Topical Botulinum Toxin A in the Treatment of Hyperhidrosis

Topically Applied Botulinum Toxin Type A for the Treatment of Primary Axillary Hyperhidrosis: Results of a Randomized, Blinded, Vehicle-Controlled Study

Glogau RG
Dermatol Surg. 2007;33:S76-S80

Primary axillary hyperhidrosis (PAH) is a chronic, idiopathic disorder characterized by supraphysiologic axillary sweating. In many cases, this can lead to significant physical, social, and emotional distress, especially under conditions that stimulate sweat production -- such as heat, stress, and physical exertion.^[1] Treatment options for hyperhidrosis include topical antiperspirants, iontophoresis, oral anticholinergic drugs, surgery (sympathectomy), and botulinum toxin injection.^[2,3] This latter treatment has enjoyed growing popularity, owing to its efficacy, safety, duration of effect, and convenience. As a treatment for severe PAH approved by the US Food and Drug Administration, botulinum toxin A (BTX-A) would be even more popular if it were available in a topically administered form.

Topically applied BTX-A may soon become a clinical reality. In a small pilot study, Glogau reports encouraging initial results with topical BTX-A formulated with a proprietary transport peptide to treat PAH. A similar covalently linked peptide has been used to transport macromolecules, such as insulin, across intact skin, rendering topical administration of BTX-A feasible.

This 4-week, randomized, blinded, internally placebo-controlled study enrolled 12 patients (50% male; mean age, 35 years) with axillary hyperhidrosis defined by a gravimetric measurement of sweat production of at least 50 mg over 5 minutes (while at rest at room temperature). Two subjects were excluded due to asymmetric (> 25% difference) sweat production between axillae, and the remaining 10 subjects completed the trial. Study investigators removed potentially confounding variables, such as anticholinergic medication use, prior BTX-A injection within the past 6 months, and concurrent antiperspirant use. For each subject, topical BTX-A (200 U) vs placebo vehicle creams were randomly applied to contralateral axillae, massaged into the hyperhidrotic areas, and left on the skin for 60 minutes.

The primary outcome measure was reduction in sweat production measured at baseline vs 4 weeks post treatment. Four weeks after treatment, the topical BTX-A formulated in transport peptide cream had reduced the mean gravimetrically measured sweat production by 65%, in contrast to a 25% reduction in the placebo-treated axillae. Local side effects were rare, mild, and as likely to occur in the vehicle-treated as in the BTX-A-treated axillae.

Viewpoint

In this interesting pilot study, Glogau reports encouraging results from a new topically administered form of BTX-A when used to treat primary axillary hyperhidrosis. Regardless of the large size of the BTX-A molecule, investigators have created a proprietary transport peptide system capable of carrying the toxin through intact skin and delivering it to a subcutaneous target (in this case, axillary eccrine glands). The study, although limited by its small size, clearly demonstrated a statistically significant difference in the BTX-A-treated vs vehicle-treated arms, measured 4 weeks after treatment. Investigators could not explain why the placebo-treated axillae also showed a modest reduction in sweat production, although this phenomenon has been observed in another study assessing the efficacy of intradermal BTX-A.^[3]

In sum, topical BTX-A application is presented as an intriguing possibility; however, several key questions remain:

How long does the treatment effect last? Is it comparable to the 6-7 months of sweat reduction commonly reported with intradermal BTX-A injection?^[2,3]
Is topical delivery cost-effective? Given the expense of BTX-A, it seems likely that this answer will be a resounding "no," because 6 months of sweat reduction can be obtained by injecting as little as 50 U BTX-A per axilla (one fourth of the dose used in this study).
Is axillary hyperhidrosis the best place to try topical BTX-A? Intradermal axillary injections are much less painful than palmar and plantar injections. Perhaps future topical BTX-A studies should focus on treating palmar and plantar hyperhidrosis.

Abstract

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