N. Solish, MD, FRCPC and C. Murray, MD, FRCPC

Department of Medicine, University of Toronto, Toronto, Canada

Hyperhidrosis is characterized by sweating in excess of the physiological needs to maintain thermal homeostasis. No formal definition exists but for practical purposes any degree of sweating that interferes with activities of daily living, can be viewed as hyperhidrosis. The cause is unknown, however treatment options do exist. This disease is much more common than once thought and greatly impacts upon quality of life (QOL). Treating these patients can be exceptionally rewarding both for the patient and the physician.

Topical Treatment Controls mild disease
Botulinum Toxin A (BTX-A) Effective [Naumann M, Hamm H, Lowe NJ. Br J Dermatol 147:1-9 (2002a); Naumann M,
Lowe NJ, Kumar CR, Hamm H. Arch Dermatol 139:731-6 (2003); Lowe NJ, Yamauchi PS,
Lask GP, Patnaik R, et al. Dermatol Surg 28(9):822-7 (2002).]
Iontophoresis Effective [Reinauer S, Neusser A, Schauf G, Hölzle E. Br J Dermatol 129:166-9 (1993).]
Surgery Considered only after all other options have failed due to potential complications.
[Zacherl J, Huber ER, Imhof M, et al. Eur J Surg 580(suppl):S43-6 (1998).]
Table 1:   Treatment options for hyperhidrosis

Epidemiology and Etiology

In a recent survey of 150,000 households in the US, 2.8% of the population reported having unusual or excessive sweating.[Strutton DR, Kowalski JW, Glaser DA, Stang PE. Presented at the American Academy of Dermatology 61st Annual Meeting, San Francisco CA.] The axilla is the most common affected site, followed by the feet, palms and face. No gender differences were noted and onset typically occurred during childhood or adolescence. The exact cause of focal hyperhidrosis is unknown, although sympathetic overstimulation of normal eccrine glands is the most likely etiology. Interestingly, studies have shown an association between the sympathetic hyperactivity seen in hyperhidrosis with other autonomic disorders such as cardiac hyperexcitability. There is likely also a heritable component to this neurogenic overactivity, as 30%-50% of patients have a positive family history.[Haider A, Solish N. CMAJ 172(1):69-75 (2005 Jan 4).]

Impact on Quality of Life

Hyperhidrosis has a profound impact on social interactions and work related activities. Routine social interactions such as holding hands, shaking hands or hugging become awkward. Patients report a sense of humiliation and embarrassment associated with soaked or stained clothing as well as perceived odours.[Naumann M, Hamm H, Lowe NJ. Br J Dermatol 147:1-9 (2002a); Haider A, Solish N. CMAJ 172(1):69-75 (2005 Jan 4).]

Drugs/Toxins Alcoholism, substance abuse
Cardiovascular Heart failure, shock
Respiratory Failure
Neurologic Parkinson’s disease, spinal cord injury, cerebrovascular accident
Endocrine Hyperthryroidism, diabetes mellitus, pheochromocytoma,
carcinoid syndrome, acromegaly,
pregnancy, menopause
Infections
Malignancies Hodgkin’s disease, myeloproliferative disorders
Table 3:   Etiology of secondary hyperhidrosis

Diagnosis and Patient Evaluation

A history focussing on the location of excessive sweating, duration of the presentation, associated symptoms or comorbidities, family history, age of onset and any specific triggers allows one to differentiate primary from secondary hyperhidrosis. The physical exam will be guided by any suggestion of secondary hyperhidrosis, and will also attempt to confirm the distribution of disease.

Measurement of Hyperhidrosis

Each evaluation should attempt to determine the volume of sweat production, the distribution of hyperhidrosis and the affect on QOL. The starch iodine test provides a qualitative assessment of both volume of sweat production and extent of distribution.

  • The area to be tested is dried and an iodine solution (1%-5%) is applied.
  • After a few seconds, starch is sprinkled over this area.
  • The starch and iodine interact in the presence of sweat to develop a purplish sediment.
Hyperhidrosis Type Clinical Presentation
Primary (idiopathic) Focal – localized to the axillae, palms, feet, face
Secondary Generalized, though it can present in a localized, focal pattern.
Table 2:   Clinical Presentation of hyperhidrosis

This test is most helpful when delineating the area for treatment. To assess impact on QOL, various measures have been validated, such as the hyperhidrosis disease severity scale (HDSS). (Table 2)

Topical Treatments for Hyperhidrosis

Aluminum chloride hexahydrate is considered to be the most effective topical agent for focal, mild axillary hyperhidrosis. It works through mechanical obstruction of the eccrine sweat gland pore. Another topical product is glycopyrrolate, a topical anticholinergic product available as topical pads for mild cases. The main limiting side-effects of all of these products are skin irritation, lack of efficacy in moderate-to-severe axillary hyperhidrosis, and poor response on the palms and soles.

