AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Hyperhidrosis, which is sweating in excess of that required for normal thermoregulation, is a condition that usually begins in either childhood or adolescence. Although any site on the body can be affected, the sites most commonly affected are the palms, soles, and axillae. This condition may be idiopathic or secondary to other diseases, metabolic disorders, febrile illnesses, or medication use. Hyperhidrosis exists in 3 forms: emotionally induced (in which it affects the palms, soles, and axillae), localized, or generalized. The condition often causes great emotional distress and occupational disability for the patient, regardless of the form.

A related Medscape CME course is MedsiteCME: Neurotoxin Injection Therapy in a Patient With Primary Axillary Hyperhidrosis.

Pathophysiology

Generalized hyperhidrosis may be the consequence of autonomic dysregulation, or it may develop secondary to a metabolic disorder, febrile illness, or malignancy. In its localized form, hyperhidrosis may result from a disruption followed by abnormal regeneration of sympathetic nerves or a localized abnormality in the number or distribution of the eccrine glands, or it may be associated with other (usually vascular) abnormalities.

Essential hyperhidrosis, a disorder of the eccrine sweat glands, is associated with sympathetic overactivity.¹ It does not appear to be a generalized disorder involving vascular endothelium.

Frequency

United States

In adolescents and young adults, an incidence of 0.6-1.0% is reported.²

International

Palmoplantar hyperhidrosis occurs 20 times more frequently in the Japanese than in any other ethnic group.^{3, 4}

Mortality/Morbidity

• Hyperhidrosis is not associated with mortality.
• Severe cases of hyperhidrosis may adversely affect the patient's quality of life (see Complications).

Race

All races can be affected; however, Japanese are reportedly affected more than 20 times more frequently than other ethnic groups.^{3, 4}

Sex

Both sexes can be affected by hyperhidrosis.

Age

• Persons of all ages can be affected by hyperhidrosis.
• Localized hyperhidrosis, unlike generalized hyperhidrosis, usually begins in childhood or adolescence. In a study of 850 patients with palmar, axillary, or facial hyperhidrosis, 62% of patients reported that sweating began since before they could remember; 33%, since puberty; and 5%, during adulthood.⁵

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

• Essential hyperhidrosis is a dermatologic and neurologic disorder characterized by excessive sweating of the eccrine sweat glands.⁶

• Patients note excessive sweating in affected areas, which ultimately prompts them to seek medical attention.
• Palmoplantar hyperhidrosis (excessive sweating of the palms and soles) is observed in persons with chronic alcoholism.⁷
• Localized hyperhidrosis, unlike generalized hyperhidrosis, usually begins in childhood or adolescence.
• Hyperhidrosis beginning later in life should prompt a search for secondary causes such as systemic diseases, adverse effects of medication use, or metabolic disorders.
• Harlequin syndrome is characterized by unilateral hyperhidrosis and flushing, predominantly induced by heat or exercise.⁸ The sympathetic deficits are usually limited to the face.
• An echo-Doppler study found impaired left ventricular filling in patients with essential hyperhidrosis, which is associated with cardiac autonomic dysfunction because sympathetic fibers to eccrine glands of the palms of the hand arise from stellate and upper thoracic ganglia, which also innervate the heart.⁶ This study indicated that hyperactivity of the sympathetic nervous system in patients with hyperhidrosis may alter cardiac function in the long term.
• The temperament and character profile for patients with essential hyperhidrosis has stimulated interest,⁹ but recent data suggest that hyperhidrosis is not related to social phobia or personality disorder.

Physical

• Visible signs of hyperhidrosis are clearly evident.
• If direct visualization of the affected areas is desired, the iodine starch test may be used.
• • This test requires spraying of the affected area with a mixture of 0.5-1 g of iodine crystals and 500 g of soluble starch.
  • Areas that produce sweat will turn black.

Causes

Hyperhidrosis may be idiopathic or secondary to other diseases, metabolic disorders, febrile illnesses, or medication use.

• Generalized hyperhidrosis may be secondary to numerous conditions including the following:
• • Neurologic or neoplastic diseases
  • Metabolic disorders or processes (eg, thyrotoxicosis, diabetes mellitus, hypoglycemia, gout, pheochromocytoma, menopause)
  • Febrile illnesses
  • Use of medications (eg, propranolol, physostigmine, pilocarpine, tricyclic antidepressants, venlafaxine)
  • Chronic alcoholism
  • Hodgkin disease or tuberculosis (in nocturnal hyperhidrosis)
• Localized hyperhidrosis may be emotionally induced and usually affects the palms, soles, and/or axillae. Unlike sweating on the remainder of the body, sweating on the palms and soles is controlled solely by the cerebral cortex and is responsive to emotional stimuli rather than to temperature stimuli.¹⁰ Both emotional and thermoregulatory stimuli control sweating in the axillae; therefore, palmoplantar hyperhidrosis, unlike generalized hyperhidrosis, does not occur during sleep or sedation.
• Localized hyperhidrosis may also be associated with the following:
  • Gustatory stimuli (associated with Frey syndrome, encephalitis, syringomyelia, diabetic neuropathies, herpes zoster parotitis, and parotid abscess)
  • Eccrine nevus
  • Eccrine angiomatous hamartoma
  • Blue rubber-bleb nevus
  • Glomus tumor
  • Peripheral neuropathy, organomegaly, endocrinopathy, monoclonal plasma-proliferative disorder, and skin changes (POEMS) syndrome
  • Burning feet syndrome
  • Pachydermoperiostosis
  • Pretibial myxedema

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Burning feet syndrome
Neoplastic diseases
Neurologic diseases
Thyrotoxicosis
Diabetes mellitus
Hypoglycemia
Gout
Pheochromocytoma
Menopause
Febrile illnesses
Use of medications (eg, propranolol, physostigmine, pilocarpine, tricyclic antidepressants, venlafaxine)
Chronic alcoholism
Hodgkin disease
Tuberculosis
Eccrine nevus
Eccrine angiomatous hamartoma
Riley-Day syndrome (familial dysautonomia)

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Search for primary causes if generalized hyperhidrosis is noted.
• Important laboratory studies may include the following:
• • Thyroid function tests may reveal underlying hyperthyroidism or thyrotoxicosis.
  • Blood glucose levels may reveal diabetes mellitus or hypoglycemia.
  • Urinary catecholamines may reveal a possible pheochromocytoma.
  • Uric acid levels may reveal gout.
  • A purified protein derivative (PPD) test can be performed to screen for tuberculosis.

