Hyperhidrosis

What is hyperhidrosis?

Hyperhidrosis is the name given to excessive and uncontrollable sweating.

Sweat is a weak salt solution produced by the eccrine sweat glands. These are distributed over the entire body but are most numerous on the palms and soles (with about 700 glands per square centimetre).

Who gets hyperhidrosis?

Primary hyperhidrosis is reported to affect 1–3% of the US population and nearly always starts during childhood or adolescence. The tendency may be inherited, and it is reported to be particularly prevalent in Japanese people.

Secondary hyperhidrosis is less common and can present at any age.

What causes hyperhidrosis?

Primary hyperhidrosis appears to be due to overactivity of the hypothalamic thermoregulatory centre in the brain and is transmitted via the sympathetic nervous system to the eccrine sweat gland.

Triggers to attacks of sweating may include:

• Hot weather
• Exercise
• Fever
• Anxiety
• Spicy food

Causes of secondary localised hyperhidrosis include:

• Stroke
• Spinal nerve damage
• Peripheral nerve damage
• Surgical sympathectomy
• Neuropathy
• A brain tumour
• Chronic anxiety disorder

Causes of secondary generalised hyperhidrosis include:

• Obesity
• Diabetes
• Menopause
• Overactive thyroid
• Cardiovascular disorders
• Respiratory failure
• Other endocrine tumours, eg phaeochromocytoma
• Parkinson disease
• Hodgkin lymphoma
• Drugs: alcohol, caffeine, corticosteroids, cholinesterase inhibitors, tricyclic antidepressants, selective serotonin reuptake inhibitors, nicotinamide and opioids

What are the clinical features of hyperhidrosis?

Hyperhidrosis can be localised or generalised.

• Localised hyperhidrosis affects armpits, palms, soles, face or other sites
• Generalised hyperhidrosis affects most or all of the body

It can be primary or secondary.

Primary hyperhidrosis

• Starts in childhood or adolescence
• May persist lifelong or improve with age
• There may be a family history
• Tends to involve armpits, palms and or soles symmetrically
• Usually, sweating reduces at night and disappears during sleep

Secondary hyperhidrosis

• Less common than primary hyperhidrosis
• More likely to be unilateral and asymmetrical, or generalised
• Can occur at night or during sleep.
• Due to endocrine or neurological conditions

What is the impact of excessive sweating?

Hyperhidrosis is embarrassing and interferes with many daily activities.

Axillary hyperhidrosis

• Clothing becomes damp, stained and must be changed several times a day
• Wet skin folds are prone to chafing, irritant dermatitis and infection

Palmar hyperhidrosis

• Slippery hands lead to avoidance of handshaking
• Marks left on paper and fabrics
• Difficulty in writing neatly
• Malfunction of electronic equipment such as keypads and trackpads
• Prone to a blistering type of hand dermatitis (pompholyx)

Plantar hyperhidrosis

• Affects soles of the feet
• Unpleasant smell
• Ruined footwear
• Prone to a blistering type of dermatitis (pompholyx)
• Prone to secondary infection (tinea pedis, pitted keratolysis)

How is hyperhidrosis diagnosed?

Hyperhidrosis is usually diagnosed clinically. Tests relate to the potential underlying cause of hyperhidrosis and are rarely necessary for primary hyperhidrosis.

The precise site of localised hyperhidrosis can be revealed using the Minor test.

• Iodine (orange) is painted onto the skin and air dried.
• Starch (white) is dusted on the iodine.
• Sweating is revealed by a change to dark blue/black colour.

Screening tests in secondary generalised hyperhidrosis depend on other clinical features but should include as a minimum:

• Blood sugar / glycosylated haemoglobin
• Thyroid function

What is the treatment of hyperhidrosis?

General measures

• Wear loose-fitting, stain-resistant, sweat-proof garments.
• Change clothing and footwear when damp.
• Socks containing silver or copper reduce infection and odour.
• Use absorbent insoles in shoes and replace them frequently.
• Use a non-soap cleanser.
• Apply corn starch powder after bathing.
• Avoid caffeinated food and drink.
• Discontinue any drug that may be causing hyperhidrosis.
• Apply antiperspirant.

