Hyperhidrosis

Introduction One of the oldest described dermatologic conditions, primary hyperhidrosis is an embarrassing disorder that, even today, is misconceived as rare and untreatable. Hyperhidrosis is a disorder characterized as perspiration in excess of the bodys physiologic need and can significantly impact ones occupational, physical, emotional, and social life.

Hyperhidrosis is delineated into two classifications of either primary or secondary hyperhidrosis. Primary hyperhidrosis is distinguished as a chronic, idiopathic disorder of excessive perspiration in a bilateral, symmetrical manner. Primary hyperhidrosis has been associated with hyperactivity of the sympathetic nervous system and can affect the palms, soles, axillae, face, and scalp as well as other areas.

Secondary hyperhidrosis is due to an underlying condition, such as an infection, endocrine disorders, metabolic disorders, neoplastic diseases, neurologic conditions, spinal cord injuries, cardio-vascular disorders, respiratory disorders, anxiety, and stress. Epidemiology Primary focal hyperhidrosis has an average age of onset of 25 years.

It would appear that hyperhidrosis is a disease of childhood which may peak in early adulthood. A large epidemiologic survey revealed that approximately 70% of people did not consult a physician for this presentation.

Primary hyperhidrosis is a relatively common disorder, affecting nearly 3% of the population, with the highest prevalence rates among those aged 18 to 54 years. A genetic component has been suggested to contribute to primary hyperhidrosis as family history has been positive in 30% to 65% of patients.

Pathophysiology Hyperhidrosis is a disease of the eccrine sweat glands. The human body has up to 4 million sweat glands, of which approximately 3 million are eccrine sweat glands. The remainder are apocrine glands which are not involved in hyperhidrosis. Hyperhidrosis appears to be due to excessive sympathetic activity as there are no histopathologic changes of the eccrine glands. Thermoregulatory sweating is the major mechanism of heat dissipation by whole-body eccrine glands, is controlled by the preoptic area of the hypothalamus, and is diurnal or nocturnal.

Emotional sweating, always diurnal, is controlled by the anterior cingulate cortex, and its distribution is limited usually to the face, axillas, palms, and soles. Both higher centers descend to synapse on the intermediolateral cell column neurons of the spinal cord. From there, myelinated preganglionic sympathetic nerves exit the cord via the ventral roots and enter the segmental paravertebral sympathetic ganglia or course up and down the sympathetic chain and enter paraverterbral ganglia at other levels. Unmyelinated postganglionic sympathetic fibers exit the ganglion and rejoin the segmental spinal nerve or plexus, eventually innervating hair follicles, sweat glands, and vascular effectors of the skeletal muscle and skin of the trunk and limbs. The nerves release acetylcholine onto the muscarinic cholinergic receptors of the sweat glands.

Primary Focal (Essential) Hyperhidrosis Primary Focal (Essential) Hyperhidrosis is one of the most common disorders of eccrine sweating. Primary focal hyperhidrosis is characterized by excessive sweating of small regions of the skin, such as the axilla, palms, soles, or face. The onset is usually in adolescence (usually under 25 years of age), although it can begin early in childhood, especially the palmar-plantar variants. The disease manifests as bilateral and relatively symmetric sweating, often with cessation during sleep. Sweating may be phasic or continuous; when continuous; sweating is most troublesome in summer.

Phasic outbursts with minor emotional activity are similar year round.

Palmo Plantar hyperhidrosis The sweating of the palms and soles may be either continuous or phasic. When continuous it is worse in the summer, and not so clearly precipitated by mental factors. When phasic, it is usually precipitated by minor emotional or mental activity, and is not markedly different in summer and winter. The hands may be cold, and show a tendency to acrocyanosis. Hyperhidrosis may be associated with Raynauds phenomenon and reflex sympathetic dystrophy , or may follow cold injury. Apart from the embarrassing nature of the disorder, complications include pompholyx and contact dermatitis. Control of plantar hyperhidrosis may reduce the exacerbations of contact dermatitis to footwear constituents. The condition of pitted keratolysis of the feet, due to infection with Micrococcus sedentarius , is associated with hyperhidrosis. Axillary sweating may be continuous, or more commonly phasic, and may or may not be aggravated by heat or mental activity. It is uncommon before puberty. Axillary sweating on undressing is very common. Axillary hyperhidrosis is due to overactivity of eccrine glands, unlike axillary odour which is mainly apocrine in origin. Craniofacial hyperhidrosis is often phasic, occurs in middle age and may be exacerbated by heat, exercise and eating, but, unlike true gustatory hyperhidrosis, not exclusively so. It may be more persistent and presents at a later age than palmoplantar

hyperhidrosis. Sweating sufficient to soak the hair is an additional embarrassment. Cold-induced sweating syndrome. This is a rare, familial condition in which profuse sweating of the trunk occurs when the skin is cooled to between 7 and 10C [7]. There are associated physical anomalies including a high arched palate, inability to fully extend the elbows and scoliosis. Chromosomal anomalies have recently been identified.

