Hyperhidrosis

Management Strategy

The treatments discussed here apply to primary idiopathic hyperhidrosis. Therapy for secondary hyperhidrosis should be directed toward the underlying condition. Simple conservative measures can be advocated as an adjunct to treatment:

• Acknowledging what a difficult condition this can be is often validating

• Inform the patient about support groups such as Hyperhidrosisuk.org or SweatHelp.org

• Provide advice regarding practical measures such as:

  • wear absorbent underlayers such as loose-fitting cotton T-shirts

  • use adhesive underarm pads or absorbent insoles

  • wear cotton socks with leather shoes and, if necessary, change socks and shoes throughout the day

The evidence on all of the following treatments is of limited quality and predominantly comprises small, non-randomized, retrospective, observational studies and case series with a high risk of bias. Nevertheless, many patients respond well to available treatments and current recommendations are based on expert consensus. Plantar hyperhidrosis, as well as inframammary, groin, and buttock hyperhidrosis, may be complicated by secondary bacterial and fungal overgrowth and may require additional topical treatment.

Topical aluminum chlorohydrate (Al ₂ Cl(OH) ₆ ) antiperspirants are the first-line treatment. Aluminum-based complexes react with the electrolytes in sweat to form a gel plug causing a functional inability of the gland to produce sweat. Correct application technique is crucial: in the axillae, the solution should be applied at night to unshaven skin and washed off the next morning before daytime sweating is established. The skin must be dry during application as the presence of moisture results in hydrochloric acid formation and skin irritation. To prevent this, the skin should be gently dabbed dry or blow-dried. Mild-potency topical corticosteroids may be used to reduce the common problem of skin irritation, which is the usual reason for treatment failure. Application of yellow soft paraffin to axillary margins can also minimize irritation. Hyperhidrosis may take 2–3 weeks to be controlled with aluminum chlorohydrate, at which time application can be reduced to once or twice a week, or any interval that maintains control. Formulas with concentrations of 15%–20% are commercially available and used for most areas of the body, although concentrations of 20%–40% are typically used for the soles of the feet.

Iontophoresis is a process of transdermal delivery of an ionized substance (typically sodium) through intact skin using a voltage gradient. It is predominantly reserved for palmoplantar hyperhidrosis. Several iontophoretic devices are commercially available and patients typically need to purchase them. Plug-in variants are superior to battery-operated ones. It is cost-effective in the long term. Cheap homemade variants are increasingly becoming popular, but their efficacy is not validated.

The precise mechanism through which sweating is reduced is unknown given that the current densities employed are below the threshold known to cause damage to the acrosyringium, as well as the fact that mechanical obstruction does not occur. Iontophoresis is contraindicated in patients with cardiac pacemakers or defibrillators and metal implants, as well as in pregnancy.

A direct current is transmitted to electrodes in two trays filled with hard tap water (or soft water with an added teaspoon of sodium bicarbonate/baking soda per tray), and the hands or feet are placed flat in the bottom of the trays. The current is increased until the patient experiences slight discomfort (typically 15 mA for the palms and 20 mA for the soles). Three sessions a week of 20–30 min each are continued for approximately 6 weeks until sweating is sufficiently reduced; thereafter, the frequency can be dropped to once weekly as maintenance. Treatments need to be conducted regularly and before sweating begins to return in order to maintain dryness.

The anticholinergic drug glycopyrrolate can be added (2 mg per tray) to increase efficacy. Alternatively, 2% glycopyrrolate cream can be applied the night before tap water iontophoresis. Unfortunately, glycopyrrolate can be expensive as it may need to be imported. A special electrode for axillary use is available for some iontophoretic devices, but appears to be less effective due to poor contact.

Botulinum toxin injected intradermally produces sustained anhidrosis by irreversibly blocking the release of acetylcholine from cholinergic junctions. New cholinergic junctions are produced through the natural process of tissue turnover and repair, so the effect is temporary. Anhidrosis occurs within 24 to 72 hours and lasts on average 6 months.

It has shown high efficacy in the treatment of axillary, palmar, craniofacial, postamputation stump hyperhidrosis, compensatory sweating, and Frey syndrome. The commercially available botulinum toxin A products (Botox, Dysport, Xeomin, and Jeuveau) differ in their potency and are not equivalent unit for unit.

Botulinum toxin injected into the axilla is simple and well tolerated with a 90% reduction in sweating expected. Multiple injections, 1–2 cm apart in a grid pattern, are performed in the axillary vault corresponding to the area of maximum sweating (an area of approximately 200 cm ² ). Typically, 50 units of Botox are injected into each axilla, but larger males ideally should be treated with 100 units per axilla. Several reports describe the increase in duration of efficacy of repeated treatments over time.

