generalized hyperhidrosis

Generalized hyperhidrosis

Generalized hyperhidrosis is the name given to excessive and uncontrollable sweating that affects large areas of your body with excessive sweating, typically in adults whose sweating occurs during both waking and sleeping hours.

In patients with hyperhidrosis, sweat glands (eccrine glands in particular) overreact to stimuli, producing more sweat than is needed. 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 centimeter). Hyperhidrosis is embarrassing and interferes with many daily activities. Hyperhidrosis negatively impacts daily life, especially emotional well-being, self-esteem, interpersonal relationships, and occupational productivity 1).

Overall, there are two types of hyperhidrosis, both of which may be inherited:

  • Generalized hyperhidrosis: Generalized hyperhidrosis affects most or all of the body.
  • Localized hyperhidrosis: Localized hyperhidrosis affects armpits, palms, soles, face or other sites.

Hyperhidrosis 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
  • More than 90% of hyperhidrosis cases are primary, and more than one-half of these cases affect the armpits (axillae) 2).
  • Primary hyperhidrosis is reported to affect 1–3% of the US population and nearly always starts during childhood or adolescence. Although prevalence between sexes is roughly equal, women are more likely to report hyperhidrosis to their physician 3).
  • More than one-third of persons with axillary hyperhidrosis report that the condition is barely tolerable or completely intolerable, and it nearly always interferes with daily activities 4).
  • Up to two-thirds of patients report a family history, suggesting a genetic predisposition and it is reported to be particularly prevalent in Japanese people.

Secondary hyperhidrosis

  • Less common than primary hyperhidrosis. Secondary hyperhidrosis is less common and can present at any age.
  • More likely to be unilateral and asymmetrical, or generalized hyperhidrosis
  • Can occur at night or during sleep.
  • Due to endocrine or neurological conditions.

Localized hyperhidrosis affects the palms, soles, armpits and face:

  • Hands (palmar hyperhidrosis);
  • Armpits (axillary hyperhidrosis);
  • Feet (plantar hyperhidrosis)

Unlike generalized hyperhidrosis, localized hyperhidrosis usually begins in adolescence, but can also manifest in childhood or even in infancy. Localized hyperhidrosis typically does not occur during sleep and is commonly caused by:

  • Emotional stress, especially anxiety
  • Heat
  • Certain odors
  • Certain foods, including citric acid, coffee, chocolate, peanut butter and spices
  • Spinal cord injury.

People of all ages and genders can be affected by hyperhidrosis. Hyperhidrosis affects millions of people around the world (approximately 1% to 3% of the U.S. population), but because of lack of awareness and understanding that there are treatments for the condition, more than half of these people are never diagnosed or treated for their symptoms 5).

There are a variety of treatment options for patients with hyperhidrosis. Typically, your physician will initially treat hyperhidrosis with ointments or salves that “dry up” sweat glands.

Antiperspirants, both prescription (such as Drysol) and non-prescription also decrease sweating in not only the armpits, but also can be used to treat mild cases of hyperhidrosis of the hands and feet.

When to contact a medical professional

See your doctor if you have sweating:

  • That is prolonged, excessive, and unexplained.
  • With or followed by chest pain or pressure.
  • With weight loss.
  • That occurs mostly during sleep.
  • With fever, weight loss, chest pain, shortness of breath, or a rapid, pounding heartbeat. These symptoms may be a sign of an underlying disease, such as overactive thyroid.

Generalized hyperhidrosis causes

The cause of primary hyperhidrosis is not well understood 6). Eccrine sweat glands—distributed throughout your body, but heavily concentrated on your palms, soles, armpits (axillae) and face—are innervated by postganglionic autonomic nerve fibers and stimulated by the neurotransmitter acetylcholine 7). It is thought that increased or aberrant sympathetic stimulation of the eccrine sweat glands is responsible for the increased sweating rather than an increased number or size of the glands 8). Persons with primary hyperhidrosis have a higher-than-normal basal level of sweat production and an increased response to normal stimuli, such as emotional or physical stress.

Causes of secondary generalized hyperhidrosis include:

  • Heat, humidity, exercise
  • Infections, such as tuberculosis
  • Febrile illness
  • Cancers (Hodgkin disease or Hodgkin lymphoma, cancer of the lymphatic system)
  • Metabolic diseases and disorders, including:
    • hyperthyroidism (overactive thyroid),
    • diabetes,
    • hypoglycemia,
    • pheochromocytoma (a benign endocrine tumor of the sympathetic nervous system),
    • gout, and
    • pituitary disease (hyperpituitarism).
  • Menopause
  • Obesity
  • Acromegaly
  • Anxiety conditions (e.g., generalized anxiety disorder, social anxiety)
  • Carcinoid syndrome
  • Heart disease, such as heart attack
  • Congestive heart failure
  • Stroke
  • Chronic pulmonary disease; acute respiratory failure
  • Parkinson disease
  • Alcohol use
  • Caffeine
  • Spicy foods
  • Severe psychological stress
  • Spinal cord injury
  • Some prescription drugs e.g., corticosteroids, cholinesterase inhibitors, tricyclic antidepressants, selective serotonin reuptake inhibitors, nicotinamide and opioids
  • Substance abuse; narcotic withdrawal
  • Neurologic (e.g., Arnold-Chiari malformation)
  • Autonomic dysfunction.

