Medical Care
Therapy for hyperhidrosis can be challenging for both the patient and the physician. Both topical and systemic medications have been used in the treatment of hyperhidrosis. Other treatment options for hyperhidrosis include iontophoresis and botulinum toxin injections.
Topical agents for hyperhidrosis therapy include topical anticholinergics, boric acid, 2-5% tannic acid solutions, resorcinol, potassium permanganate, formaldehyde (which may cause sensitization [27] ), glutaraldehyde, and methenamine. All of these agents are limited by staining, contact sensitization, irritancy, or limited effectiveness. These agents reduce perspiration by denaturing keratin and thereby occluding the pores of the sweat glands. They have a short-lasting effect.
The US Food and Drug Administration (FDA) approved glycopyrronium tosylate topical cloth in June 2018 for primary axillary hyperhidrosis in adults and children aged 9 years or older. It is an anticholinergic agent that inhibits the action of acetylcholine on sweat glands. Approval was based on results from two phase 3 clinical trials, ATMOS-1 and ATMOS-2 (n=697). Of these, 44 were pediatric patients aged 9-16 years. The proportions of patients experiencing a reduction of at least 50% in sweat production at 4 weeks for pediatric versus adult patients were 79.9% versus 74.3% of glycopyrronium tosylate–treated patients compared with 54.8% versus 53% of vehicle-treated patients, respectively. [28, 29] Topical glycopyrronium tosylate has been judged as a cost-effective measure relative to prescription aluminum chloride. [30]
Contact sensitization is increased, especially with formalin. Aldehydes are used to treat the palms and soles; they are not as effective in the axillae. Glutaraldehyde solution 2% is sold as Cidex. It is not as effective but less staining. The 20-50% solution can be diluted to 10% (more effective, especially for feet, but still staining occurs).
Because of the limitations of other agents, Drysol (20% aluminum chloride hexahydrate in absolute anhydrous ethyl alcohol) is more commonly used as the first-line topical agent. Drysol should be applied nightly on dry skin with or without occlusion until a positive result is obtained, after which the intervals between applications may be lengthened. To minimize irritation, the remainder of the medication should be washed off when the patient awakes, and the area may be neutralized with the topical application of baking soda. [31]
Axillary hyperhidrosis may be treated with aluminium chloride gel, although the gel may cause mild cutaneous irritation. [32] Its antiperspirant action for treatment of palmar hyperhidrosis and its low risk of systemic adverse effects from absorption and accumulation of aluminium in visceral organs are noteworthy. [33] Use of a novel microwave device has been suggested for axillary hyperhidrosis. [34] A single high-energy microwave treatment may be efficacious for selected patients with primary axillary hyperhidrosis. [35]
Systemic agents used to treat hyperhidrosis include anticholinergic medications. Anticholinergics such as propantheline bromide, glycopyrrolate, oxybutynin, [36] and benztropine are effective because the preglandular neurotransmitter for sweat secretion is acetylcholine (although the sympathetic nervous system innervates the eccrine sweat glands). [37, 38] The use of anticholinergics may be unappealing because their adverse effect profile includes mydriasis, blurry vision, dry mouth and eyes, difficulty with micturition, and constipation. In addition, other systemic medications, such as sedatives and tranquilizers, indomethacin, and calcium channel blockers, may be beneficial in the treatment of palmoplantar hyperhidrosis.
Iontophoresis was introduced in 1952 and consists of passing a direct current across the skin. [39, 40, 41] The mechanism of action remains under debate. In palmoplantar hyperhidrosis, the daily treatment of each palm or sole for 30 minutes at 15-20 mA with tap water iontophoresis is effective. [42] Intact skin can endure 0.2-mA/cm2 galvanic current without negative consequences, and as much as 20-25 mA per palm may be tolerated. [42] Numerous agents have been used to induce hypohidrosis, including tap water and anticholinergics; however, treatment with anticholinergic iontophoresis is more effective than tap water iontophoresis. [43] However, the latter is safe and effective when used on Monday, Wednesday, and Friday for 4 weeks, with continued treatment maintaining the effect. [44] Noncompliance is common with tap water iontophoresis, as it can be time-consuming. [45] This technique merits consideration prior to systemicoraggressive surgical intervention.
Botulinum toxin injections are effective because of their anticholinergic effects at the neuromuscular junction and in the postganglionic sympathetic cholinergic nerves in the sweat glands. [46, 47, 48, 49, 50]
In palmar hyperhidrosis, 50 subepidermal injections of 2 mouse units per palm (total 100 mouse units per palm) results in anhydrosis lasting 4-12 months. [51] Each injection produces an area of anhydrosis approximately 1.2 cm in diameter. The only adverse effect is mild transient thumb weakness that resolves within 3 weeks. Adverse effects of intradermal injections of botulinum A toxin may result from diffusion into underlying muscles. [52] A substantial increase in the duration of efficacy may be produced by repetitive injections in those with primary palmar hyperhidrosis. [53]
In a similar study, the effects of sodium chloride solution injections in one palm were compared with botulinum toxin injections in the other palm. [54] Treatment with 120 mouse units of botulinum toxin (injected into 6 sites in the palm) resulted in a 26% reduction in sweat production after 3 and 8 weeks and a 31% reduction after 13 weeks. Noted adverse effects included minor muscle weakness at the toxin-treated sites, which resolved after 2-5 weeks. Injections of botulinum toxin must be repeated at varying intervals to maintain long-term results.
