(See also Introduction to Sweating Disorders.)
Etiology
Hyperhidrosis can be focal or generalized.
Focal sweating
Emotional causes are common, causing sweating on the palms, soles, axillae, and forehead at times of anxiety, excitement, anger, or fear. It may be due to a generalized stress-increased sympathetic outflow. Sweating is also common during exercise and in hot environments. Although such sweating is a normal response, patients with hyperhidrosis sweat excessively and under conditions that do not cause sweating in most people.
Gustatory sweating occurs around the lips and mouth when ingesting foods and beverages that are spicy or hot in temperature. There is no known cause in most cases, but gustatory sweating can be increased in diabetic neuropathy, facial herpes zoster, cervical sympathetic ganglion invasion, central nervous system injury or disease, or parotid gland injury. In the case of parotid gland injury, surgery, infection, or trauma may disrupt parotid gland innervation and lead to regrowth of parotid parasympathetic fibers into sympathetic fibers innervating local sweat glands in skin where the injury took place, usually over the parotid gland. This condition is called Frey syndrome. Asymmetric sweating can be caused by a neurologic abnormality.
Other causes of focal sweating include pretibial myxedema (shins), hypertrophic osteoarthropathy (palms), blue rubber bleb nevus syndrome, and glomus tumor (over lesions). Compensatory sweating is intense sweating after sympathectomy.
Generalized sweating
Generalized sweating involves most of the body. Although most cases are idiopathic, numerous conditions can be involved (see table Some Causes of Generalized Sweating).
Some Causes of Generalized Sweating
Type |
Examples |
|
Cancer* |
|
|
Central nervous system |
Trauma, autonomic neuropathy |
|
Drugs |
Antidepressants, aspirin, nonsteroidal anti-inflammatory drugs, hypoglycemic agents, caffeine, theophylline; opioid withdrawal |
|
Endocrine disorders |
Hyperthyroidism, hypoglycemia, excessive secretion of sex hormones caused by gonadotropin-releasing hormone (GnRH) agonists |
|
Idiopathic |
— |
|
Infections* |
Tuberculosis, endocarditis, systemic fungal infections |
|
Other |
Carcinoid syndrome, pregnancy, menopause, anxiety |
|
* Primarily nocturnal generalized sweating (night sweats). |
|
Symptoms and Signs
Diagnosis
Hyperhidrosis can be primary or secondary to an underlying medical condition. It is diagnosed by history and examination but can be confirmed with the iodine and starch test. For this test, iodine solution is applied to the affected area and allowed to dry. Cornstarch is then dusted on the area, which makes areas of sweating appear dark. Testing is necessary only to confirm foci of sweating (as in Frey syndrome, or to locate the area needing surgical or botulinum toxin treatment) or in a semiquantitative way when following the course of treatment. Asymmetry in the pattern of sweating suggests a neurologic cause.
Treatment
Initial treatment of focal and generalized sweating is similar.
Aluminum chloride hexahydrate 6 to 20% solution in absolute ethyl alcohol is indicated for topical treatment of axillary, palmar, and plantar sweating; these preparations require a prescription. The solution precipitates salts, which block sweat ducts. It is most effective when applied nightly and should be washed off in the morning. Sometimes an anticholinergic drug is taken before applying to prevent sweat from washing the aluminum chloride away. Initially, several applications weekly are needed to achieve control, then a maintenance schedule of once or twice a week is followed. If treatment under occlusion is irritating, it should be tried without occlusion. This solution should not be applied to inflamed, broken, wet, or recently shaved skin. High-concentration, water-based aluminum chloride solutions may provide adequate relief in milder cases.
Glycopyrronium 2.4% cloth wipes can be used to treat primary axillary hyperhidrosis (1). Caution should be used in patients who are sensitive to anticholinergic drug effects.
Tap-water iontophoresis, in which salt ions are introduced into the skin using electric current, is an option for patients unresponsive to topical treatments. The affected areas (typically palms or soles) are placed in tap-water basins each containing an electrode across which a 15- to 25-mA current is applied for 10 to 20 minutes. This routine is done daily for 1 week and then repeated weekly or bimonthly. Iontophoresis may be made more effective by dissolving anticholinergic tablets (eg, glycopyrrolate) into the water of the iontophoresis basins. Although the treatments are usually effective, the technique is time-consuming and somewhat cumbersome, and some patients tire of the routine.
Oral anticholinergic drugs may help some patients. Glycopyrrolate or oxybutynin can be used to decrease sweating but can be limited by anticholinergic adverse effects, including dry mouth, dry skin, flushing, blurred vision, urinary retention, mydriasis, and cardiac arrhythmias.
Botulinum toxin type A is a neurotoxin that decreases the release of acetylcholine from sympathetic nerves serving eccrine glands. Injected directly into the axillae, palms, or forehead, botulinum toxin inhibits sweating for about 5 months depending on dose. Of note, botulinum toxin is approved by the U.S. Food and Drug Administration only for axillary hyperhidrosis and may not be covered by insurance for other sites of hyperhidrosis. Complications include local muscle weakness and headache. Injections are effective but painful and expensive, and treatment must be repeated 2 to 3 times per year.
A microwaved-based device (eg, miraDry®) heats and subsequently permanently destroys sweat glands. Patients may benefit from two treatments at least 3 months apart.
Surgery is indicated if more conservative treatments fail. Patients with axillary sweating can be treated with surgical excision of axillary sweat glands through open dissection or by liposuction (the latter appears to have lower morbidity). Patients with palmar sweating can be treated with endoscopic transthoracic sympathectomy. The potential morbidity of surgery must be considered, especially in sympathectomy. Potential complications include phantom sweating (a sensation of sweating in the absence of sweating), compensatory hyperhidrosis (increased sweating in untreated parts of the body), gustatory sweating, neuralgia, and Horner syndrome. Compensatory hyperhidrosis is most common after endoscopic transthoracic sympathectomy, developing in up to 80% of patients, and can be disabling and far worse than the original problem.
Treatment reference
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1. Glaser DA, Hebert AA, Nast A, et al: Topical glycopyrronium tosylate for the treatment of primary axillary hyperhidrosis: Results from the ATMOS-1 and ATMOS-2 phase 3 randomized controlled trials. J Am Acad Dermatol pii: S0190-9622(18)32224-2, 2018. doi: 10.1016/j.jaad.2018.07.002.
Key Points
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Asymmetric hyperhidrosis suggests a neurologic cause.
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Although diffuse sweating is usually normal, consider cancer, infection, and endocrine disorders as directed by patient symptoms.
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Obtain laboratory tests to determine systemic causes based on clinical findings.
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Treat using aluminum chloride solutions, tap-water iontophoresis, topical glycopyrronium, oral glycopyrrolate or oxybutynin, botulinum toxin, or a microwaved-based device.
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Consider surgical options in patients who do not respond to drug or device therapy; these include excision of axillary sweat glands and endoscopic transthoracic sympathectomy for palmar sweating, which carries risk of significant adverse effects.