Select medications that may cause secondary hyperhidrosis 9):

  • Antidepressants
    • Selective serotonin reuptake inhibitors (e.g., fluoxetine [Prozac])
    • Serotonin-norepinephrine reuptake inhibitors (e.g., venlafaxine)
  • Cholinergic agonists
    • Pilocarpine
    • Pyridostigmine (Mestinon)
  • Hypoglycemics
    • Insulin
    • Sulfonylureas
    • Thiazolidinediones
  • Selective estrogen receptor modulators
    • Raloxifene (Evista)
    • Tamoxifen
  • Miscellaneous
    • Infliximab (Remicade)
    • Niacin
    • Sildenafil (Viagra)

Primary generalized 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

Generalized hyperhidrosis symptoms

Generalized hyperhidrosis is the name given to excessive and uncontrollable sweating that affects large areas of your body with excessive sweating, typically in adults whose sweating occurs during both waking and sleeping hours.

Generalized hyperhidrosis diagnosis

When hyperhidrosis is suspected, your doctor will perform a thorough physical exam. Hyperhidrosis is usually diagnosed clinically.

You may also be asked details about your sweating, such as:

  • Location — Does it occur on your face, palms, or armpits, or all over the body?
  • Time pattern — Does it occur at night? Did it begin suddenly?
  • Triggers — Does the sweating occur when you are reminded of something that upsets you (such as a traumatic event)?
  • Other symptoms — Weight loss, pounding heartbeat, cold or clammy hands, fever, lack of appetite.

Several tests may be performed, including:

  • Starch-iodine test: An iodine solution is applied to the sweaty area and starch is sprinkled over the iodine solution. The starch-iodine combination will turn a dark blue color indicating where there is excess sweat production.
  • Paper test: Special paper is placed on the affected area to absorb sweat, and then weighed to determine the amount of sweating that occurs.
  • Laboratory tests, such as thyroid function tests, blood glucose and uric acid level measurements, and urine samples are performed to rule out more serious medical conditions that may be associated with excessive sweating.
  • Imaging tests may be ordered if a tumor is suspected.

Tests relate to the potential underlying cause of hyperhidrosis and are rarely necessary for primary hyperhidrosis.

Generalized hyperhidrosis treatment

First-line treatment of all primary focal hyperhidrosis, regardless of severity, is topical 20% aluminum chloride (Drysol) 10). This solution is applied nightly to the affected areas for six to eight hours until the Hyperhidrosis Disease Severity Scale score decreases, at which time the application interval can be lengthened to maintain sweat control 11). The aluminum salts cause an obstruction of the eccrine sweat glands and destruction of the secretory cells. This solution can result in skin irritation, but it can be diluted to decrease irritation if necessary. Use of over-the-counter “clinical strength” antiperspirants containing aluminum zirconium trichlorohydrate has shown a decrease in excessive sweating (as measured by sweat production, not the Hyperhidrosis Disease Severity Scale score), with less skin irritation than prescription-strength aluminum chloride solutions 12).

The Hyperhidrosis Disease Severity Scale (HDSS) is a validated single-question survey with four grades of tolerability of sweating and impact on quality of life 13). This survey can estimate the effect on daily activities and response to treatment.

The Hyperhidrosis Disease Severity Scale (HDSS) is scored as follows:

  • 1 point for sweating that is not noticeable and does not interfere with daily activities;
  • 2 points for sweating that is tolerable but sometimes interferes with daily activities;
  • 3 points for sweating that is barely tolerable and often interferes with daily activities;
  • 4 points for intolerable sweating that always interferes with daily activities.

A score of 2 is considered mild, whereas a score of 3 or 4 is considered severe 14).

For craniofacial hyperhidrosis, topical 2% glycopyrrolate (compounded by a pharmacy) may be considered first-line treatment. It has shown a 96% success rate (as measured by gravimetric chemical analysis and non-Hyperhidrosis Disease Severity Scale quality-of-life surveys) with minimal adverse effects (mild skin irritation), and can be applied once every two to three days 15).

