The Potential Role of Botulinum Toxin in Improving Superficial Cutaneous Scarring: A Review
September 2018 | Volume 17 | Issue 9 | Original Article | 956 | Copyright © 2018
Akash Dhawan,a Sunil Dhawan MD,b,c Domenico Vitarella PhDd
aDepartment of Bioengineering, Rice University, Houston, TX bCenter for Dermatology Clinical Research, Inc., Fremont, CA cDepartment of Dermatology, Stanford University School of Medicine, Stanford, CA dBonti, Inc., Newport Beach, CA
Botulinum toxins have been utilized in a number of cosmetic and therapeutic applications. One of the more novel uses of botulinum toxin involves its use to mitigate the effects of superficial cutaneous scarring. This is accomplished by decreasing the dynamic tension of a wound by denervating the underlying muscle. Studies have indicated that botulinum toxin serotypes A and B have a positive effect on wound healing and scar appearance. However, larger prospective, blinded, randomized, placebo-controlled clinical trials are required to refine this concept and target optimum toxin dose placement, timing, and concentration. The delayed onset of effect of available botulinum toxins is likely not taking full advantage of the scar improvement capabilities of the toxin, considering the time to immobilization of the muscle is a key factor in the improvement of wound healing with this technique. Furthermore, it has been noted in studies that the use of botulinum toxin can result in significant, yet temporary functional issues, due to prolonged paralysis of the muscle. In this paper, we review the role of botulinum toxin in improving scar appearance, evaluate animal and human studies to date demonstrating its effect on scarring, and highlight an opportunity for continued research in this application. J Drugs Dermatol. 2018;17(9):956-958.
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The Clostridium botulinum bacteria secretes 8 different exotoxins, called serotypes A-H.1,2 Serotype A is the most potent and is marketed under the brand name Botox ® (Allergan, Inc., Irvine, CA). Serotype A consists of a 1295 amino acid chain with a 97 kDa heavy chain and a 57 kDA light chain.The binding domain on the heavy chain attaches to the receptor on the presynaptic terminal.The light and heavy chains are internal- ized via receptor mediated endocytosis into the endosome of the nerve terminal that contains the acetylcholine neurotransmitter. In the acidic environment of the endosome, the light chain can cross the membrane via translocation into the cytosol and acti- vate the metalloprotease enzymatic domain. This domain then disables the synaptosomal-associated protein 25 by cleaving 9 amino acids on the C-terminus. When this protein is cleaved, there is no vesicle-membrane fusion and no release of acetyl- choline in the synapse. This neural blockade results in flaccid pa- ralysis of the affected muscle.3,4 Scott et al (1980) first proposed the use of botulinum toxin in hu- mans to immobilize extraocular muscles as an alternate therapy for strabismus surgery.5 Carruthers et al (1992) determined that the toxin could be applied in cosmetic uses to correct for glabellar rhytids.6 Since then, botulinum toxin has been used to treat rhy- tids on other facial areas, including the forehead and periorbital area. Botulinum toxin injections are the most common cosmetic procedures in the United States with 4.6 million injections per- formed in 2016, exceeding other well-known procedures such as filler injections and blepharoplasty.7 This high rate of usage has led to its application in expanded indications such as hyperhi- drosis, migraines, and other possible novel uses.8,9 Among these novel uses, studies have shown that botulinum toxins may be used to mitigate the effects of superficial cutaneous scarring.10
Wound Repair and Scarring
Cosmetic results of wound repairs are dependent on many factors, including the quality of the closure, infection, and suture quality. A key factor is the tension on the wound edges, which tends to increase inflammation, leading to fibrosis and erythe- ma. Tension is composed of static tension (the result of wound location, size, closure techniques, etc.) and dynamic tension. Dynamic tension is caused by the action of the muscles underlying the wound. Specifically, the relaxed skin tension lines of Borges and Langer are perpendicular to the tension vectors of the un- derlying muscle, and wounds that are repaired parallel to these relaxed skin tension lines (RSTL) have less dynamic tension and heal with a better cosmetic result. Scars that are perpendicular to these RSTL have increased tension, which results in increased inflammation, increased deposition of collagen and glycos- aminoglycans, increased fibroblastic response, and poor wound healing and increased scarring.11 Decreasing dynamic tension by denervating the underlying muscle with botulinum toxin offers