Hyperhidrosis: Diagnosis and New Treatments

H yperhidrosis, the overproduction of sweat by the exocrine sweat glands, can be a psychological and socially debilitating disorder by restricting the personal as well as professional lives of those who suffer from it. Two forms of hyperhidrosis exist: localized (axillary or palmar/plantar) or generalized, affecting the entire skin. Also, the condition may predispose those individuals to other dermatoses such as fungal and bacterial infections. We must recognize the importance of treating hyperhidrosis, and not ignore the seriousness of this condition.1,2 Sweating allows us to regulate our body temperature and prevent overheating. There are two types of sweat glands in the human body: exocrine and apocrine glands. Exocrine glands, found all over the skin, are densely grouped in the palmar/ plantar and axillary regions of the skin. These glands produce an aqueous secretion of electrolytes. Apocrine glands, commonly located in the anogenital and axillary regions, secrete a lipid-rich secretion. This fluid, which is slightly viscous, acts as a pheromone. Apocrine glands don’t control thermoregulation.1,2,3 The Science of Sweat Sweat glands are innervated by sympathetic postganglionic fibers of nerves using acetylcholine as their neurotransmitter. Sweat control centers in the hypothalamus contain neurons that respond to changes in temperature and cerebrocortical events. Patients with hyperhidrosis have morphologically normal sweat glands, but they have an abnormal neurologic response to hypothalamic stimuli. The hypothalamic sweat centers of these patients are more sensitive to emotional stimuli. Excessive sweating of the hands and feet leads to a cycle in which the lowered skin temperature caused by evaporative cooling increase the reflexive sympathetic outflow, thus aggravating the hyperhidrosis.2,3 Generalized hyperhidrosis may be due to exposure to heat, humidity, certain foods, alcohol and/or exercise. It also may be a sign of more serious, internal disease — febrile illness, infection and malignancy can all cause hyperhidrosis. In addition to shock, syncope and pain, metabolic diseases such as hyperthyroidism, diabetes mellitus, reactive hypoglycemia, gout, hyperpituitarism and pheochromcytoma can cause generalized hyperhidrosis. Many neurologic (familial dysautonomia) and vascular diseases can also cause hyperhidrosis. Also, you should always consider certain drugs as a cause of hyperhidrosis. These include: propanolol, physostigmine, pilocarpine, tricyclic antidepressants, selective serotonin reuptake inhibitors and mercury.2,3 Localized hyperhidrosis may be the result of heat exposure, but it also may be secondary to neurologic lesions such as spinal cord trauma, peripheral neuropathy, brain neoplasms and Parkinson’s disease. Certain dermatologic syndromes such as nail-patella syndrome, keratosis palmaris and plantaris and Unna-Thost keratoderma can be associated with hyperhidrosis. Here, we’ll focus on the diagnosis and treatment of localized hyperhidrosis.2,3 Evaluating the Patient When evaluating a patient with localized hyperhidrosis, you should know that only a small portion of the affected area has overactive sweat glands. Use the starch iodine test, a simple, useful diagnostic tool, to help make the hyperhidrotic area of skin more apparent. Apply a 2% iodine solution to the affected area and let it dry. Next, apply a starch powder to the dried iodine solution. The hyperhidrotic skin turns a deep blue-black color.1 Treatment options for hyperhidrosis may be pharmacologic or nonpharmacologic. Pharmacologic treatments may be topical or systemic. Non-pharmacologic treatments include physical modalities or surgery. Pharmacologic Treatments Topical Therapy. The most common first-line therapy for hyperhidrosis is aluminum chloride. It’s thought to work by causing mechanical obstruction of the exocrine sweat gland pores, resulting in atrophy of the gland. Have patients apply it to their skin at night, when the exocrine sweat glands are largely inactive because this will enable better penetration in the skin. You may occasionally recommend occlusion with plastic wrap to further enhance penetration of the active ingredient. Concentrations of aluminum chloride preparations may vary from 10% to 15% for the axillary regions, and to 30% for thicker areas of skin such as the hands and feet. Patients should apply the solution every night for 1 week, and then once every 