The Treatment of Primary Focal Hyperhidrosis

Todd Wechter, BSc; Steven R. Feldman, MD, PhD; Sarah L. Taylor, MD, MPH

Disclosures

Skin Therapy Letter. 2019;24(1) 

In This Article

Local Non-surgical Therapies

Topical Therapies

Topical antiperspirants are generally regarded as first-line options for primary focal hyperhidrosis and can be used as initial therapy for palmoplantar, axillary or craniofacial disease.[3,4,8] They are considered effective with a reasonable side effect and cost profile.[9] Typically, aluminum chloride based antiperspirants are used, which precipitate with mucopolysaccharides, damage ductal epithelial cells and block the duct, ultimately preventing sweat secretion (Figure 1E).[3,10] In mild cases, over-the-counter aluminum chloride based medications may prove effective, although for more severe cases, prescription aluminum chloride hexahydrate at concentrations of 10% to 35% is recommended.[3,4,8,11] Aluminum chloride based antiperspirants require continued administration, as the injured epithelium of the eccrine duct will eventually redevelop; although prolonged administration can result in persistent damage to eccrine glands and produce a more durable response.[3,4,10]

One study of 20 patients with plantar hyperhidrosis demonstrated that aluminum chloride hexahydrate at concentrations of both 12.5% and 30% produced an approximately 52% decrease in sweating after 6 weeks of treatment, as assessed by Minor's iodine sweat test.[12] Another study of 20% aluminum sesquichlorohydrate foam for palmar and axillary disease demonstrated a mean 61% reduction in Minor score after 4 weeks of treatment.[13]

Local skin irritation is the major side effect of topical aluminum based antiperspirant therapy, although non-alcohol containing formulations, such as aluminum chloride hexahydrate in salicylic gel, may be more tolerable.[14] Application of white petroleum jelly prior to aluminum chloride antiperspirant application can also help to prevent skin irritation.[15]

Topical anticholinergic therapy is another emerging treatment option for hyperhidrosis that likely works through hindering cholinergic activation of eccrine glands (Figure 1C).[3,16] In a prospective study of 40 patients with axillary hyperhidrosis, treatment with 2% glycopyrrolate spray decreased sweating similar to botulinum toxin type A injections.[17] Another randomized, double-blind, split area study of patients with palmar, plantar or axillary disease found that 10% topical oxybutynin treatment resulted in a mean Dermatology Life Quality Index (DLQI) score reduction of 7.6 points when compared to pretreatment scores.[18] Topical anticholinergic therapies such as umeclidinium and glycopyrronium are also being further studied in clinical trials.[16,19,20] In particular, glycopyrronium tosylate topical wipes (DRM04, Qbrexza™), recently approved by the US FDA, have been shown to be well tolerated and efficacious for the treatment of axillary disease.[20] In two recent phase 3 clinical trials, patients treated with once daily DRM04 topical wipes experienced significant improvement in Axillary Sweating Daily Diary scores (ASDD) and in sweat production as measured by gravimetry.[20]

Iontophoresis

Iontophoresis involves passing an electrical current through the skin and is an acceptable first-line treatment for palmoplantar hyperhidrosis after a trial of topical antiperspirants for more severe disease.[8,21] Patients submerge their hands and/or feet in tap water and an electrical current is applied.[21] Although its exact mechanism of action remains unknown, therapy does not alter the structure of the glands.[22] Iontophoresis is effective with the added benefit of at-home treatment options.[23]

In a recent clinical trial examining patients treated with tap water iontophoresis for palmar disease, approximately 93% of patients had symptomatic improvement after 2 weeks of treatment, as measured by starch-iodine test, compared to 38.5% in the sham group.[24] Gravimetric analysis revealed that iontophoresis treated patients had a mean reduction in sweat rate of 91.8% and 69% at 2 and 6 weeks post-treatment, respectively.[24] Another study demonstrated that with tap water iontophoresis treatment 3 days per week for 4 weeks, patients experienced on average a 75% and 65% reduction of symptoms on their palms and soles, respectively, as measured by self-assessed disease severity scores.[25]

Iontophoresis can also be used as a mechanism to deliver other medications such as aluminum chloride and anticholinergics.[26–28] For example, in a 2011 study of 22 patients with palmar hyperhidrosis, treatment with glycopyrronium bromide iontophoresis resulted in a 54% reduction of mean sweat production as measured by gravimetry.[28]

Side effects of iontophoresis are generally mild and their severity may depend on the voltage and current used, and can include local skin irritation, pain and burns.[25,29]

Botulinum Toxin

Botulinum toxin type A (BTX-A) is generally considered a second-line therapy for primary focal hyperhidrosis, although in severe or craniofacial disease it can be considered for first-line use.[8] The treatment is effective, however, it is invasive and more expensive than topical options and typically requires repeated administration.[30] The injected toxin acts by cleaving the SNARE protein complex, which is required for the pre-synaptic release of acetylcholine, thus halting its effect on the eccrine gland (Figure 1B).[31]

One randomized, double-blind, multi-institution, prospective study of 207 patients with axillary disease found that 4 weeks after their first BTX-A injection patients experienced a mean decrease in sweat production of 84.6% as measured by gravimetry.[32] Furthermore, approximately 96% of patients reported higher satisfaction with BTX-A injection compared to previous treatments they had received.[32] Another 2008 study demonstrated that axillary injection with BTX-A is more effective when compared to topical 20% aluminum chloridebased antiperspirants in patients with moderate to severe disease (mean Hyperhidrosis Disease Severity Scale [HDSS] reduction of 2.4 vs.1.33 at 4 weeks of therapy, respectively, p<0.0001).[33] Long-term use of BTX-A is safe and effective, and repeated injections may increase the duration of symptomatic relief.[34] In a retrospective study of patients receiving a mean of 4 axillary BTX-A injection sessions, the last injection resulted in a 3 month longer median duration of efficacy compared to the first injection.[34]

Side effects are typically minor and include pain and irritation at the injection site, subjective feeling of increased sweating and reversible muscle weakness.[32–35] Pain from the injection is sometimes a limitation of the therapy, although studies of less painful administration methods such as diluting BTX-A in lidocaine or transdermal jet nebulization have been promising.[36,37]

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