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Botulinum Toxin Type A
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Botulinum neurotoxin A (BoNT-A) which is generally known as anti-contraction of muscles has been reported as a successful treatment in various types of chronic ulcers.

BoNT-A ischemia neuromodulators
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Subjects: Cell Biology
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Revisions: 3 times (View History)
Update Date: 22 Jun 2022
Table of Contents

    1. Introduction

    Normal physiologic wound healing happens in three highly integrated and overlapping phases: inflammation, proliferation, and remodeling [1][2][3]. Good blood circulation, proper immune function, and adequate nutrition are required for optimum healing [1][4]. When any phase is disrupted, healing might be impeded and turned into chronic ulcers which are generally known as loss of normal skin integrity for more than 6 weeks [5][6][7]. Many factors attribute to retard wound healing. For instance, vascular insufficiency, neurologic abnormalities, nutritional deficiencies, advanced age, chronic diseases, and local wound infection can all disrupt the healing process [1][8][9][10]. Not only removing primary underlying causes but also following principles of wound care such as appropriate tissue debridement and optimal moist environment for normalization of the wound healing process is essential [1][11][12]. However, unsatisfied outcomes still exist [6][13][14].
    Botulinum toxin is a neurotoxin produced by Clostridium botulinum [15]. It has long been known for its action in preventing the release of the neurotransmitter acetylcholine from axons at the neuromuscular junction and temporally inhibiting muscle contraction. So far, there are seven serotypes (A, B, C1, D, E, F, and G) [16]. Serotypes A and B are currently in clinical usage, but botulinum neurotoxin A (BoNT-A) is the most commonly used [15][16]. Concerning temporary muscle paralysis capability, wide clinical treatment has been adopted [16][17][18]. Apart from inhibiting acetylcholine release from a presynaptic neuromuscular junction, studies found that BoNT-A can reduce skin inflammation by inhibiting mast cell degranulation and blocking cholinergic stimuli to apocrine and eccrine glands [19].

    2. Mechanism of BoNT-A on Wound Healing

    Normal physiologic wound healing is a dynamic process consisting of different continuous, overlapping, and precisely programmed phases [1][3][11]. Any disruption in the process leads to abnormal wound healing or chronic unhealed ulcers [12]. The literature review found BoNT-A can enhance wound healing in various types of ulcers. Several studies that investigated mechanisms of BoNT-A on wound healing found that BoNT-A decreased inflammatory cell infiltration during the inflammatory phase [20][21][22]. Inhibition of mast cell degranulation and reduction in number were reported [19][23]. Reduction in vascular permeability and exudation of neutrophils and macrophages were also observed. Consequently, pus deposition on ulcers was reduced [24]. Furthermore, during the proliferative phase, it could enhance blood flow and promote vascular sprouting by increasing expression in CD31+, ∝SAM (+) pericytes, as well as fibroblasts [25][26][27][28]. It could be due to a reduction of reactive oxygen species (ROS) release and endothelial nitric oxide synthase (eNOS) in the hypoxic area [25][29]. Altogether, granulation tissue was created and filled the wound. It also can inhibit releasing norepinephrine resulting in vasodilatation and increasing oxygenation to the wound [30]. In the period of the remodeling phase, lower expression of TGF-β1 by BoNT-A was found which reduces the risk of fibrosis and scar formation [24]. Figure 1 shows a mechanism of BoNT-A in wound healing for comprehensive understanding.
    Figure 1. The proposed mechanisms of botulinum neurotoxin A in the wound healing process. TGFβ-1: Transforming Growth Factor β-1.
    For miscellaneous types of chronic ulcers, BoNT-A has been proposed to hasten wound healing by inhibiting sweat-induced maceration of the fragile epidermis to optimize the wound environment [31].

