology: After confirmation by starch iodine test; 100 units, 2.5 mL intradermal BoNT-A was injected once per hand. A total of two similar courses of 15 days apart produced a significant response lasting 6 months).
Each finger has 2-3 injection positions, and the injections should be arranged in a grid with a distance of 1 cm. BoNT-A can be given to each hand in the range of 75-100 units and to each foot in the range of 100-200 units. The clinical results may take up to a week to become apparent, and may last for three to six months. Before starting treatment, patients should be informed of the potential side effects of BoNT injections in the palms and feet. After palm injection, the patient may report weakness. On the other hand, plantar injections may make walking difficult, especially if nerve blocks are performed before BoNT treatment. 71,72 Unfortunately, 20% of plantar hyperhidrosis patients do not respond to treatment after receiving BoNT injections. 72
In recent studies, BoNT has been used to treat hyperhidrosis in a new way. In one case, a male patient with a pressure ulcer received 100 U of BoNT-A injections into the gluteal cleft every 6-8 months to reduce sweat production and accompanying wound maceration; skin integrity was maintained For more than two years, there has been no clinical deterioration of the pressure injury. 73 Another study used 2250 U of BoNT-B to be injected into the occipital scalp, parietal scalp, forehead scalp and forehead, as well as the perioral and peri-eye areas in a strip pattern to treat postmenopausal craniofacial hyperhidrosis. The DLQI of patients receiving BoNT-B improved by 91% within three weeks after treatment, while the quality of life of patients receiving placebo decreased by 18%. 74 BoNT injection is effective in the treatment of salivation and Frey syndrome. Otolaryngologists often perform treatment due to the anatomical location of the injection. 75,76
Colored sweat can be a clearly disturbing condition for the patient. Although this disease is very rare; involvement of the face and armpits can aggravate the patient’s dilemma. Many case reports and publications indicate that BoNT-A is effective after being injected in just 7 days. 77-79
The unpleasant smell from armpit hyperhidrosis and body odor may be embarrassing or disgusting. This may even have a negative impact on the patient’s mental space and confidence. Recently, Wu et al. reported that after intradermal injection of BoNT-A, the stench in the armpits was almost completely eliminated. 80 In another contemporary prospective study; 62 adolescents with a dermatological diagnosis of primary underarm odor were recruited. 82.25% of patients felt that the stench was significantly reduced after BoNT-A was injected into the axillary area. 81
Meh is identified by single or multiple benign cystic lesions in middle-aged women, mainly located in the central facial area, with a long course of disease and seasonal fluctuations. Meh usually appears in sunny conditions and is associated with hyperhidrosis. Many researchers have observed abnormal results in these cases after injecting BoNT-A.82 around the lesion.
Post-herpetic neuralgia (PHN) is the most common neurological complication of herpes zoster infection, which is more common in people over 60 years of age. BoNT-A directly produces pan-inhibitory effects on local nerve endings and regulates microglia-astrocytic-neuronal crosstalk. Many studies have noticed that after receiving BoNT-A treatment, patients whose pain is reduced by at least 30% to 50% have significantly reduced sleep scores and quality of life. 83
Chronic simple lichen is described as excessive focal pruritus without any obvious cause. This can greatly debilitate the patient. Clinical dermatological examination revealed isolated erythema plaques, increased skin markings and epidermal exfoliation. A recent landmark study from Egypt shows that BoNT-A can safely and effectively treat chronic lichen simplex, hypertrophic lichen planus, lichen planus, burns, reverse psoriasis, and local intractability of post-herpetic neuralgia Pruritus. 84
Keloids are abnormal tissue scars that occur after injury. Keloids are genetically related, and many treatments have been tried, but the effect is limited. However, none of them is completely cured. Although intralesional corticosteroids are still the main treatment method, intralesional injection of BoNT-A has become an excellent alternative in recent days. BoNT-A can reduce the levels of TGF-β1 and CTGF, and ultimately weaken the differentiation of fibroblasts. A number of studies have proved the success of BoNT-A in the treatment of keloids. In fact, the case series of two keloid patients even reported a 100% response, and the patients were very satisfied with the use of intralesional BoNT-A injection. 85
Congenital thick onychomycosis is a rare genetic disease accompanied by plantar hyperkeratosis, nail hypertrophy and hyperhidrosis. Few researchers have concluded that BoNT-A injection can not only improve hyperhidrosis, but also reduce pain and discomfort. 86,87