Palmar skin is responsive to botulinum toxin with good outcomes, but use is precluded by the need for regional anesthesia due to pain. Local anesthetic nerve blocks, cryoanesthesia, or nitrous oxide (Entonox) inhalation have been employed. The latter is a safe and simple method that provides adequate anesthesia for the duration required. Twice the number of injections as the axilla is required. Avoiding injection into the thenar eminence minimizes the risk of weakening small muscles of the hand. Administration of botulinum toxin to the palms by iontophoresis or by needle-free injectors is still largely experimental.

Botulinum toxin injections work well for craniofacial hyperhidrosis, injecting along the hairline. It is rarely used for plantar hyperhidrosis as it less effective and more painful at this site.

Oral anticholinergic drugs produce a dose-related inhibition of sweating and are best suited for patients with generalized hyperhidrosis and craniofacial hyperhidrosis, and those with focal forms of hyperhidrosis that do not respond to more localized approaches. The main limitations of treatment are anticholinergic side effects. Medications in this class include glycopyrrolate, oxybutynin, benztropine, and propantheline. In the UK, only propantheline is licensed for this indication; the other agents are used off-label.

Side effects include dry mouth and impaired taste, pupillary dilatation and blurred vision, glaucoma, urinary retention, constipation, and tachycardia. Overheating can occur due to too effective a block on sweating. There is some evidence that they may increase the risk of dementia in the elderly. Typical prescribed doses include glycopyrrolate 2 mg three times daily; slow release oxybutynin, starting at 5 mg daily, increasing to a maximum of 20 mg daily; and propantheline 15 mg three times daily (this should be taken on an empty stomach and has a half-life of 6 hours). Glycopyrrolate and oxybutynin have liquid formulations that can be prescribed to children and are also significantly cheaper.

Topical glycopyrrolate tosylate (Qbrexza) has been approved by the US Food and Drug Administration (FDA) in 2018 and comes in individually packaged cloths (or wipes) that are to be used at home once per day – with one wipe used for two axillae.

Other systemic drugs that have been used in hyperhidrosis include β-blockers and benzodiazepines, which inhibit the physical manifestations of anxiety and are best suited for patients with episodic or event-driven hyperhidrosis such as during oral presentations, examinations, or job interviews. Agents such as clonidine, indomethacin, gabapentin, and diltiazem all have a few anecdotal reports of their use. Clonidine at a dose of 0.1 mg twice daily is recommended for women beyond the menopause who suffer from troubling hyperhidrosis if anticholinergic agents are ineffective; however, drowsiness is the main limiting side effect.

Surgical and physical techniques are generally used as third-line options.

Microwave-based devices such as miraDry, approved by the FDA in 2011, are believed to work by causing thermolytic injury to localized sweat glands. Neodymium:yttrium-aluminum-garnet (nd:YAG) laser used with an interstitial fiber; photodynamic therapy using an eosin photosensitizer; and fractional microneedle radiofrequency devices may also work by causing tissue destruction using electromagnetic energy.

Sympathectomy involves the selective ablation of the sympathetic innervation and reduces sweating effectively and with satisfactory long-term results, improved quality of life, and low recurrence rates. It is performed endoscopically through a transthoracic route using electrocautery or laser. It has been shown to be successful in children and adolescents. Unfortunately, it may result in a number of severe complications including compensatory hyperhidrosis (which for many patients is even more debilitating), Horner syndrome, pneumothorax, and intraoperative cardiac arrest. It is best reserved for severe palmar hyperhidrosis with an upper thoracic sympathectomy performed at the T2–T3 ganglion. Lumbar sympathectomy for plantar hyperhidrosis is not recommended due to the significant risks of ejaculatory failure, impotence, and anorgasmia.

Underarm surgery techniques include excision, subcutaneous curettage, and liposuction – all performed under local anesthesia. Combinations of these approaches can be employed, and the results are typically permanent due to the destruction of sweat glands. Several skin incisions and reconstructive flaps are described to gain access to the subcutaneous axillary tissues in order to trim away the deep dermis and subcutaneous tissue. The Shelley procedure is a minimally invasive procedure that involves the removal of dermal eccrine sweat glands and denervation of other sweat glands through a central axillary incision with reinnervation being disrupted by subsequent scar formation. This method is noted to have a higher rate of postoperative infection with both systemic and topical antimicrobial prophylaxis recommended.

Tests are not necessary for a diagnosis of most cases of focal hyperhidrosis; however, investigation appropriate to the clinical history and physical examination is necessary when hyperhidrosis is generalized.