    3. BoNT-A for Various Types of Skin Ulcers

    Ischemic Ulcers Secondary to Raynaud’s Phenomenon (RP)

    Although numerous publications demonstrated a positive effect of BoNT-A on RP [32][33][34][35][36], this entry will mainly focus on patients who had RP-associated ulcers. Based on the literature search, 12 articles (case reports, retrospective case series, and prospective case series) with a total of 104 patients who had RP-associated ulcers were identified (Table 1) [37][38][39][40][41][42][43][44][45][46][47][48]. Patients have been suffering from RP symptoms (pain, loss of function, disfigurement, and so forth) and chronic ischemic nonhealing ulcers. Moreover, some underwent sympathectomy but the clinical of ulcers did not improve [37].
    Table 1. A summary of articles on the treatment outcome of chronic ischemic ulcers secondary to Raynaud’s phenomenon.
    Abbreviations: MRA; Magnetic resonance angiography, NR; Not reported, NSS; Normal saline, PSV; Peak systolic velocity, SD; Standard deviation, VAS; Visual analog scale.
    There were seven studies that reported the type of BoNT-A used [38][39][42][44][45][46][48]. Onabotulinum toxin (Botox®, Allergan Pharmaceuticals Ltd., Westport, Ireland) was identified in five studies [38][39][42][45][46] and Medytoxin® (Medytox, Seoul, Korea) was used in two studies [44][48]. Regarding onabotulinum toxin, a minimum dose was 10 units, and a maximum dose was 77 units per one affected area [39][42]. Two reports from Korea used Medytoxin® with the same dose of 10 units [44][48]. Other articles did not mention the type of BoNT-A or toxin brand with the dose of 32–100 units per 1 affected area [37][40][41][43][47]. In terms of reconstitution, most common reconstitution adopted was toxin 20 units to 0.9% NSS 1 mL [41][42][45][49]. Two reports from Korea used BoNT-A 100 units to 0.9% NSS 1 mL [44][48]. The toxin concentration of other studies was BoNT-A 50 units to 0.9% NSS 1 mL [37][39] and BoNT-A 5 units to 0.9% NSS 1 mL [46], respectively.
    There was no standard guideline regarding the site of injection. Nevertheless, three areas of injection were proposed to target neurovascular bundles on palms: (1) Base of digits at web spaces (i.e., bifurcation of the superficial digital arteries) [37][38][39][45][47]; (2) Palmar aspect of the hand, just proximal to the A1 pulley, targeting the neurovascular bundles [37][42][46]; and (3) Both sides of proximal hand (i.e., radial and ulnar arteries) [38][39]. Most studies adopted either option 1 or 2 or a combination [37][42][45][46][47]. Two retrospective studies injected all three areas [38][39]. Injection patterns are shown in Figure 2. There were two reports with foot ulcers injected at interdigital web space oriented toward the neurovascular bundle [40][41].
    Figure 2. The BoNT-A injection patterns for Raynaud’s phenomenon-associated ulcer. Red dots represent the base of the digit injection pattern. Blue dots identify the palmar injection pattern. Purple dots identify the proximal hand injection pattern.
    Parameters tracked outcomes consisted of objective and subjective measurements. Among objective measurements, arterial blood flow was evaluated by using ultrasonography or doppler perfusion imaging, while skin surface temperature was assessed by a thermometer or temperature recovery after ice-bath immersion [42]. In terms of subjective assessment, a visual analog scale (VAS) for pain, general RP symptoms using Raynaud’s score [50], digital color changes, and patient global assessment were used. However, for healing ulcers, no wound assessment scale was used. Investigators merely monitored ulcers as complete, partial healing, and no response.
    Of a total of 104 cases with RP-associated ulcers, 81% (84 of104 cases) had healed completely. Immediate improvement of blood flow, pain, temperature, and color after injection was noted [37][41]. Raynaud’s score and VAS for pain decreased at 2 weeks and persisted until 16 weeks after injection [42].
    One case report presented a 55-year-old woman who was diagnosed with limited cutaneous systemic sclerosis with refractory multiple digital ulcers. She failed many medical treatment regimens and underwent amputation once. During the period of critical ischemic digits which further amputation was nearly executed, BoNT-A was challenged, and digits were rescued with complete wound healing eventually [43]. Another case report showed a 48-year-old male who was diagnosed with anti-MDA5-Ab-positive dermatomyositis with refractory digital ulcers had an improvement in ulcers after BoNT-A injection [44].
    According to a 3-year follow-up study by Medina et al., 8 of 14 patients (57.1%) demonstrated a very good response at 1 month after treatment. A mild to moderate response was observed in three patients (21.4%). Of the seven patients with basal ulcers, five were completely healed at 3 months after treatment. At the end of treatment, 64.3% of patients showed an overall satisfaction level of >8 [45].
    However, some patients with RP showed no response to BoNT-A injection which resulted in amputation. Therefore, the discussion with patients before employing this technique is mandatory [39][45][46].