Gustatory hyperhidrosis Sweating on the lips, forehead and nose after eating certain foods occurs physiologically in many people. Hot spicy foods are the most likely cause. The central connections of this reflex are not fully known. Gustatory hyperhidrosis also occurs in pathological conditions involving the autonomic nervous system. Localized areas of intense hyperhidrosis may occur on the face, and even on the knees. These disorders are very rare, usually start in childhood and are not progressive. The commonest cause is damage to the sympathetic nerves around the head and neck. The commonest site is within the distribution of the auriculotemporal nerve, following injury, abscess or operation in the parotid region (auriculotemporal or von Freys syndrome). Submental gustatory sweating follows injuries involving the chorda tympani, and sweating in the distribution of the greater auricular nerve commonly follows radical neck surgery.

Gustatory sweating may occur in diabetes as part of a wide-spread autonomic neuropathy. It has also followed herpes zoster.

Classification Of

Hyperhidrosis Primary Hyperhidrosis

Secondary Hyperhidrosis

Measuring hyperhidrosis The Minor starch iodine test is a simple way to detect the presence of sweat. After the area to be studied is dried thoroughly, iodine solution is painted over the affected area, and a starch powder such as corn starch is applied. With the interaction of sweat, the area turns a purple black color. For iodine-sensitive patients, Alizarin or Ponceau red dye and starch can be used. The pink powder turns to a bright red color when wet. The Ninhydrin sweat test is another variant that can be used. Gravimetric assessment identifies the amount of sweat produced during a given time. The technique involves applying pre-weighed filter paper to the affected area (typically 5 min) and then measuring the production of sweat by reweighing the filter paper. Evaporation must be prevented from occurring. Hund suggests a minimum of 100 mg/5 min for men and 50 mg/5 min for women to identify axillary hyperhidrosis. A third method used to measure disease severity is the use of quality of life scales and questionnaires. Several tools are available, but two of the more commonly used scales are the DLQI and the HyperHidrosis Impact Questionnaire (HHIQ), which help to quantify the impact, burden and disease severity.

A newer tool, the hyperhidrosis disease severity scale (HDSS) is based on one question that the patient can answer in the office.

Treatment Many treatments are available for hyperhidrosis, but none are effective in everyone. Therapy should be tailored to the needs of the individual based on factors such as age and health status of the patient, location of disease, occupation and lifestyle. Treatment of hyperhidrosis can be divided into topical, oral, surgical, and nonsurgical treatments (botulinum toxin). These therapeutic options differ with respect to their efficacy, duration of action, side effects, and cost of treatment. Topical treatments. Topical treatments are limited to antiperspirants containing aluminum chloride in concentrations ranging from 20% to 25%. The mechanism of action involves mechanical obstruction of the eccrine gland duct. The major limitation of aluminum chloride is localized burn-ing, stinging, and irritation. The main indication for these products is as a first-line treatment for mild axillary hyperhidrosis.

Atropine-like drugs may be absorbed sufficiently to produce a beneficial local effect without associated systemic side effects, but none of those at present available can be relied upon to do so. Poldine methosulphate, 14% in alcohol, suppresses experimentally induced sweating, but unfortunately is less valuable on the palms, soles and axillae. Topical 0.5% glycopyrronium bromide cream has been successfully used in gustatory hyperhidrosis in diabetics and 2% aqueous solution has been used in scalp hyperhidrosis. Eccrine duct blocking agents. These drugs act by impeding the delivery of sweat to the skin surface. Formalin 1% soaks have long been used for treatment of hyperhidrosis of the feet, but are unsuit-able for the hands and axillae. Glutaraldehyde 10% in a buffered solution, pH 7.5, swabbed onto the feet three times weekly, has helped some patients. Systemic treatments Oral anti-cholinergic agents such as glycopyrrolate or amitriptyline represent the main systemic medications for hyperhidrosis. They inhibit synaptic acetylcholine and therefore interfere with neuroglandular signaling. Atropine-like drugs have been used to block the effect of acetylcholine on the sweat glands, but their side effects are often more troublesome than the hyperhidrosis itself. These include dryness of the mouth, constipation, urinary retention and disturbances of vision, due to paralysis of accommodation, but more serious side

