Botulinum Neurotoxin Type A in the Treatment of Facial Seborrhea and Acne

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Intradermal injection of botulinum neurotoxin is a frequently performed procedure in aesthetic dermatology to improve facial skin tone, texture, fine wrinkles, and enlarged pores. In practice, botulinum neurotoxin type A is also used to reduce skin oiliness of the face. There is increasing evidence that acetylcholine plays specific roles in sebum production, suggesting that botulinum neurotoxin type A may reduce sebum production by interfering with cholinergic transmission between sebaceous glands and autonomic nerve terminals. Botulinum neurotoxins can also inhibit several pathogenetic components of acne development, suggesting that botulinum neurotoxins can be used as a safe and effective treatment modality for acne and other skin disorders related to overactivity of sebaceous glands. This review aims to explore the current evidence behind the treatment of facial seborrhea and acne with botulinum neurotoxin type A.

1. Introduction

A sebaceous gland (SG) is a microscopic exocrine gland in the skin that opens into a hair follicle to secrete an oily or waxy matter called sebum. Sebum production is physiologic and serves to lubricate the hairs and the stratum corneum. However, when produced in excess, it can be an aesthetic concern for many people since it frequently accompanies greasy skin and enlargement of facial pores (Figure 1). The consequences of excess sebum may be associated with adverse psychological and social effects resulting from skin oiliness and shine and prominent pores [1]. Facial seborrhea (“oily skin”), caused by an excessive sebum production in the facial skin, is also a major pathogenetic factor in several dermatologic disorders such as acne [2,3]. One of the most effective inhibitors of sebum production is oral isotretinoin. However, many patients cannot tolerate, are unwilling to accept the side effects, are contraindicated for its use, or do not have severe enough disease to justify its use [2]. The studies show that lasers and other energy-based treatments can reduce sebum production. However, a shorter duration of efficacy, potential side effects, and the relative lack of evidence are common drawbacks to these treatments.

Botulinum neurotoxin type A (BoNTA) blocks the release of acetylcholine (Ach) into the synaptic cleft, where it binds to a cholinergic receptor on a post-synaptic cell. Acting at the neuromuscular junction, BoNTA leads to a loss of muscle tone, while in some glandular tissues, it inhibits cholinergic sympathetic nerve function. The ability of BoNTA to inhibit cholinergic transmission prompted further investigations into its clinical use in several autonomic disorders resulting in glandular hypersecretion, such as hyperhidrosis and sialorrhea [1,2]. Another well-known cutaneous exocrine gland is the SG, opening into a hair follicle to secrete sebum. The neuronal control over the SG has long been implicated by clinical observations [4–7]. Empirical reports on the use of BoNTA to suppress excessive sebum suggest that BoNTA could modulate the neuroendocrine control over the SGs [8]. This review summarizes in vitro and in vivo studies relevant to BoNTA therapy for SG overactivity. We also reviewed the reported cases and clinical trials on the use of BoNTA for facial seborrhea, wide pores, and associated acne.

Botulinum Neurotoxin for Sebum Reduction

3.1. Anecdotal Clinical Reports
3.2. Extraneuronal Cholinergic System of Sebaceous Glands
3.3. Early Observations
3.4. OnabotulinumtoxinA
3.5. IncobotulinumtoxinA and AbobotulinumtoxinA
3.6. Enlarged Facial Pores
3.7. Limitations of the Procedure

4. Botulinum Neurotoxin for Acne Treatment: Possible Mechanisms
4.1. Pathogenesis of Acne
4.2. Acne and Cholinergic Signaling
4.3. Catecholamines
4.4. Mediators of Inflammation in Acne

5. Conclusions

BoNTA affects cholinergic transmission and other neurotransmitter pathways of SG activities. Data from in vitro and in vivo studies indicate that BoNTA can be a potential tool to treat facial seborrhea and acne, closely related to abnormal sebaceous gland activities (Figure 5). A review of clinical trials revealed that intradermal injection of BoNTA is an effective and safe treatment of excessive sebum secretion and prominent facial pores. Since BoNTA is not labeled for acne treatment, it should be kept as a secondary option in acne management until more clinical trials confirm these promising results. Further research is recommended to present more robust evidence for the functional role of BoNTA in SG biology.


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Figure 1. (a) A young Korean male with facial seborrhea appearing greasy and shiny, accompanied by enlarged pores on the cheeks; (b) Histologic findings of the facial skin of excess sebum secretion. Note the lobules of mature sebaceous glands and a dilated follicular infundibulum filled with keratinous material (nose, hematoxylin, and eosin staining, ×50.

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Figure 2. Increased lipid synthesis in cultured sebocytes after treatment with 10 nM of acetylcholine. Intracellular lipids are detected in acetylcholine-treated sebocytes by lipid staining (Photos are used with the kind permission of Dr. Myung Im, MD, IM Dermatology Clinic, Daejeon, Korea).
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Table 1. Quantitative studies on the effect of botulinum neurotoxins on sebum secretion in patients with facial seborrhea.
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Figure 3. Changes in sebum secretion relative to baseline at each follow-up point after injection of botulinum toxin type A into the forehead. ABO30: abobotulinumtoxinA 30 units; ABO45: abobotulinumtoxinA 45 units; ONA10: onabotulinumtoxinA 10 units; ONA20: onabotulinumtoxinA 20 units. The graph was plotted using the data from [32,34].
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Figure 4. A young Korean female with facial seborrhea and acne on the forehead. Two weeks after intradermal injection of 12 units of onabotulinumtoxinA, a significant improvement was observed.
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