    BoNT-A for Pressure Ulcers

    Administration of BoNT-A on pressure ulcers that were associated with muscle spasticity has been reported [51][52][53][54][55]. The rationale for the use of BoNT-A on pressure ulcers is to relieve muscle spasticity [56][57]. As a result, pressure ulcers are adequately accessed and omitted from repetitive trauma.

    Regarding the point of injection, BoNT-A can be injected directly into abnormally contracted muscle or under electromyographic guidance [52][53][54]. The number of injection points was considered based on the size of muscles. According to a report by Insito et al., abobotulinum toxin with doses of 200 and 120 speywood unit (SU) was injected into orbicularis oris and masseter in a vegetative state patient with oromandibular dyskinesia [54]. Regarding the larger size of muscles such as Gluteal muscle, a high dosage of 660 SU was used [53]. Gupta and Wilson reported a dosage of onabotulinum toxin ranging from 100 to 150 units per muscle [52]. Abnormal contraction or spasticity were improved as early as 1 week after treatment [5]. All ulcers were reported as complete healing with the most delayed time period of 6-month follow-up [53]. The number of treatment sessions varied from one to two sessions. A repeated treatment session might be considered in patients with partially healed ulcers to maintain the weakness of muscles. Data regarding the use of BoNT-A in pressure ulcers is summarized in Table 2.

    Table 2. A summary of articles on the treatment outcome of other types of chronic ulcer.

    Authors, Year

    Study Type

    N (Gender)

    Age, Years (Mean or Range)

    Type of BoNT-A

    BoNT-A Dilution with 0.9% NSS

    BoNT-A Dose/Location

    Follow-up Period

    Results

    Reinjection (Interval)

    Comments

    Gupta and Wilson, 2020 [52]

    Case report

    1 (female)

    59

    NR

    NR

    150 units for pectoralis major, 150 for elbow flexors, 100 for flexor digitorum superficialis

    5 months

    Completely healed ulcer

    Yes

    (5 months)

    Pressure ulcer

    Insito and Basciani, 2009 [53]

    Case report

    1 (male)

    27

    Dysport®, Ipsen Limited, Slough, UK

    NR

    660 Speywood units  (left Gluteus maximus)

    6 months

    Weaken muscle contraction

    Healed ulcer

    Yes

    (3 months)

    Pressure ulcer

    Insito et al., 2008 [54]

    Case report

    1 (male)

    73

    Dysport®, Ipsen Limited, Slough, UK

    NR

    200 Speywood units for Orbicularis oris, 120 for Masseter

    3 months

    Improved dyskinetic disorder

    Completely healed ulcer

    Yes

    (2 months)

    Pressure ulcer

    Sillitoe et al., 2007 [55]

    Letter to editors

    1 (male)

    58

    NR

    NR

    NR (adductor muscle bellies lower limbs)

    16 weeks

    Marked reduction in spasticity

    Ulcers showed signs of healing

    Ulcers show significant improvement

    Ulcers fully healed

    No

    Pressure ulcer

    Laarakker and Borah, 2020 [58]

    Retrospective cohort, case series

    5 (NR)

    31-71

    NR

    NR

    80–100 units (palm and wrist)

    NR

    All Digits were preserved

    No

    Traumatic ulcer

    Upton et al., 2009 [59]

    Letter to editors

    1 (NR)

    4

    NR

    NR

    10 units (palm)

    NR

    The digits were rescued

    No

    Traumatic ulcer

    Zhong et al., 2019 [60]

    Case series

    4 (female 1/male 3)

    16-78

    NR

    NR

    32–48 units (face, leg, foot)

    50 days

    Ulcers healed

    No

    Chronic skin ulcer

     

    Alsharqi et al., 2011 [61]

    Correspondence

    1 (male)

    51

    Botox® (Allergan Pharmaceuticals Ltd., Westport, Ireland)

    NR

    70 units (right foot)

    3 months

    Completely healed ulcer

    Yes (3 months)

    Neuropathic ulcer

    Abbreviation: NR; Not reported, NSS; Normal saline.

