and this may have an effect on the outcome. Sample sizes are
small, and no large, placebo-controlled trials have been conducted
In addition to flushing, hypersebaceous activity is characteristic
in many patients with rosacea, especially those with a
glandular type.3 Excess sebum production is also a frequently implicated
component of acne vulgaris. In a large meta-analysis of
patients treated with onabotulinumtoxinA for facial lines, acne
was statistically significantly less common in the onabotulinumtoxinA-
treated participants than in the placebo group,18
suggesting that onabotulinumtoxinA may have a therapeutic effect
on acne reduction. Although a mechanism of action has not
been clearly identified in explaining the botulinum toxin type A
effects on reducing acne, there is speculation that the neuropeptides
ACh and SP may be a neurogenic origin of both sebaceous
activity and inflammation.19 Moreover, botulinum toxin type A
at 2 U/0.1 cc dilution, a known inhibitor, has been reported to
reduce oily skin and the appearance of pore size when injected
intradermally into facial skin.20 Other studies have also indicated
that intradermal injections on onabotulinumtoxinA and abobotulinumtoxinA
improve the aesthetic appearance of the skin.21
Similar to the technique used for hyperhidrosis and oily skin,
the effectiveness in reducing symptoms of rosacea along with
preventing adverse muscular dysfunction seems dependent on
injecting the toxin intradermally. We selected a higher dilution
(100 U/7 cc), recognizing that it allows for more spread22 and, in
theory, also reduces the potency of any product that penetrates
past the dermal subcutis junction to reach a specific muscle
group, thereby reducing the possibility of mimetic complication.
The ability to offer a treatment that takes just minutes and
can be performed three to four times per year, obviating the
need for multiple laser treatments, systemic medications, or
daily topical treatments, would provide a desirable alternative
for both the patient and the physician. Rosacea affecting
the face can be a major disruption in one's professional, social,
and family life. Surveys by the National Rosacea Society
indicate that more than 76% of rosacea patients find that the
condition lowers their self-confidence and self-esteem, with
41% reporting that it causes them to avoid public contact
or cancel social engagements.3 The proposed mechanisms
of action responsible for botulinum toxin efficacy in reducing
the symptoms of rosacea are logical, but still not clearly
delineated. Perhaps by inhibiting release of VIP and ACh,
botulinum toxin is inhibiting the effects of two of the known
neurogenic peptides linked to inflammation and vasodilation
in rosacea, or perhaps, the exact mechanisms are yet to
be identified by which botulinum toxin prevents the release
of one of the numerous other neuropeptides involved in sebaceous
activity, vascular homeostasis, and inflammation.
While our results are anecdotal, the curious nature of this
product continues to expand serendipitously to new indications.
A double-blind, randomized, placebo-controlled trial is
in order and expected soon.
Dr. Dayan has been a consultant, investigator, and speaker
for Merz, Medicis, and Allergan.
- Botox® [product insert]. Irvine, CA: Allergan Inc; 2011. http://www.allergan.
com/assets/pdf/botox_pi.pdf. Accessed October 9, 2012.
- Botox® Cosmetic [product insert]. Irvine, CA: Allergan Inc; 2011. http://www.
allergan.com/assets/pdf/botox_cosmetic_pi.pdf. Accessed October 9, 2012.
- Crawford GH, Pelle MT, James WD. Rosacea: I. Etiology, pathogenesis, and
subtype classification. J Am Acad Dermatol. 2004;51(3):327-341.
- Wilkin J, Dahl M, Detmar M, et al. Standard grading system for rosacea: report
of the National Rosacea Society Expert Committee on the classification
and staging of rosacea. J Am Acad Dermatol. 2004;50(6):907-912.
- Olday J, Currie E, Drummond GB. The incidence of flushing on induction of
anaesthesia in patients who blush easily. Anaesthesia. 2003;58(3):275-277.
- Drummond PD, Lance JW. Facial flushing and sweating mediated by the
sympathetic nervous System. Brain. 1987;110(Pt 3):793-803.
- Schwab VD, Sulk M, Seeliger S, et al. Neurovascular and neuroimmune aspects
in the pathophysiology of rosacea.
J Investig Dermatol Symp Proc. 2011;15(1):53-62.
- Holowatz LA, Thompson CS, Minson CT, Kenney WL. Mechanisms of acetylcholine-
mediated vasodilatation in young and aged human skin. J Physiol. 2005;563(Pt 3):965-973.
- Bennett LA, Johnson JM, Stephens DP, Saad AR, Kellogg DL Jr. Evidence for
a role for vasoactive intestinal peptide in active vasodilatation in the cutaneous
vasculature of humans. J Physiol. 2003;552(Pt 1):223-232.
- Yuraitis M, Jacob CI. Botulinum toxin for the treatment of facial flushing. Dermatol Surg. 2004;30(1):102-104.
- Tugnoli V, Marchese Ragona R, Eleopra R, et al. The role of gustatory flushing
in Frey's syndrome and its treatment with botulinum toxin type A. Clin Auton
- Uprus V, Gaylor JB, Carmichael EA. Localized anormal flushing and sweating
on eating. J Nerv Ment Dis. 1937;85(6):724.
- Young AG. Unilateral sweating of the submental region after eating. Br Med
- Drummond PD. Mechanism of gustatory flushing in Frey's syndrome. Clin
Auton Res. 2002;12(3):144-146.
- Sterodimas A, Nicolaou M, Paes TR. Successful use of Botulinum toxin-A for
the treatment of neck and anterior chest wall flushing.
Clin Exp Dermatol. 2003;28(6):592-594.
- Kranendonk SK, Ferris LK, Obagi S. Re: Botulinum toxin for the treatment of
facial flushing. Dermatol Surg. 2005;31(4):491; author reply 492.
- Alexandroff AB, Sinclair SA, Langtry JA. Successful use of botulinum toxin
A for the treatment of neck and anterior chest wall flushing.
Dermatol Surg. 2006;32(12):1536.
- Brin MF, Boodhoo TI, Pogoda JM, et al. Safety and tolerability of onabotulinumtoxinA
in the treatment of facial lines: a meta-analysis of individual patient
data from global clinical registration studies in 1678 participants. J Am
Acad Dermatol. 2009;61(6):961-970. e1-11.
- Zouboulis CC. Acne and sebaceous gland function.
Clin Dermatol. 2004;22(5):360-366.
- Shah AR. Use of intradermal botulinum toxin to reduce sebum production
and facial pore size. J Drugs Dermatol. 2008;7(9):847-850.
- Petchngaovilai C. Midface lifting with botulinum toxin: intradermal technique.
J Cosmet Dermatol. 2009;8(4):312-316.
- Hsu TS, Dover JS, Arndt KA. Effect of volume and concentration on the diffusion
of botulinum exotoxin A. Arch Dermatol. 2004;140(11):1351-1354.