Imaging Studies

• Chest radiography may be used to rule out tuberculosis or a neoplastic cause.

Histologic Findings

Individuals with hyperhidrosis have morphologically and functionally normal eccrine glands. Localized hyperhidrosis may result from an abnormal number and/or distribution of otherwise normal eccrine glands. Examples of such conditions include eccrine nevus and eccrine angiomatous hamartoma.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

Therapy can be challenging for both the patient and the physician. Both topical and systemic medications have been used. Other treatment options include iontophoresis and botulinum toxin injections.

• Topical agents include topical anticholinergics, boric acid, 2-5% tannic acid solutions, resorcinol, potassium permanganate, formaldehyde (which may cause sensitization¹¹), glutaraldehyde, and methenamine. Drysol (20% aluminum chloride hexahydrate in absolute anhydrous ethyl alcohol) is usually the most effective 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.¹⁰
• Systemic agents used to treat hyperhidrosis include anticholinergic medications. Anticholinergics such as propantheline bromide, glycopyrrolate, oxybutynin, and benztropine are effective because the preglandular neurotransmitter for sweat secretion is acetylcholine (although the sympathetic nervous system innervates the eccrine sweat glands). 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.¹² 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.¹³ 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.¹³ 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.¹⁴
• 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. See Botulinum Toxin for more information.
• • 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.¹⁵ 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.¹⁶
  • In a similar study, the effects of sodium chloride solution injections in one palm were compared with botulinum toxin injections in the other palm.¹⁷ 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.¹⁸ 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.¹⁹

Surgical Care

In addition to pharmacologic therapy, other treatments include surgical sympathectomy, surgical excision of the affected areas, and subcutaneous liposuction. Each modality has been used effectively.

Palmar hyperhidrosis is a benign functional disorder that is a psychological and social handicap.²⁰ 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.²¹ Sympathectomy involves the surgical destruction of the ganglia responsible for hyperhidrosis.
• • 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. Recently, 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.⁵ 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 T4.²²
  • 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.⁵ In a similar study²³ 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%.
    • T4 ganglion interruption for palmar hyperhidrosis is an effective approach that can simultaneously minimize the rate of compensatory hyperhidrosis.²⁴ 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.²⁵
    • Topical glycopyrrolate application may be effective and safe for the treatment of excessive facial sweating in primary craniofacial and secondary gustatory hyperhidrosis following sympathectomy.²⁶
• 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.²⁷
• 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.²⁸

Consultations

Consult a neurosurgeon if sympathectomy is necessary in severe cases of hyperhidrosis that are refractory to all other treatments.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

The goals of pharmacotherapy are to reduce morbidity and prevent complications. Control of palmar hyperhidrosis with a new dry-type iontophoretic device has been described.²⁹ Dry-type iontophoresis may reduce palmar sweating more conveniently than other conventional methods.

Drug Category: Aldehydes

These agents reduce perspiration by denaturing keratin and thereby occluding the pores of the sweat glands. They have a short-lasting effect. Contact sensitization is increased, especially with formalin. Aldehydes are used to treat the palms and soles; they are not as effective in the axillae.

Drug Category: Aluminum compounds

These agents are antiperspirants that are used in the management of hyperhidrosis.

Drug Category: Anticholinergic agents

The use of these agents is usually avoided because they are poorly tolerated at the required doses when given systemically. Acetylcholine is the preglandular neurotransmitter for sweat secretion. These drugs inhibit the binding of acetylcholine to the cholinergic receptor. Clinical effects usually occur within days.

Drug Category: Neuromuscular blocking agents

These agents inhibit the transmission of nerve impulses at the neuromuscular junction of skeletal muscle and/or autonomic ganglia.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Sympathectomy requires an inpatient stay.

Further Outpatient Care

• Many of the treatment options require repeat visits to the dermatologist for continuing care (eg, repeated botulinum injections, refill prescriptions) and for evaluating therapeutic progress.

Complications

• Severe cases of hyperhidrosis may adversely affect the patient's quality of life by causing great emotional distress, social embarrassment, and work-related disability (due to palmoplantar hyperhidrosis).
• Palmoplantar sweating may result in irritation of the affected skin, ultimately leading to chafing.
• Axillary hyperhidrosis may be malodorous, causing social embarrassment. 

Prognosis

• Hyperhidrosis is difficult to treat effectively.
• With the newer treatment modalities now available, the patient has numerous options and is offered a better prognosis.

Patient Education

• Patients should be educated regarding all of the treatment options, including their corresponding complications and costs.
• For excellent patient education resources, visit eMedicine's Procedures Center. Also, see eMedicine's patient education article BOTOX® Injections.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• The failure to search for systemic causes for hyperhidrosis with an onset later in life is a pitfall.
• The failure to search for systemic causes of generalized hyperhidrosis is a pitfall.
• The failure to recognize underlying conditions is a pitfall that may result in unnecessary patient discomfort and ineffective treatment. Correction of underlying conditions may resolve hyperhidrosis.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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Article Last Updated: May 2, 2008