Excessive sweating

Hyerhidrosis is the excessive production of sweat.

Sweat is produced (secreted) by appendages of the skin. Two different types of sweat glands can be distinguished: eccrine and apocrine glands. Eccrine glands can be found anywhere on the body, although they are more numerous around the palms, the soles of the feet and the armpits (axillary space). Apocrine glands predominate in the axillary and genital areas (prepuce, labia majora and areola).

The production and excretion of sweat are mediated by the sympathetic nervous system and regulated by the hypothalamus (a cerebral gland). Eccrine glands play an important role in the regulation of body temperature. Under the effect of stress or heat, they can secrete up to 10 litres of sweat daily. As for the apocrine glands, they produce an odourless liquid which, when decomposed by the action of bacteria, acquires a characteristic, unpleasant smell.

Eccrine sweating is a normal process in response to increased body temperature (hot weather, exercise, fever) or emotion.

Hyperhidrosis can be primary or "essential" (without known cause) or secondary (as part of an underlying condition). Localized hyperhidrosis (hands, feet or armpits) is mostly essential, the cause of the condition can not be determined. Hyperhidrosis involving the whole body or localized in an unusual area (other than the hands, feet or armpits) requires medical assessment, especially if it has appeared recently.

Essential or primary hyperhidrosis may be due to an excessive activity of the reflex arcs involved in eccrine sweating. Familial hyperhidrosis is not uncommon but its transmission process is poorly understood. Essential hyperhidrosis often appears at puberty and culminates between the 3rd and 4th decades, before decreasing with age. Palmoplantar (hands and feet) hyperhidrosis is most common in men. It is mostly intermittent and majored by stress. A vicious circle starts when the excessive sweating of hands or armpits becomes embarrassing to the patient and generates a stress which worsens the condition. Excessive sweating is a distressing aesthetic issue and can become a paralyzing disability. Patients with axillary hyperhidrosis can see their clothes fade and deteriorate. Plantar hyperhidrosis promotes bacterial proliferation and accelerates shoe deterioration. Hyperhidrosis of the hands is the most disabling form of the disorder as patients can experience social discomfort, be reluctant to shake hands or touch paper documents.

Localized hyperhidrosis

Aluminium chloride

Aluminium chloride hexahydrate is the topical treatment of reference for hyperhidrosis. Several firms market this product as liquid or cream "antiperspirant" or "long-acting deodorant". At the usual concentrations (10 to 20%), aluminium chloride products (Etiaxil®, PM®, Dove®, etc.) can stop normal or slightly excessive sweating; they are however ineffective on more severe hyperhidrosis. These products are irritants, they must be used on carefully dried armpits and their use must be discontinued in case of burns or irritation (frequent). Dr Benohanian recommends aluminium chloride-based preparations (30 to 50%) containing salicylic acid to patients suffering from palmar or plantar hyperhidrosis. In France, however, manufacturing these preparations remains difficult.

Rumour has it that aluminium may induce severe disease such as breast cancer, although scientific studies have so far found no evidence of this. Dr Philippa Darbre seems to have been at the origin of this theory: she was convinced of the potential role of deodorants in breast cancer after observing high paraben levels in mammary tissue.

Iontophoresis

Iontophoresis is the second intention treatment of moderate palmoplantar hyperhidrosis (after failure of concentrated aluminium chloride preparations), it requires costly equipment (200 to 1,000 euros). Iontophoresis on the axillary space is more difficult to implement. The mechanism of action of this technique on perspiration remains poorly understood. It is based on the therapeutic use of electrical current. The hands/feet to be treated are plunged in water through which runs an electrical current. The treatment protocols are individualized according to the equipment used and the patient to treat. The initial treatment usually involves three to five 10-minutes sessions weekly until a satisfying result is obtained. Maintenance sessions are then required two to three times a week. Iontophoresis treatment is rather demanding but often effective. Several theories have been formulated in order to explain its efficacy; some suggest it could be due to the obstruction of sweat gland ducts. Iontophoresis is harmless (when well conducted), effective and well tolerated. Patients are advised to first try out the treatment at a practice (dermatologist, kinesitherapist) before buying costly equipment. The treatment technique is also difficult to master and training is therefore needed in order to avoid complications (burns).