    BoNT-A for Traumatic Ulcers

    Posttraumatic ulcers associated with vascular compromise (e.g., crush, direct drug injection, proximal arterial injury from catheterization, etc.) were reported successfully treated by BoNT-A [58][59]. According to a retrospective cohort study by Laarakker et al., patients with traumatic ischemic ulcers were categorized into two groups (BoNT-A treated group vs. non-BoNT-A group). In the BoNT-A treated group, 80 to 100 units of onabotulinum toxin were injected into the palm of each patient. The location of injection was at the level of the distal palmar crease and close to the radial and ulnar arteries. All digits (100%) were rescued for the BoNT-A injection group, while 83% had amputation of necrotic digits in patients without BoNT-A injection [58]. In addition, pain scores were lower in BoNT-A-treated fingers when compared to no BoNT-A injection. The postulated mechanism was the improvement of blood flow by BoNT-A. Another traumatic ulcer on the hand of a 4-year-old child was rescued without amputation by administration of 10 units BoNT-A into the proximal palm, the radial and ulnar artery locations of the distal forearm [59]. Data regarding the use of BoNT-A for traumatic ulcers is summarized in Table 2.

    BoNT-A for Other Types of Chronic Ulcers

    Neuropathic foot ulcer has been reported to be successfully treated by two sessions of BoNT-A injection [61]. The amount of 70 units of onabotulinum toxin was infiltrated around the ulcer with a repeated injection at 3 months with a similar dosage. The proposed mechanism was a reduction of sweat-induced maceration and optimization of the wound-healing environment.

    Zhong et al. reported various types of chronic ulcers that have been successfully treated by BoNT-A administration in four patients [60]. One interesting case was a chronic infective skin ulcer on the left temporal region due to acne squeezing. After systemic antibiotics and debridement, there was a slight improvement in the ulcer. Multiple points of BoNT-A injection around the ulcer were done with 32 units in total. The wound was completely healed 20 days after injection. Data regarding the use of BoNT-A for other types of chronic ulcers is summarized in Table 2.

    4. Practical Guidelines for Treatment

    To date, a standard guideline for BoNT-A injection for chronic ulcers has not been established yet due to a lack of strong evidence that supports the efficacy of BoNT-A for skin ulcers. Based on the available data, BoNT-A might be offered to patients with chronic skin ulcers due to vascular compromised (i.e., RP-associated ulcer, pressure ulcers with vascular compromised), traumatic ulcers, etc. (Figure 3). BoNT-A for RP-associated ulcers seems to be the most promising efficacy and established treatment method. Nevertheless, its harmlessness and ubiquity make it worth trying for those chronic ulcers that failed standard therapy. Adverse effects were mild and temporally, an intrinsic hand muscle weakness has been reported which resolved completely within 5 months [41][43][49][50]. In terms of point of injection, the recommendation is to consider the type of ulcer including 1) ischemic ulcers: inject toward neurovascular bundles for vasodilation [41][42][43][46][49][50][51]; 2) pressure ulcers: inject into contracted and spastic muscles for muscle relaxation; and 3) other types: inject around the ulcer to optimize wound environment [60][61]. Dosage and reconstitution should be considered individually depending on wound size or volume of muscle.

    Toxins 14 00406 g003

    Figure 3. Potential role of BoNT-A for various types of chronic ulcers.

    5. Conclusions

    In summary, BoNT-A injection, a minimally invasive procedure that has a low rate of side effects can be adjunctive therapy for enhancing wound healing in various types of chronic ulcers that have been treated for underlying causes and had wound care properly as well as in ischemic ulcers associated RP in which failed conventional therapy. However, there is no randomized controlled trial study (RCT) with a large number of patients to affirm those efficacies. The amount of BoNT-A injection and the exact point of injection is still uncertain. Future randomized controlled studies should be conducted to evaluate the efficacy and safety of BoNT-A for various types of ulcers with different anatomical regions.