Water-borne keratosis is an uncommon disease. When the patient comes into contact with water, thickened white pebbles on the soles and palms of the hands and itching may occur. Several case reports in the literature show successful treatment and improvement after BoNT-A treatment, even in resistant cases. 88
Bleeding, edema, erythema and pain at the injection site may all be side effects of BoNT. 89 These side effects can be prevented by using a thinner needle and diluting BoNT with saline. BoNT injections can cause headaches; however, they usually disappear after 2-4 weeks. Systemic analgesics can be used to address this side effect. 90,91 Nausea, malaise, flu-like symptoms and ptosis are some other recorded side effects. 89 Ptosis is the side effect area of ​​using BoNT to treat the eyebrows. It is caused by local BoNT diffusion. This diffusion may last for several weeks, but it can be resolved with alpha-adrenergic agonist eye drops. When BoNT is injected into the lower eyelid, it can cause ectropion due to the local diffusion process. In addition, patients who receive BoNT injections to cure crow’s feet or rabbit patterns (periorbital) may develop strabismus due to inadvertent BoNT injection and local BoNT spread. 89,92 Nevertheless, as the paralytic effect of toxins gradually disappears, all these side effects will gradually disappear. 93,94
The risk of complications from cosmetic BoNT injections is low. Ecchymosis and purpura are the most common consequences and can be reduced by applying cold compresses to the injection site before and after the BoNT injection. 90,91 BoNT should be injected in a low dose, at least 1 cm from the edge of the orbital bone inferior, superior or lateral, with an appropriate dose. The patient should not manipulate the injection area within 2-3 hours after treatment, and sit or stand upright within 3-4 hours after treatment. 95
BoNT-A in various new formulations is currently being tested to treat glabellar lines and eye lines. The topical and injectable daxibotulinumtoxinA have been studied, but topical formulations have been shown to be ineffective. The injection DAXI has entered the FDA’s phase III trial, proving that the efficacy and clinical results in the treatment of glabellar lines may be up to 5 weeks longer than onabotulinumtoxinA. 96 LetibotulinumtoxinA is now on the market in Asia and has been approved by the FDA for the treatment of periorbital wrinkles. 97 Compared with incobotulinumtoxinA, LetibotulinumtoxinA has a higher concentration of neurotoxic protein per unit volume, but the amount of inactive neurotoxin is also higher, which increases the risk of immune response. 98
In addition to the new BoNT-A formulation, liquid BoNT-E is being studied because it is said to have a faster onset of action and a shorter duration of clinical results (14-30 days). EB-001 has been found to be safe and effective in reducing the appearance of frown lines and improving the appearance of forehead scars after Mohs microsurgery. 99 Dermatologists may be allowed to use these books. In addition to current aesthetic purposes, pharmaceutical companies are seeking BoNT-A preparations for off-label treatment of medical conditions of skin diseases.
BoNT is a highly adaptable injectable drug that can be used to treat a variety of skin diseases, including hidradenitis suppurativa, psoriasis, bullous skin disease, abnormal scars, hair loss, hyperhidrosis, and keloids. In cosmetic applications, BoNT is believed to be safe and effective in reducing facial wrinkles, especially the top third of the facial wrinkles. BoNT A is known for its use in reducing wrinkles in the cosmetics field. Although BoNT is generally safe, it is always important to understand the injection site because toxins may spread and negatively affect areas that should not be treated. Clinicians should be aware of complications in specific areas when injecting BoNT into the feet, hands, or neck. Dermatologists need to be familiar with the on-label and off-label uses of BoNT in order to provide patients with relevant treatments and reduce related morbidity. The clinical efficacy of BoNT in off-label settings and any potential long-term safety issues should be evaluated through well-designed clinical trials.
Data sharing does not apply to this article because no data sets were generated or analyzed during the current research period.
The examination of patients is carried out in accordance with the principles of the Declaration of Helsinki. The author certifies that she has obtained all appropriate patient consent forms in which the patient agrees to include images and other clinical information in the journal. Patients understand that their names and initials will not be made public, and will try to conceal their identities.
Dr. Piyu Parth Naik only contributed to the writing of the manuscript. The author has made significant contributions in concept and design, data acquisition and data interpretation; participated in drafting articles or critically revised important knowledge content; agreed to submit to the current journal; finally approved the version to be published; and agreed to the work Responsible for all aspects.