effects, for example glaucoma, hyperthermia and convulsions, can occur. The oral antimuscarinic agent oxybutinin, usually used to treat bladder instability, has been reported to be effective for generalized hyperhidrosis in a small series of case. Calcium-channel blockers, such as diltiazem, have helped some cases. In cases with a pronounced emotional factor, sedative or tranquillizing drugs are often useful, but psychiatric treatment may be necessary. Iontophoresis. Iontophoresis involves the passage of ions by means of an electrical current into the skin. This electrical charge appears to occlude the eccrine duct and interferes with eccrine gland secretion. One of the more satisfactory methods of control-ling hyperhidrosis of the hands and feet is by iontophoresis, either using tap water or anticholinergic drugs such as glycopyrronium bromide. The main indication for iontophoresis is in palmar or plantar hyperhidrosis, where the efficacy ranges from 80% to 90%. Direct current is usually used, with each palm or sole being treated for 30 min with 20 mA, initially three times a week. Once euhidrosis is established, monthly maintenance treatment may be sufficient. Alternating current is less effective, but may usefully be combined with direct current (alternating current offset) to produce a safer, more comfortable treatment. The main limitation of this therapeutic modality is that it is time consuming (requires 30 to 40 minutes per treatment site daily for at least 4 days of the week) and may cause skin irritation, dryness, or peeling.

Sweating is well controlled after 6 to 10 treatments; however, long-term maintenance therapy is generally required at 1 to 4 week intervals. Iontophoresis is considered a second-line treatment for palmar or plantar hyperhidrosis, following aluminum chloride antiperspirants. Surgical treatments. Surgical treatment primarily involves thoracoscopic sympathectomy with success rates in the range of 80% to 90% for primary focal hyperhidrosis of the axilla, palms, soles, and face. A major limitation of this surgical procedure is compensatory hyperhidrosis with an incidence of 80%. Other surgical complications include pneumothorax and hemothorax. Although this procedure has a high efficacy rate, the associated risk of complications necessitates proper patient selection (generally those with severe hyperhidrosis who are unresponsive to other treatments) and detailed informed consent to avoid unnecessary frustration following treatment. Other surgical procedures with reported efficacy in axillary hyperhidrosis include liposuction and subcutaneous curettage.

Botulinum toxin A (Botox). Botulinum toxin is produced by Clostridium botulinum and acts by inhibiting acetylcholine release at the neuromuscular junction.

Previously used as an off-label treatment for hyperhidrosis, the US Food and Drug Administration approved the use of botulinum toxin type A (BT-A) for axillary hyperhidrosis in July 2004. Odorless, tasteless, and colorless, botulinum is the most poisonous substance known. Botulinum toxin type A is 1 of 7 types (A-G) of botulinic toxins from the gram-positive bacillus Clostridium botulinum. Botulinum toxin has a reported efficacy of greater than 90% for primary focal hyperhidrosis of the axilla, palms, and soles. This treatment method is extremely safe. Transient intrinsic muscle weakness is reported in less than 1% of patients treated for palmar hyperhidrosis. The major contraindications include neuromuscular disorders such as myasthenia gravis, pregnancy and lactation, organic causes of hyperhidrosis, and medications that may interfere with neuromuscular transmission. The cost of the drug and need for repeated treatments appear to be a notable limitation to this modality. Botulinum toxin for axillary hyperhidrosis is a safe, well tolerated, and highly efficacious treatment modality. Dosages range from 50 to 100 units per axilla. The usual starting dose is 50 units per axilla. A starch iodine test is often used and results in purple to black discoloration which delineates the affected area of excessive sweating. Pain associated with these intradermal injections is minimal; however, a topical anesthetic can be used to further minimize the discomfort. The mean duration of effect is 6 to 7 months. Botulinum toxin for palmar or plantar hyperhidrosis is also reported to be safe and effective; however, the main limitation of this indication is the fact that most patients find the injections in

the palms and soles quite painful. Therefore, a regional nerve block is required prior to the botulinum toxin injections. The duration of efficacy for palmar and plantar hyperhidrosis treated with botulinum toxin is in the range of 4 to 6 months.

International Hyperhidrosis Society

http://www.sweathelp.org

REFERENCES BOOKS
1. Fitzpatrick's Dermatology in General Medicine, 7e CHAPTER 82 (pg720 pg726) 2. Rook's Textbook of Dermatology, 8e CHAPTER 44 3.

Clinical Uses of Botulinum Toxins, CHAPTER 9

ARTICLES

4. An Epidemiological Study of Hyperhidrosis 2007 American Society for Dermatologic Surgery

5.

A Comprehensive Approach to the Recognition, Diagnosis, and Severity-Based Treatment of Focal Hyperhidrosis: Recommendations of the Canadian Hyperhidrosis Advisory Committee 2007 American Society for Dermatologic Surgery

6. Hyperhidrosis: An Approach to Diagnosis And Management Dermatology Nursing Dec 2004 7. Hyperhidrosis: Evolving Therapies for a WellEstablished Phenomenon Mayo Clin Proc. 2005;80(5):657-666