    References

    1. Fonder, M.A.; Lazarus, G.S.; Cowan, D.A.; Aronson-Cook, B.; Kohli, A.R.; Mamelak, A.J. Treating the chronic wound: A practical approach to the care of nonhealing wounds and wound care dressings. J. Am. Acad. Dermatol. 2008, 58, 185–206.
    2. Singer, A.J.; Clark, R.A. Cutaneous wound healing. N. Engl. J. Med. 1999, 341, 738–746.
    3. Baum, C.L.; Arpey, C.J. Normal cutaneous wound healing: Clinical correlation with cellular and molecular events. Dermatol. Surg. 2005, 31, 674–686.
    4. Goldman, R. Growth factors and chronic wound healing: Past, present, and future. Adv. Skin Wound Care 2004, 17, 24–35.
    5. Singh, A.; Halder, S.; Menon, G.R.; Chumber, S.; Misra, M.C.; Sharma, L.K.; Srivastava, A. Meta-analysis of randomized controlled trials on hydrocolloid occlusive dressing versus conventional gauze dressing in the healing of chronic wounds. Asian J. Surg. 2004, 27, 326–332.
    6. Martinengo, L.; Olsson, M.; Bajpai, R.; Soljak, M.; Upton, Z.; Schmidtchen, A.; Car, J.; Järbrink, K. Prevalence of chronic wounds in the general population: Systematic review and meta-analysis of observational studies. Ann. Epidemiol. 2019, 29, 8–15.
    7. Nussbaum, S.R.; Carter, M.J.; Fife, C.E.; DaVanzo, J.; Haught, R.; Nusgart, M.; Cartwright, D. An Economic Evaluation of the Impact, Cost, and Medicare Policy Implications of Chronic Nonhealing Wounds. Value Health 2018, 21, 27–32.
    8. Nelzen, O.; Bergqvist, D.; Lindhagen, A. Venous and non-venous leg ulcers: Clinical history and appearance in a population study. Br. J. Surg. 1994, 81, 182–187.
    9. Singh, N.; Armstrong, D.G.; Lipsky, B.A. Preventing foot ulcers in patients with diabetes. JAMA 2005, 293, 217–228.
    10. Brem, H.; Sheehan, P.; Rosenberg, H.J.; Schneider, J.S.; Boulton, A.J. Evidence-based protocol for diabetic foot ulcers. Plast. Reconstr. Surg. 2006, 117, 193S–209S.
    11. Powers, J.G.; Higham, C.; Broussard, K.; Phillips, T.J. Wound healing and treating wounds: Chronic wound care and management. J. Am. Acad. Dermatol. 2016, 74, 607–625.
    12. Morton, L.M.; Phillips, T.J. Wound healing and treating wounds: Differential diagnosis and evaluation of chronic wounds. J. Am. Acad. Dermatol. 2016, 74, 589–605.
    13. Bickers, D.R.; Lim, H.W.; Margolis, D.; Weinstock, M.A.; Goodman, C.; Faulkner, E.; Gould, C.; Gemmen, E.; Dall, T. The burden of skin diseases: 2004 a joint project of the American Academy of Dermatology Association and the Society for Investigative Dermatology. J. Am. Acad. Dermatol. 2006, 55, 490–500.
    14. Olsson, M.; Jarbrink, K.; Divakar, U.; Bajpai, R.; Upton, Z.; Schmidtchen, A.; Car, J. The humanistic and economic burden of chronic wounds: A systematic review. Wound Repair Regen. 2019, 27, 114–125.
    15. Erbguth, F.J. From poison to remedy: The chequered history of botulinum toxin. J. Neural Transm. (Vienna) 2008, 115, 559–565.
    16. Alster, T.S.; Harrison, I.S. Alternative Clinical Indications of Botulinum Toxin. Am. J. Clin. Dermatol. 2020, 21, 855–880.
    17. Campanati, A.; Martina, E.; Giuliodori, K.; Consales, V.; Bobyr, I.; Offidani, A. Botulinum Toxin Off-Label Use in Dermatology: A Review. Skin Appendage Disord. 2017, 3, 39–56.