Treatment of axillary hyperhidrosis with botulinum toxin type A reconstituted in lidocaine or in normal saline was described in a randomized, side-by-side, double-blind study. [55] The results were the same; however, injections of botulinum toxin A reconstituted in lidocaine are associated with significantly reduced pain, thus, lidocaine-reconstituted botulinum toxin A may be preferable for treating axillary hyperhidrosis.
A 2008 study found botulinum toxin type A to be more effective than topical 20% aluminum chloride for the treatment of moderate-to-severe primary focal axillary hyperhidrosis. [56]
Woolery-Lloyd et al reported on successful treatment of inguinal hyperhidrosis with botulinum toxin A. The condition was initially misdiagnosis as urinary incontinence. [57]
Bromhidrosis may be treated with a glycine-soja sterocomplex topical agent, which has shown encouraging results on both the intensity and quality of odor in patients with bromhidrosis. [58]
Surgical Care
In addition to pharmacologic therapy, other treatments include surgical sympathectomy, radiofrequency ablation, [59] surgical excision of the affected areas, and subcutaneous liposuction. Each modality has been used effectively. Use of microneedle radiofrequency therapy for axillary hyperhidrosis has been recommended. [60]
Palmar hyperhidrosis is a benign functional disorder that is a psychological and social handicap. [61] A survey showed thoracoscopic sympathectomy to be minimally invasive and to improve the patient's quality of life, even if compensatory hyperhidrosis occurs.
Sympathectomy has been used as a permanent effective treatment since 1920. Usually, it is reserved for the final treatment option. [62] Sympathectomy involves the surgical destruction of the ganglia responsible for hyperhidrosis. [63, 64, 65] Sympathectomy for hyperhidrosis treatment requires an inpatient stay. Modified R5-R8 thoracic sympathectomy has been used for severe compensatory hyperhidrosis. [66]
The second (T2) and third (T3) thoracic ganglia are responsible for palmar hyperhidrosis, the fourth (T4) thoracic ganglia controls axillary hyperhidrosis, and the first (T1) thoracic ganglia controls facial hyperhidrosis.
Two surgical approaches are available: an open approach and a newer endoscopic approach. The endoscopic approach has become favored because of its improvements in terms of complications, surgical scars, and surgical times. Endoscopic thoracic sympathectomy is an effective treatment for hyperhidrosis; in one study, immediate positive results occurred in 832 (98%) of 850 patients. [20] After a 31-month average follow-up, symptoms recurred in 17 patients. Improved quality of life has been described for upper limb hyperhidrosis after treatment with limited endoscopic thoracic sympathetic block at T4. [67]
Numerous complications are associated with this endoscopic treatment option; these include compensatory sweating (induction of sweating in previously unaffected areas of the body), gustatory sweating, pneumothorax, intercostal neuralgia, Horner syndrome, recurrence of hyperhidrosis, and the sequelae of general anesthetic use.
Of 850 patients who underwent endoscopic transthoracic sympathectomy, 55% had compensatory sweating (mostly on the trunk), and 36% had gustatory sweating. [20] In a similar study [68] of 72 patients who underwent transthoracic endoscopic sympathectomy (T2 or T2 and T3) for palmar hyperhidrosis, the success rate was 93%; compensatory sweating occurred in an overwhelming 99% of patients within 1 month after surgery, and gustatory sweating occurred in 17%. The overall occurrence of severe compensatory hyperhidrosis was reduced after T3 ganglionectomy as opposed to ganglionectomies performed at all other levels. [69] .
T4 ganglion interruption for palmar hyperhidrosis is an effective approach that can simultaneously minimize the rate of compensatory hyperhidrosis. [70] Thus, T4 sympathectomy may be an effective cure. Its rate of compensatory hyperhidrosis appears to be remarkably low compared with T2 sympathetic ganglionic interruption. An effective treatment for such compensatory sweating is the intradermal injection of botulinum toxin. [71]
Li et al reported on minimizing endoscopic thoracic sympathectomy for hyperhidrosis of the palms using the skin temperature of the palms and Doppler-guided blood flow analysis as aids. [72]
Video-assisted thoracic sympathectomy may be preferable to no treatment for children with palmar hyperhidrosis and a poor quality of life. [73]
Topical glycopyrrolate application may be effective and safe for the treatment of excessive facial sweating in primary craniofacial and secondary gustatory hyperhidrosis following sympathectomy. [74]
Surgical excision of the affected area (identified with iodine starch testing) removes the appropriate sweat glands, thereby eliminating sweating. This technique is particularly useful in axillary hyperhidrosis.
The treatment of axillary hyperhidrosis using the 1064-nm Nd-YAG laser was found to be effective and safe in a pilot trial. [75] Fractional carbon dioxide laser–assisted botulinum toxin type A (onabotulinumtoxinA) delivery for the treatment of primary palmar hyperhidrosis has also been used. [76] Radiofrequency thermotherapy has also been recommended. [77]
Subcutaneous liposuction is another means of removing the eccrine sweat glands responsible for axillary hyperhidrosis. Compared with classic surgical excision, this modality results in less disruption to the overlying skin, resulting in smaller surgical scars and a diminished area of hair loss. [78]
Consultations
Consult a neurosurgeon if sympathectomy is necessary in severe cases of hyperhidrosis that are refractory to all other treatments.
Long-Term Monitoring
Many of the treatment options for hyperhidrosis require repeat visits to the dermatologist for continuing care (eg, repeated botulinum injections, refill prescriptions) and for evaluating therapeutic progress.
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Hyperhidrosis of the palms. Courtesy of DermNet New Zealand (http://www.dermnetnz.org/assets/Uploads/hair-nails-sweat/hyperhidrosis.jpg).
