Hyperhidrosis overview

# Overview
Primary hyperhidrosis is the condition characterized by abnormally increased perspiration, in excess of that required for regulation of body temperature.  There is controversy regarding the definition of hyperhidrosis, because any sweat that drips off of the body is in excess of that required for thermoregulation. Almost all people will drip sweat off of the body during heavy exercise.

# Historical Perspective
- In 2006, gene mutations were first identified in the pathogenesis of focal hyperhidrosis. 
- In 1950, medical therapy using antimuscarinic agents was developed by Grimson, et al to treat hyperhidrosis.

# Classification
- Primary hyperhidrosis must be distinguished from secondary hyperhidrosis, which can start at any point in life.  For some, it can seem to come on unexpectedly. The latter form may be due to a disorder of the thyroid or pituitary gland, diabetes mellitus, tumors, gout, menopause, certain drugs, or mercury poisoning. Such secondary forms may have more serious consequences than just hyperhidrosis, making medical consultation advisable.
- Hyperhidrosis can also be classified as focal or generalised.
- Focal hyperhidrosis is most commonly seen during emotional outbursts like sweating of palms, axillae, face etc. Generalised hyperhidrosis affects the entire body and can be triggered by emotion or exertion/heat for thermoregulation.

# Pathophysiology
- Primary hyperhidrosis affects about 0.6-0.1% of the general population.
- Onset of symptoms occurs during puberty, seen as excess sweating of face, palms, soles and axillae, and symptoms usually resolve with age. 

## Physiology
- Sweat is a hypotonic solution produced by eccrine glands and apocrine glands which are distributed all over the body.
- Most of the body's sweat is produced by the eccrine glands. Eccrine glands have the highest concentration in the axillae. These glands play an important role in thermoregulation. 
- Apocrine sweat glands are seen in the axillae and urogenital region. 
- Sweating is caused by two broad impulses- thermoregulation and emotion. The thermoregulatory centre of sweating is located in the hypothalamus and is triggered by increased body temperature (eg., fever) and the emotion centre of sweating is located in the limbic system and is triggered by extreme emotional states like anxiety, fear etc.

## Pathology
- It is not known what causes primary hyperhidrosis. One theory is that hyperhidrosis results from an overactive sympathetic nervous system, but this hyperactivity may in turn be caused by abnormal brain function. 
- Some patients afflicted with the condition experience a certain degree of reduction in their quality of life, depending on how severe their condition is.  
- Sufferers feel at a loss of control because perspiration takes place independent of temperature and emotional state. However, anxiety can exacerbate the situation for many sufferers.  A common complaint of patients is that they get nervous because they sweat, then sweat more because they are nervous.
- Other factors can play a role; certain foods & drinks, nicotine, caffeine, and smells can trigger a response (see also diaphoresis).
- Primary focal hyperhidrosis is the most common type and is seen during puberty in the axillae and face. 
- Secondary focal hyperhidrosis is a disorder of defective thermoregulation and is seen in neuropathy affecting peripheral nerves like diabetic neuropathy, spinal cord disease etc.
- Generalised primary and secondary hyperhidrosis involve the whole body. Secondary general hyperhidrosis is seen in disorders of thermoregulation like fever, hyperthyroidism etc. 
- Some forms of primary hyperhidrosis are genetically transmitted in either autosomal dominant or recessive pattern.

# Causes
- The cause of primary hyperhidrosis is unknown, although some surgeons claim it is caused by sympathetic over-activity.
- Nervousness  or excitement can exacerbate the situation for many sufferers.
- Other factors can play a role; certain foods and drinks, nicotine, caffeine, withdrawal from alcohol, and smells can trigger a response.
- One form of congenital hyperhidrosis is seen in Riley-Day syndrome, seen among Ashkenazi Jews. Affected children have hyperhidrosis, decreased pain sensitivity, areflexia.
- A common complaint of patients is they get nervous because they sweat, then sweat more because they are nervous. 

# Clinical features
- Excess sweating involving face, axillae, palms and soles
- Sweating usually causes social embarrassment and impairs social activities. 