    18. Lewandowski, M.; Świerczewska, Z.; Barańska-Rybak, W. Off-Label Use of Botulinum Toxin in Dermatology-Current State of the Art. Molecules 2022, 27, 3143.
    19. Choi, J.E.; Werbel, T.; Wang, Z.; Wu, C.C.; Yaksh, T.L.; Di Nardo, A. Botulinum toxin blocks mast cells and prevents rosacea like inflammation. J. Dermatol. Sci. 2019, 93, 58–64.
    20. Al-Qattan, M.M.; Al-Shanawani, B.N.; Alshomer, F. Botulinum toxin type A: Implications in wound healing, facial cutaneous scarring, and cleft lip repair. Ann. Saudi Med. 2013, 33, 482–488.
    21. Chang, C.S.; Wallace, C.G.; Hsiao, Y.C.; Chang, C.J.; Chen, P.K. Botulinum toxin to improve results in cleft lip repair: A double-blinded, randomized, vehicle-controlled clinical trial. PLoS ONE 2014, 9, e115690.
    22. Gassner, H.G.; Sherris, D.A.; Otley, C.C. Treatment of facial wounds with botulinum toxin A improves cosmetic outcome in primates. Plast. Reconstr. Surg. 2000, 105, 1948–1953.
    23. Park, T.H. The effects of botulinum toxin A on mast cell activity: Preliminary results. Burns 2013, 39, 816–817.
    24. Lee, B.J.; Jeong, J.H.; Wang, S.G.; Lee, J.C.; Goh, E.K.; Kim, H.W. Effect of botulinum toxin type a on a rat surgical wound model. Clin. Exp. Otorhinolaryngol. 2009, 2, 20–27.
    25. Uchiyama, A.; Yamada, K.; Perera, B.; Ogino, S.; Yokoyama, Y.; Takeuchi, Y.; Ishikawa, O.; Motegi, S. Protective effect of botulinum toxin A after cutaneous ischemia-reperfusion injury. Sci. Rep. 2015, 5, 9072.
    26. Kim, Y.S.; Roh, T.S.; Lee, W.J.; Yoo, W.M.; Tark, K.C. The effect of botulinum toxin A on skin flap survival in rats. Wound Repair Regen. 2009, 17, 411–417.
    27. Liu, H.; Yu, Z.; Wang, J.; Zhang, X.; Lei, L.; Zhang, Y.; Su, Y.; Ma, X. Effects of Botulinum Toxin A on the Blood Flow in Expanded Rat Skin. J. Investig. Surg. 2022, 35, 1036–1043.
    28. Park, T.H.; Rah, D.K.; Chong, Y.; Kim, J.K. The effects of botulinum toxin A on survival of rat TRAM flap with vertical midline scar. Ann. Plast. Surg. 2015, 74, 100–106.
    29. Schweizer, D.F.; Schweizer, R.; Zhang, S.; Kamat, P.; Contaldo, C.; Rieben, R.; Eberli, D.; Giovanoli, P.; Erni, D.; Plock, J.A. Botulinum toxin A and B raise blood flow and increase survival of critically ischemic skin flaps. J. Surg. Res. 2013, 184, 1205–1213.
    30. Morris, J.L.; Jobling, P.; Gibbins, I.L. Botulinum neurotoxin A attenuates release of norepinephrine but not NPY from vasoconstrictor neurons. Am. J. Physiol. Heart Circ. Physiol. 2002, 283, H2627–H2635.
    31. Swartling, C.; Karlqvist, M.; Hymnelius, K.; Weis, J.; Vahlquist, A. Botulinum toxin in the treatment of sweat-worsened foot problems in patients with epidermolysis bullosa simplex and pachyonychia congenita. Br. J. Dermatol. 2010, 163, 1072–1076.
    32. Segreto, F.; Marangi, G.F.; Cerbone, V.; Persichetti, P. The Role of Botulinum Toxin A in the Treatment of Raynaud Phenomenon. Ann. Plast. Surg. 2016, 77, 318–323.
    33. Shwe, S.; Sharma, A.A.; Chahal, H.S.; Doan, L.T.; Rojek, N.W. Botulinum Toxin for the Treatment of Intractable Raynaud Phenomenon. Cutis 2021, 108, E11–E14.
    34. Ennis, D.; Ahmad, Z.; Anderson, M.A.; Johnson, S.R. Botulinum toxin in the management of primary and secondary Raynaud’s phenomenon. Best Pract. Res. Clin. Rheumatol. 2021, 35, 101684.