For palmar and plantar hyperhidrosis, iontophoresis may be effective as first- or second-line treatment 16). Iontophoresis is the passing of an ionized substance, usually water, through the skin by the application of a direct electrical current. Its mechanism of action is unknown 17). Tap water is poured into the device tray, and then the hands or feet are submerged while a direct electrical current is applied for a specified time, depending on the current. There are three devices registered with the U.S. Food and Drug Administration: RA Fischer MD-1a, RA Fischer MD-2, and Drionic. The procedure can be easily performed at home, and adverse effects (e.g., erythema, vesiculation, tingling) are typically mild and do not require cessation of the treatments 18). The procedure is performed three days per week until the desired effect is achieved, followed by a maintenance regimen of once per week. If tap water alone is not effective, adding a tablespoon of baking soda or one or two crushed tablets of the anticholinergic glycopyrrolate (Robinul) to each pan may be beneficial 19). A detailed description of a recommended application of iontophoresis is available in the literature 20).

Botulinum toxin injection is the most studied hyperhidrosis treatment and demonstrates consistent improvement in Hyperhidrosis Disease Severity Scale scores and in sweat production as measured in the axillae and palms 21). It may be considered first- or second-line therapy for hyperhidrosis affecting the axillae, palms, soles, or face 22). Botulinum toxins bind synaptic proteins, blocking the release of acetylcholine from the cholinergic neurons that innervate the eccrine sweat glands 23). There are several commercially available botulinum toxin preparations approved by t he U.S. Food and Drug Administration that are available to physicians who are trained in this procedure. The most commonly used is onabotulinumtoxinA (Botox) 24).

OnabotulinumtoxinA is administered intradermally in the affected area. It is packaged as a 100-unit vial that is commonly divided into 50 units total for each side. The toxin is injected intradermally in 0.1 mL aliquots per cm² 25). It is important to determine the precise area to treat using the Minor starch-iodine test 26). For this test, a 3% to 5% iodine solution is first applied to the area to be treated and allowed to dry, and then starch is applied. The sweat turns purple when in contact with the iodine and starch, precisely identifying the areas to inject 27). In most cases, treatment results last six to nine months 28). Adverse effects typically include injection-site pain and bruising, decreased grip strength when injected into the palms 29) and frontalis muscle weakness when used on the forehead 30).

Canadian guidelines recommend oral anticholinergics for treating primary hyperhidrosis with an Hyperhidrosis Disease Severity Scale score of 3 or 4 that does not resolve with topical aluminum chloride, onabotulinumtoxinA, or iontophoresis 31). The most commonly used oral anticholinergic medications are oxybutynin and glycopyrrolate 32). One study showed that oxybutynin, 2.5 to 10 mg per day, decreased excessive sweating and improved Hyperhidrosis Disease Severity Scale and non-Hyperhidrosis Disease Severity Scale quality-of-life scores (median = 76% of patients; range = 57% to 100%); however, 75% also experienced dry mouth 33). Although dry mouth is the most common adverse effect, patients may also experience abdominal symptoms, constipation, urinary retention, tachycardia, drowsiness, and blurred vision. On average, 10% of patients stop taking oxybutynin because of adverse effects 34). There is no evidence to quantify the benefit of glycopyrrolate; however, it also has a high prevalence (38%) of dry mouth 35).

A newer, noninvasive local treatment of axillary hyperhidrosis uses microwave technology 36). The application of microwave energy destroys eccrine sweat glands by creating local heat, resulting in cellular thermolysis 37). This outpatient procedure is applied with a handheld transducer after mapping the axillae using the Minor starch-iodine test. Local anesthesia is required 38). This treatment results in a decrease in the Hyperhidrosis Disease Severity Scale score of at least one point in 94% of patients and at least two points in 55% of patients 39).

Another emerging treatment in axillary hyperhidrosis is fractionated microneedle radiofrequency 40). During this procedure, microneedles are placed 2 to 3 mm under the skin, and radiofrequency energy is applied. This therapy results in a decrease in the Hyperhidrosis Disease Severity Scale score of at least one point in nearly 80% of patients 41).

Local surgical therapy has been used to treat axillary hyperhidrosis. Techniques include radical surgical excision (rarely used because of high complication and recurrence rates), limited skin excision, liposuction, curettage, and liposuctioncurettage 42). Although these techniques can initially reduce measured axillary sweating, they have high relapse rates several months after the procedure 43).

Because hyperhidrosis is thought to be secondary to excessive sympathetic stimulation, endoscopic thoracic sympathectomy has been used to treat severe cases of hyperhidrosis 44). This procedure, which has evolved from an open procedure to an endoscopic one, involves cutting or clipping sympathetic nerves 45). Referral for endoscopic thoracic sympathectomy may be indicated when less invasive therapies are ineffective 46). Although the procedure decreases or eliminates sweating in the original problem area, a common late complication is compensatory sweating in other areas, usually in the abdomen, back, gluteal region, and legs 47).

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 the 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 localized 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 anesthetic.

  • Tumescent liposuction (sucking them out)
  • Subcutaneous curettage (scraping them out)
  • Microwave thermolysis (the MiraDry® system approved by FDA in 2011)
  • Subdermal Neodymium 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 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.

Generalized hyperhidrosis prognosis

The outlook for secondary localized or generalized hyperhidrosis depends on the cause.

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