My sweating is never noticeable and never interferes with my daily activities. Score 1
My sweating is tolerable but sometimes interferes with my daily activities. Score 2
My sweating is barely tolerable and frequently interferes with my daily activities. Score 3
My sweating is intolerable and always interferes with my daily activities. Score 4
Table 4:   Hyperhidrosis Disease Severity Scale (HDSS) is a four-point scale to determine the degree of severity of hyperhidrosis.

Systemic Treatments

In addition to glycopyrrolate mentioned in Table 5, other agents such as clonazepam, diltiazem, clonidine and nonsteroidal anti-inflammatories have been reported to be useful in isolated cases.

TREATMENT INDICATION COMMENTS
Topical treatments Axillary, facial, less commonly palmar and plantar hyperhidrosis Short term action. Efficacy in mild cases. Major side effect is local irritation. Palms and soles less responsive
Systemic treatments, e.g., glycopyrrolate Main role in generalized and compensatory hyperhidrosis. Limited efficacy due to anticholinergic side-effects, e.g., dry mouth, blurred vision, constipation, urinary retention, palpitations.
Iontophoresis Palmar and plantar hyperhidrosis Well tolerated. Dryness and irritation are common. Efficacy can reach 90%. Major limitations are the equipment expense and procedure is time consuming
Surgical sympathectomy Hyperhidrosis unresponsive to topical or systemic treatment and BTX-A Major limitation is possible surgical adverse events and an unacceptable high rate of compensatory hyperhidrosis. ETS surgery should be considered as a last resort.
Botulinum toxin injections Axillary, palmar, plantar and facial hyperhidrosis Commonly used for moderate-to-severe disease or if mild cases do not respond to topical treatment. Safe, effective and well-tolerated treatment with excellent patient satisfaction. Drug usually covered by third party insurance.
Table 5:   Hyperhidrosis treatment options

Treatments Considerations with Botulinum Toxin

The main contraindications to botulinum toxin therapy include neuromuscular disorders such as myasthenia gravis, pregnancy and lactation, organic causes of hyperhidrosis, and medications that may interfere with neuro-muscular transmission. [Haider A, Solish N. CMAJ 172(1):69-75 (2005 Jan 4).] Appropriate selection of patients is essential to ensure a satisfactory treatment response and avoid unnecessary frustrations.

Condition Results Side-effects Comments
Axillary hyperhidrosis [Naumann M, Hamm
H, Lowe NJ. Br J Dermatol 147:1-9 (2002a); Naumann M, Lowe NJ, Kumar CR, Hamm H. Arch Dermatol 139:731-6 (2003); Solish N, Benohanian A, Kowalski JW. Dermatol Surg
31(4):405-13 (2005 Apr).]
>90% response rates with statistically significant improvements QOL Safe, well tolerated Typical starting doses are 50 units of BTX-A per axilla. The mean duration of effect is 6–7 months.
Palmar hyperhidrosis [Lowe NJ, Yamauchi PS, Lask GP, Patnaik R, et al. Dermatol Surg 28(9):822-7 (2002).] >90% response rates Pain at the site of injection; transient minor
weakness of intrinsic hand muscles lasting 2-5 wks.
Treatment consists of 100 units per palm. Intradermal injection into the palm is painful, so anesthesia is strongly recommended.
Regional nerve blockade (median and ulnar) is most commonly used. Topical anesthesia is ineffective.
Plantar hyperhidrosis [Haider A, Solish N. CMAJ 172(1):69-75 (2005 Jan 4).] Excellent response rates have been reported Pain at the site of injection Treatment doses and technique are similar to the palms, occasionally requiring a higher dose.
Regional nerve block is generally required for anaesthesia and involves the posterior tibial and aural nerves. Duration of effect is 4-6 months.
Facial hyperhidrosis [Haider A, Solish N. CMAJ 172(1):69-75 (2005 Jan 4).] Clinically significant improvements seen Forehead is most common affected area with the main site of injection being a band along the hairline, extending into the temporal scalp. Can also involve the upper lip, nasolabial folds, malar regions. Duration of effect is 5-6 months.
Table 6:   Review of BTX-A treatment to focal areas.