    35. Bello, R.J.; Cooney, C.M.; Melamed, E.; Follmar, K.; Yenokyan, G.; Leatherman, G.; Shah, A.A.; Wigley, F.M.; Hummers, L.K.; Lifchez, S.D. The Therapeutic Efficacy of Botulinum Toxin in Treating Scleroderma-Associated Raynaud’s Phenomenon: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Arthritis Rheumatol. 2017, 69, 1661–1669.
    36. Uppal, L.; Dhaliwal, K.; Butler, P.E. A prospective study of the use of botulinum toxin injections in the treatment of Raynaud’s syndrome associated with scleroderma. J. Hand Surg. Eur. Vol. 2014, 39, 876–880.
    37. Smith, L.; Polsky, D.; Franks, A.G., Jr. Botulinum toxin-A for the treatment of Raynaud syndrome. Arch. Dermatol. 2012, 148, 426–428.
    38. Zhang, X.; Hu, Y.; Nie, Z.; Song, Y.; Pan, Y.; Liu, Y.; Jin, L. Treatment of Raynaud’s phenomenon with botulinum toxin type A. Neurol. Sci. 2015, 36, 1225–1231.
    39. Fregene, A.; Ditmars, D.; Siddiqui, A. Botulinum toxin type A: A treatment option for digital ischemia in patients with Raynaud’s phenomenon. J. Hand Surg. Am. 2009, 34, 446–452.
    40. Castanedo, L.Q.; Rodríguez, M.F.; Pedrero, R.M.; Fernández, C.C.; Laguna, R.d.L. Ischemic ulcers of the toes secondary to Raynaud’s phenomenon in a child successfully treated with botulinum toxin. Pediatr. Dermatol. 2020, 37, 681–683.
    41. Garrido-Ríos, A.A.; González-Olivares, M.; Navarro-Vidal, B.; Martínez-Morán, C.; Borbujo, J. Ischaemic ulcers on the toes secondary to Raynaud phenomenon in a patient with systemic sclerosis successfully treated with botulinum toxin. Clin. Exp. Dermatol. 2018, 43, 503–505.
    42. Motegi, S.; Yamada, K.; Toki, S.; Uchiyama, A.; Kubota, Y.; Nakamura, T.; Ishikawa, O. Beneficial effect of botulinum toxin A on Raynaud’s phenomenon in Japanese patients with systemic sclerosis: A prospective, case series study. J. Dermatol. 2016, 43, 56–62.
    43. Blaise, S.; Roustit, M.; Forli, A.; Imbert, B.; Cracowski, J.L. Non-healing ischaemic digital ulcer in a systemic sclerosis patient: A challenging clinical case. Int. Wound J. 2017, 14, 978–981.
    44. Min, H.K.; Kim, H.R.; Lee, S.H.; Park, S.H.; Oh, J.; Choi, K. Refractory Digital Ulcers Treated by Botulinum Toxin and Endothelin Receptor-1 Antagonist in Anti-MDA5-Antibody-Positive Dermatomyositis. J. Clin. Neurol. 2020, 16, 160–162.
    45. Medina, S.; Gómez-Zubiaur, A.; Valdeolivas-Casillas, N.; Polo-Rodríguez, I.; Ruíz, L.; Izquierdo, C.; Guirado, C.; Cabrera, A.; Trasobares, L. Botulinum toxin type A in the treatment of Raynaud’s phenomenon: A three-year follow-up study. Eur. J. Rheumatol. 2018, 5, 224–229.
    46. Neumeister, M.W. Botulinum toxin type A in the treatment of Raynaud’s phenomenon. J. Hand Surg. Am. 2010, 35, 2085–2092.
    47. Habib, S.M.; Brenninkmeijer, E.E.A.; Vermeer, M.H.; de Vries-Bouwstra, J.K.; Velthuis, P.J. Botulinum toxin type A in the treatment of Raynaud’s phenomenon. Dermatol. Ther. 2020, 33, e14182.
    48. Souk, J.W.; Kim, H.S. Effects of botulinum toxin injection on systemic sclerosis-related digital ulcers. Korean J. Intern. Med. 2019, 34, 1169–1170.
    49. Zhong, J.; Lan, Y.; Fu, S.; Zhang, J.; Lu, S.; He, Y.; Zhang, J.M. Botulinum Toxin A Injection for Treatment of Chronic Skin Ulcer: A Case Series and Literature Review. Int. J. Low. Extrem. Wounds 2019, 18, 97–103.