Botox

Type A botulinum toxin is a fast, harmless and very effective treatment of axillary hyperhidrosis resistant to aluminium chloride. The interest of type A botulinum toxin in the treatment of excessive sweating has been suggested since 1994; recent scientific articles have confirmed its efficacy. Its use has however been limited by the high cost of the product (250 to 300 euros for a 100-unit vial) on top of which must be added the practitioner’s fees. Botox treatment is contra-indicated in patients suffering with myasthenia or amyotrophic lateral sclerosis, as well as in patients taking certain antibiotics (aminoglycosides), and in pregnant or breastfeeding women. Botox® was recently given approval in this indication by the French sanitary authorities (AFSSAPS, Agence française de sécurité sanitaire des produits de santé).

Botox treatment is mostly beneficial to patients suffering with axillary hyperhidrosis. Firstly, the practitioner identifies the worst affected area by performing an iodine test (an iodine solution is applied under the armpit, followed by starch; the sweating areas take a blue coloration). The practitioner then delineates 2cm squares in the corners of which very small quantities of botulinum toxin are injected. Ten injections are generally performed on each armpit. The injections cause little pain as they are conducted on a superficial level with an extremely fine needle. Sensitive patients can benefit from a topical anaesthesia with an EMLA cream. The effect starts being felt two days after the injections, the action of the treatment gradually increases and reaches peak efficacy after one month. The duration of action varies according to the patient, the toxin’s concentration and the total injected dose. Injection of 50 units of botulinum toxin in each armpit (i.e. half a vial of Botox® or Vistabel®) stops sweating in 96.1 % of patients for a duration of 7 months (see bibliography ref. n°1). Injections must be repeated at regular intervals as the treatment’s effects are temporary.

Botulinum toxin injections are effective on hands and feet; however a number of issues render them delicate to use. The specialized anaesthesia sometimes required must be performed in a clinical setting and increases the cost of treatment (already high). The cost of treatment is also made prohibitive by the lage doses needed to treat wide areas of skin. Muscular weakness is a frequent side effect of the treatment, it can sometimes be disabling.

Botox can be used in the treatment of refractory localized hyperhidrosis such as that occurring after parotide surgery (Frey’s syndrome).

Surgery

Surgical excision of axillary eccrine sweat glands
This is an effective, permanent, simple and harmless solution for the treatment of disabling axillary hyperhidrosis unresponsive to medical treatment. The surgeon removes a large portion of the axillary skin, including the underlying apocrine glands. This procedure leaves a large, permanent Z-shaped scar. Skin-conserving techniques (liposuction, ablation of subcutaneous tissues) are less effective.

Endoscopic transthoracic sympathectomy.
This procedure can be considered in patients with very disabling palmar hyperhidrosis resistant to medical treatment. Results are permanent but complications and adverse effects can arise. The complications inherent to the surgery and anaesthesia are well documented, they are rare or very rare and of various severity (nerve block 0.5%, hemothorax and pneumothorax 0.3%, etc. See bibliography ref n°3). Compensation hyperhidrosis (chest, back, thighs) is the most common adverse effect, it affects a third of patients and is impossible to predict; compensation hyperhidrosis can be minimal, moderate (a third of cases) or very disabling (1% of cases).

Treatment guidelines for localized hyperhidrosis

	Option 1	Option 2	Option 3	Option 4
Palmar hyperhidrosis	Aluminium chloride 20 to 40% with or without 4% salycilic acid (Etiaxil® or formulation)	Iontophoresis	Type A botulinum toxin	Endoscopic transthoracic sympathectomy
Plantar hyperhidrosis	Aluminium chloride 20 to 40% with or without 4% salycilic acid (Etiaxil® or formulation)	Iontophoresis	Type A botulinum toxin
Axillary hyperhidrosis	Aluminium chloride 20% (Etiaxil®, PM cream®)	Type A botulinum toxin	Iontophoresis	Surgical excision of axillary eccrine sweat glands
Localized hyperhidrosis (Frey’s syndrome, Ross syndrome)	Aluminium chloride 20 to 40% with or without 4% salicylic acid (Etiaxil® or formulation)	Type A botulinum toxin

Generalized hyperhidrosis

Medical treatment
Drugs that stop perspiration can be useful in some cases (anticholinergics such as oxybutynin, propanthelin or benztropine). However, the doses needed to stop excessive sweating often induce adverse effects more disabling than the hyperhidrosis itself. They are therefore seldom used. In specific cases, tranquillizers, beta-blockers, calcium channel blockers, non steroidal anti-inflammatory drugs or other molecules can be used. The treatments used in localized hyperhidrosis can also be used in generalized hyperhidrosis on a limited area of more excessive sweating.