# Differential diagnosis
- Diabetic hypoglycaemia
- Thyrotoxicosis
- Hyperpyrexia
- Pheochromocytoma
- Hot flushes in menopause 
- Cholinergic medication
- Tricyclic antidepressant use
- Eccrine angiomatous hamartoma 
- Frey syndrome

# Epidemiology and demographics
- The prevalence of hyperhidrosis is around 3% of the general population. 
- It affects men and women equally.
- There is no racial predilection for hyperhidrosis.

# Risk factors
- There are no known risk factors for hyperhidrosis.

# Natural History, Complications and Prognosis
- Most cases of focal hyperhidrosis are seen during puberty in teenagers.
- Early clinical manifestations include facial and axillary sweating.
- Common complications of hyperhidrosis include athlete's foot and pitted keratolysis.
- Prognosis is generally good with medical, topical or surgical therapy, but patients generally suffer from embarrassment, anxiety or depression due to their condition.

# Diagnosis

## Diagnostic criteria
The diagnosis of hyperhidrosis is made when the following diagnostic criteria are met. 
- Sweating involving face, axillae, palms and soles for 6 months or longer.
- No episodes of nocturnal sweating.
- Episodes of excess sweating which occur at least once per week.
- Sweating is symmetrical and bilateral.
- Onset of symptoms at age<25 years.
- Sweating impairs activities of daily life.
- Positive family history of hyperhidrosis.

## History and Symptoms
- Hyperhidrosis can either be generalized or localized to specific parts of the body.
- Hands, feet, axillae, and the groin area are among the most active regions of perspiration due to the relatively high concentration of sweat glands; however, any part of the body may be affected.
- Patients often feel embarrassed in social situations because situations like shaking hands is difficult for people with sweaty palms.
- Patients also reports a degree of disability in writing or holding objects.

## Laboratory Findings
The following are diagnostic tools used to diagnose hyperhidrosis.
- Iodine starch test is the most common initial diagnostic tool used to diagnose hyperhidrosis. To perform the test, iodine is applied to the affected skin and starch powder is applied over it. If there is sweat on the skin, the starch and iodine react and a violet colour is seen. This test is helpful to identify focal hyperhidrosis. 
- The amount of sweat can be quantified by using quantitative sudometry. This test stimulates sweat production with acetylcholine electrophoresis. The sweat produced is detected by passing dehumidified nitrogen gas over the required area of skin enclosed in a chamber. The humidity and perspiration is then plotted on a chart and compared.
- Gravimetry is another method to diagnose hyperhidrosis. Filter paper is applied over affected areas (palms, soles, axillae) and after a defined period of time weight of filter paper before and after is measured. Hyperhidrosis is diagnosed as axillary sweating of >136 mg/min/m2, palmar sweating sweating of >50 mg/min/m2.

## Imaging Findings
- There are no imaging findings associated with hyperhidrosis.

# Treatment
- Hyperhidrosis can usually be very effectively controlled, but there is no known permanent cure because little is known about the cause behind excessive sweating.
- Treatment for hyperhidrosis consists of local therapies, surgical options and pharmacological therapy.

## Medical Therapy
Local therapy options
- Over the counter antiperspirants containing aluminium chloride. 
- Botulinum injections. Botulinum toxin type A has been shown to be effective in treating plantar hyperhidrosis. 
- Microwave ablation has been shown to have longer lasting antiperspirant effect in axillary focal hyperhidrosis. 
- Tap water iontophersis is used for palmar and plantar hyperhidrosis.
- Gustatory hyperhidrosis is treated with glycopyrrolate.
Pharmacological therapy options
- Anticholinergic drugs like oxybutynin.
- Tricyclic antidepressants have been used in treating spontaneous gustatory and facial sweating. Although several cases of hyperhidrosis have been reported as a side effect to TCA use.
- Calcium channel blockers

## Surgical therapy
- Liposuction curettage for axillary hyperhidrosis.
- Thoracic sympathectomy for axillary and palmar hyperhidrosis.

# Prevention
- There are no primary preventive measures for hyperhidrosis.