    50. Merkel, P.A.; Herlyn, K.; Martin, R.W.; Anderson, J.J.; Mayes, M.D.; Bell, P.; Korn, J.H.; Simms, R.W.; Csuka, M.E.; Medsger, T.A., Jr.; et al. Measuring disease activity and functional status in patients with scleroderma and Raynaud’s phenomenon. Arthritis Rheum. 2002, 46, 2410–2420.
    51. Merkel, P.A.; Herlyn, K.; Martin, R.W.; Anderson, J.J.; Mayes, M.D.; Bell, P.; Korn, J.H.; Simms, R.W.; Csuka, M.E.; Medsger, T.A., Jr.; et al. Measuring disease activity and functional status in patients with scleroderma and Raynaud’s phenomenon. Arthritis Rheum. 2002, 46, 2410–2420.
    52. Gupta, A.D.; Wilson, D.H. Use of botulinum toxin to heal atypical pressure ulcers in the palm. Med. J. Aust. 2020, 212, 55–65.e1.
    53. Intiso, D.; Basciani, M. Botulinum toxin type A in the healing of a chronic buttock ulcer in a patient with spastic paraplegia after spinal cord injury. J. Rehabil. Med. 2009, 41, 1100–1102.
    54. Intiso, D.; Basciani, M.; Di Rienzo, F.; Tolfa, M.; Grimaldi, G.; Fiore, P. Botulinum toxin type A in the healing of ulcer following oro-mandibular dyskinesia in a patient in a vegetative state. J. Rehabil. Med. 2008, 40, 315–316.
    55. Sillitoe, A.T.; Bains, R.D.; Stanley, P.R.W. Botulinum toxin as a treatment for leg ulcers. Plast. Reconstr. Surg. 2007, 119, 1633.
    56. Turkel, C.C.; Bowen, B.; Liu, J.; Brin, M.F. Pooled analysis of the safety of botulinum toxin type A in the treatment of poststroke spasticity. Arch. Phys. Med. Rehabil. 2006, 87, 786–792.
    57. Bjornson, K.; Hays, R.; Graubert, C.; Price, R.; Won, F.; McLaughlin, J.F.; Cohen, M. Botulinum toxin for spasticity in children with cerebral palsy: A comprehensive evaluation. Pediatrics 2007, 120, 49–58.
    58. Laarakker, A.S.; Borah, G. Botulinum Toxin A Salvage of Ischemic Hand Trauma. Plast. Reconstr. Surg. 2020, 145, 161–164.
    59. Upton, J.; Garcia, J.; Liao, E. Botox to the rescue. Plast. Reconstr. Surg. 2009, 123, 38e.
    60. Zhong, J.; Lan, Y.; Fu, S.; Zhang, J.; Lu, S.; He, Y.; Zhang, J.M. Botulinum Toxin A Injection for Treatment of Chronic Skin Ulcer: A Case Series and Literature Review. Int. J. Low. Extrem. Wounds 2019, 18, 97–103.
    61. Alsharqi, A.; Curley, R.; Winhoven, S. Botulinum toxin type A in the management of a neuropathic foot ulcer. Clin. Exp. Dermatol. 2011, 36, 915–916.
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      Winayanuwattikun, W.; Vachiramon, V. Botulinum Toxin Type A. Encyclopedia. Available online: https://encyclopedia.pub/entry/24228 (accessed on 07 February 2023).
      Winayanuwattikun W, Vachiramon V. Botulinum Toxin Type A. Encyclopedia. Available at: https://encyclopedia.pub/entry/24228. Accessed February 07, 2023.
      Winayanuwattikun, Waranaree, Vasanop Vachiramon. "Botulinum Toxin Type A," Encyclopedia, https://encyclopedia.pub/entry/24228 (accessed February 07, 2023).
      Winayanuwattikun, W., & Vachiramon, V. (2022, June 20). Botulinum Toxin Type A. In Encyclopedia. https://encyclopedia.pub/entry/24228
      Winayanuwattikun, Waranaree and Vasanop Vachiramon. ''Botulinum Toxin Type A.'' Encyclopedia. Web. 20 June, 2022.
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