Antranik Benohanian MD, FRCP
Information on hyperhidrosis and its treatments by a Canadian dermatologist (Montreal).

Hyperhidrosis
Exhaustive information on hyperhidrosis; by Dr Anthanik Benohanian MD, FRCP.

Excessive sweating
How to treat excessive sweating, what’s new, find a doctor in Canada, discussion forum.

International Hyperhidrosis Society
Understanding hyperhidrosis, treatment options, working with a doctor, news and research as well as a physician finder. A section is devoted to health care professionnals.

Manufacturers/providers of Iontophoresis equipment
• I2M – 16 bis Fossé-Saint-Julien, BP 200, 14011 Caen Cedex. Phone : 02 31 50 29 30. This company provides patients with a list of practitioners using these equipments.
• Ionomat – 34260 La Tour-sur-Orb. Phone : 04 67 23 78 73. Fax : 04 67 23 79 23.
• Drionic – battery-powered Iontophoresis equipment.

1. Naumann M., Lowe N.J., Kumar C.R. et al. Botulinum toxin type a is a safe and effective treatment for axillary hyperhidrosis over 16 months: a prospective study. Arch. Dermatol. 2003; 139: 731-6.
ABSTRACT
Objective: To evaluate the safety and efficacy of botulinum toxin type A (BTX-A) (Botox) over 16 months in the treatment of bilateral primary axillary hyperhidrosis.
Design: a 16-month study with initial double-blind randomization to 50 U of BTX-A or placebo per axilla. After 4 months, participants could receive up to 3 further treatments with open-label BTX-A over 12 months.
Setting: fourteen dermatology or neurology clinics in Germany, Belgium, and the United Kingdom.
Participants: of 207 individuals aged between 17 and 74 years who had persistent bilateral primary axillary hyperhidrosis that interfered with daily activities, 174 (84 %) completed the study. The baseline gravimetric assessment was a spontaneous sweat production of 50 mg or greater in each axilla prior to initial treatment.
Main Outcome Measures: at week 4 after each treatment, the response rate of subjects who had at least a 50 % reduction from baseline in axillary sweating, as measured by gravimetric assessment, was evaluated. Adverse events were spontaneously reported throughout the study, together with quality-of-life parameters and assessment of neutralizing antibodies to BTX-A.
Results: over the 16-month period, 356 BTX-A treatments were given to 207 subjects. After placebo treatment, the response rate at week 4 was 34.7 %. After the first, second, and third treatment with BTX-A, response rates at week 4 were 96.1 %, 91.1 %, and 83.3 %, respectively. For subjects receiving more than 1 treatment, the mean duration between BTX-A treatments was approximately 7 months; however, 28 % of subjects completed the study after only 1 BTX-A treatment. Subjects’ satisfaction after treatments was consistently high, their quality of life improved, and there was a reduction in the impact of the disease on their lives. The safety profile of BTX-A after repeated treatments was excellent and no confirmed positive results for neutralizing antibodies to BTX-A occurred.
Conclusion: repeated intradermal injections of BTX-A over 16 months for treatment of primary axillary hyperhidrosis is safe and efficacious.
2. Lowe P.L., Cerdan-Sanz S., Lowe N.J. Botulinum toxin type A in the treatment of bilateral primary axillary hyperhidrosis: efficacy and duration with repeated treatments. Dermatol Surg 2003; 29: 545-8.
3. Heckmann M., Teichmann B., Pause B.M. et al. Amelioration of body odor after intracutaneous axillary injection of botulinum toxin A. Arch Dermatol 2003; 139: 57-9.
4. Belin E.E., Polo J. Treatment of compensatory hyperhidrosis with botulinum toxin type A. Cutis 2003; 71: 68-70.
5. Kreyden O.P., Böni R., Burg G. Hyperhidrosis and botulinum toxin in dermatology, Vol. 30. Zurich: Karger, 2002.
6. Heckmann M. Hyperhidrosis of the axilla. Curr Probl Dermatol 2002; 30: 149-55.
7. Heckmann M., Schaller M., Breit S. et al. Evaluation of therapeutic success of hyperhidrosis therapy. Arch Dermatol 2001; 137: 94.
8. Heckmann M., Ceballos-Baumann A.O., Plewig G. Botulinum toxin A for axillary hyperhidrosis (excessive sweating). N Engl J Med 2001; 344: 488-93.