Topical antiperspirants

• Deodorants are fragrances or antiseptics to disguise unpleasant smells; on their own, they do not reduce perspiration.
• Antiperspirants contain 10–25% aluminium salts to reduce sweating; "clinical strength" aluminium zirconium salts are more effective than aluminium chloride. 
• Topical anticholinergics such as glycopyrrolate and oxybutynin gel have been successful in reducing sweating; cloths containing glycopyrronium tosylate (Qbrexza™) were approved by the FDA in July 2018 for axillary hyperhidrosis in adults and children 9 years of age and older. Dusting powder is available containing the anticholinergic drug, diphemanil 2%.
• Antiperspirants are available as a cream, aerosol spray, stick, roll-on, wipe, powder, and paint.
• Specific products are available for different body sites such as underarms, other skin folds, face, hands and feet.
• They are best applied when skin is dry, after a cool shower just before sleep.
• Wash off in the morning if tending to irritate.
• Use from once weekly to daily if necessary.
• If irritating, apply hydrocortisone cream short-term.

Iontophoresis

• Iontophoresis is used for hyperhidrosis of palms, soles and armpits.
• Mains and battery-powered units are available.
• The affected area is immersed in water, or, with a more significant effect, glycopyrronium solution.
• A gentle electrical current is passed across the skin surface for 10–20 minutes.
• Repeated daily for several weeks then less frequently as required
• Iontophoresis may cause discomfort, irritation or irritant contact dermatitis.
• The treatment requires a long-term commitment.
• It is not always effective.

Oral medications

Oral anticholinergic drugs

• Available drugs are propantheline 15–30 mg up to three times daily, oxybutynin 2.5–7.5 mg daily, benztropine, glycopyrrolate (unapproved).
• They can cause dry mouth, and less often, blurred vision, constipation, dizziness, palpitations and other side effects.
• People with glaucoma or urinary retention should not take them.
• Caution in elderly patients: increased risk of side effects is reported, including dementia.
• Oral anticholinergics may interact with other medications.

Beta-blockers

• Beta blockers block the physical effects of anxiety.
• They may aggravate asthma or symptoms of peripheral vascular disease.

Calcium channel blockers, alpha adrenergic agonists (clonidine) nonsteroidal anti-inflammatory drugs and anxiolytics may also be useful for some patients.

Botulinum toxin injections

• Botulinum toxin injections are approved for hyperhidrosis affecting the armpits.
• The injections reduce or stop sweating for three to six months.
• Botulinum toxins are used off-license for localised hyperhidrosis in other sites such as palms.
• Topical botulinum toxin gel is under investigation for hyperhidrosis.

Surgical removal of axillary sweat glands

Overactive sweat glands in the armpits may be removed by several methods, usually under local anaesthetic.

• Tumescent liposuction (sucking them out)
• Subcutaneous curettage (scraping them out)
• Microwave thermolysis (the MiraDry® system approved by FDA in 2011)
• Subdermal Nd:YAG laser
• High-intensity micro-focused ultrasound (experimental)
• Surgery to cut out the sweat gland-bearing skin of the armpits. If a large area needs to be removed, it may be repaired using a skin graft

Sympathectomy

Division of the sympathetic spinal nerves by chemical or surgical endoscopic thoracic sympathectomy (ETS) may reduce sweating of face (T2 ganglion) or armpit and hand (T3 or T4 ganglion) but is reserved for the most severely affected individuals due to potential risks and complications.

• Hyperhidrosis may recur in up to 15% of cases.
• Sympathectomy is often accompanied by undesirable skin warmth and dryness.
• New-onset hyperhidrosis of other sites occurs in 50–90% of patients, and is severe in 2%. It is reported to be less frequent after T4 ganglion sympathectomy compared with T2 ganglion sympathectomy.
• Serious complications include Horner syndrome, pneumothorax (in up to 10%), pneumonia and persistent pain (in fewer than 2%).

Lumbar sympathectomy is not recommended for hyperhidrosis affecting the feet, as it can interfere with sexual function.

What is the outlook for hyperhidrosis?

Localised primary hyperhidrosis tends to improve with age. The outlook for secondary localised or generalised hyperhidrosis depends on the cause.

Future treatments for hyperhidrosis

Several research projects are underway to find safer and more effective treatments for hyperhidrosis. These include:

• Topical anticholinergic DRM04
• Combination of oxybutynin and pilocarpine (to counteract the adverse effects of the anticholinergic, oxybutynin) THVD-102