Mechanism of action

Aluminum salt solutions are the most common antiperspirants in use today.[58] Aluminum chloride is the partially neutralized form used in cosmetic antiperspirants, while aluminum chloride hexahydrate is among the most effective antiperspirants currently available.[58] Several studies have shown that aluminum salts cause an obstruction of the distal sweat gland ducts.[59] A mechanism underlying this obstruction has been proposed: the metal ions precipitate with mucopolysaccharides, damaging epithelial cells along the lumen of the duct and forming a plug that blocks sweat output.[58] Sweat is still produced, as evidenced by the appearance of miliaria (prickly heat) during heat stress, with sweat building up behind the obstruction created by the metallic salt.[59] Normal sweat gland function returns with epidermal renewal, however, necessitating retreatment once or twice a week.[58]

Long-term histologic studies of eccrine glands in patients on chronic aluminum salt treatment have shown destruction of secretory cells, accounting for the clinical finding of reduced severity of hyperhidrosis, as reflected by the need for less-frequent treatments.[59] Other metallic salts such as zirconium, vanadium, and indium are thought to work by the same mechanism.[58] Some of these salts are more effective than aluminum salts, but aluminum salts have been used for over 80 years, are inexpensive and nontoxic, and remain the common active ingredient of most preparations.[58]

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Treating axillary sweating

Aluminum chloride therapy, mostly effective for axillary hyperhidrosis, was first described in 1916.[23] Scholes and colleagues treated 65 patients with 20% aluminum chloride hexahydrate in absolute alcohol and found that 64 of the patients reported excellent control of axillary sweating.[126] A double-blind placebo trial of 20% aluminum chloride hexahydrate in patients waiting for surgery showed 24 of 38 to be improved, of which 19 decided against surgery.[109]

In a study involving 691 patients with axillary hyperhidrosis treated with aluminum chloride, 82% of the group reported dryness or a tolerable amount of sweating, and, over longer follow-up, 87% reported satisfaction with the treatment.[58] In that study, various concentrations were evaluated, and the authors concluded that 15% was as effective as 20% and was better tolerated.

Treating palmar sweating

 
Palmar hyperhidrosis is less responsive to aluminum chloride therapy,[148] and successful treatment may require concentrations up to 30%.[145] An evaporimeter was used in 12 patients with palmar hyperhidrosis to measure skin water vapor loss after treatment with 20% aluminum chloride; the water loss was reduced by 17% at one week and by 30% at four weeks, compared to the untreated palms. The effect was noted 48 hours after starting treatment, and sweating increased again 48 hours after stopping treatment.[44]

Side effects

 
There are individual case reports and small series of patients with facial hyperhidrosis or gustatory sweating (Frey’s syndrome) who had a clinical response to aluminum chloride treatment.[17,119,146] The most common adverse effects of aluminum chloride treatment are itching and stinging immediately after application and ongoing skin irritation.[58] In one series of 691 patients, pruritus was slight and short in duration in 70%, moderate in 21%, and severe in 9%, while skin irritation was moderate in 36% and severe in 14%. During maintenance treatment, less itching and skin irritation were seen.[58] Damage to fabrics also occurs, so expensive nightwear should be avoided.[145]

Available forms

 
Available by prescription, 20% aluminum hexahydrate in anhydrous ethanol (Drysol, Person and Covey, Inc., Glendale, California) is a commonly used agent.[134] Concentrations of 10% to 15% and up to 30% are used in compounded formulations to treat axillary and palmoplantar hyperhidrosis, respectively.[145]

Recommended regimen

 
Following a recommended regimen may enhance efficacy and reduce the incidence of adverse effects.[148] Aluminum chloride should remain on the skin for 6 to 8 hours to be effective. Overnight application is done to take advantage of low sweat output during sleep; diffusion of the aluminum ions into the sweat gland may be impossible if the gland is actively excreting sweat.[58] If the patient regularly shaves the axillary region, it is best to wait 24 to 48 hours after shaving before applying the medication to decrease irritation.[148] Irritating hydrochloric acid forms in the presence of water, so prewashing is not advised; drying the axillae with a blow dryer may reduce irritation. [148] In the morning, the medication should be washed off before daytime sweating begins.[148] Irritated skin can be treated with topical HC cream for up to two weeks if irritation persists.[134] If irritation persists beyond that point, a dermatology consult should be obtained. Nightly treatments are recommended until an effect is noted, and then the interval between treatments can be lengthened.[134]

Using occlusion and alternative vehicles

 
Other approaches to aluminum chloride therapy include the addition of occlusion, with plastic wrap in the axillae and on the feet and vinyl gloves on the hands. This is recommended if the above regimen is not effective.[148] However, another study showed that plastic film occlusion over the aluminum-salt-treated area was not necessary.[23]

Changing the vehicle could also enhance efficacy or reduce irritation. Although many recommend absolute alcohol as the best vehicle for minimizing irritation, a large series of patients followed for as long as a decade has shown that an aqueous vehicle thickened with methylcellulose to create a gel was the most effective formulation.[58] In a double-blind trial in 30 patients with axillary hyperhidrosis, triethanolamine was applied after aluminum chloride treatment to neutralize the irritating hydrochloric acid formed.[41] Although there was a statistically significant reduction in skin irritation, sweat reduction dropped from 75% with aluminum chloride alone to 55% with the combination treatment.

In a more recent study, 4% salicylic acid in a hydroalcoholic gel base was used as the vehicle for aluminum chloride hexahydrate in 238 patients with hyperhidrosis involving the axillae, feet, hands, and groin.[14] The reasons for using this combination included possible enhancement of aluminum chloride absorption by salicylic acid, possible additional antiperspirant effects of salicylic acid, and potentially less skin irritation afforded by the hydroalcoholic gel. The percentage of aluminum chloride varied with the site treated—10% to 25% for the axillae and 30% to 40% for the palms and soles. For patients with axillary disease, 94% reported excellent-to-good results. Excellent-to-good results were reported by 60% and 84% of patients with palmar or plantar involvement, respectively. Patients who had previously failed to respond to aluminum chloride in absolute alcohol or could not tolerate it seemed to improve with use of the salicylic acid gel vehicle. The researchers were unable to do a double-blind comparison, as the two topical applications had different consistencies. The researchers also suggest further study using more-objective outcome measures.