1 to 2 weeks for maintenance. Success rates of 90% have been reported for the treatment of axillary hyperhidrosis. Although allergic contact dermatitis has not been readily described, irritant contact dermatitis may occur quite often, with symptoms of burning and stinging. Aluminum chloride can have a damaging effect on textiles, so warn patients to wear inexpensive garments while using this treatment. Other topical therapies that may be useful include: glutaraldehyde, tannic acid or formaldehyde, which are painted on to the affected skin. One major disadvantage of these agents is the risk of sensitization leading to allergic contact dermatitis.1,2,3 Systemic Therapy. Systemic agents used for hyperhidrosis include benzodiazepines, systemic anticholinergics, NSAIDs, calcium channel blockers, clonidine and propoxyphene. Most of these are useful in treating hyperhidrosis induced by other systemic medications. For example, clonidine is used to treat hyperhidrosis induced by tricyclic antidepressants. Benztropine (an anticholinergic) is used to treat hyperhidrosis induced by selective serotonin reuptake inhibitors.2,3 Nonpharmacological Treatments Physical Therapy. Iontophoresis has been effective in controlling hyperhidrosis. It involves a complex process of ion transport through the skin using galvanic current. Although the full mechanism of action is unclear, it’s thought that a disruption of the ion channel occurs in the secretory glomeri of the sweat glands.8 The procedure involves placing the hands or feet into water filled basins and conducting a direct current of electricity into the water. Low-level currents are used, and the sensations felt by the patient are not considered painful. Treatment sessions last 10 to 20 minutes and are administered three to four times per week. The response rate for palmoplantar disease has been reported at 90%. It takes five to 10 sessions to notice an improvement, and 10 to 15 sessions to reach a successful therapeutic outcome. Maintenance treatments are given once or twice per week. By adding anticholinergic drugs such as glycopyrronium bromide to the tap water, the effects of iontophoresis last longer and appear sooner. Systemic effects of the anticholinergic drugs, such as dry mouth and urinary retention may be observed, making regular tap water iontophoresis a more preferable option.1,3 Surgical Options Surgical excision of the sweat glands with extensive undermining is an invasive procedure with relapse rates of up to 10% to 20%. Unsightly scar formation can be disfiguring and usually requires complex closure methods in order to avoid cicatricial contracture. In some cases physical impairment can ensue.4 Tumescent liposuction (for axillary hyperhidrosis) is an option, and is often accompanied by curettage with a scraper on the underside of the overlying dermis. Small incisions are made and there are generally few complications apart from hematoma, post-operative pain and paresthesia. Liposuction appears to be a safe and effective treatment option for axillary hyperhidrosis.5 Sympathectomy is a surgical procedure that involves removal of the sympathetic nerve trunks. To denervate the sweat glands of the hands, the T2 toT3 sympathetic nerve trunk is removed. For the feet, the L3 ganglia are removed. For the axillary region, the T3 toT6 ganglia must be removed. Severe complications such as Horner’s syndrome, pneumothorax, hemothorax and infection have often followed removal of these thoracic sympathetic ganglia. More recently, less invasive surgical approaches with the use of endoscopy have allowed this procedure to be used with increased safety and fewer complications. However, complications such as gustatory sweating and compensatory hyperhidrosis have occurred in more than one-third of these patients.6,7 Therapeutic Advances Botox, or botulinum toxin type A, is one of the most exciting therapeutic advances in the treatment of hyperhidrosis. Botulinum toxin type A is a neurotoxin, which irreversibly inhibits the release of acetylcholine from presynaptic nerve endings near the neuromuscular junctions and exocrine glands. In Europe two forms of botulinum toxin A exist: Botox and Dysport (1 U of Botox is equivalent to 3 to 5 U of Dysport). To use this therapy, first use the starch–iodine test to visualize the hyperhidrotic area. Then, inject the toxin in small intracutaneous injections, or move the needle under the skin to spread the toxin throughout the desired area. Early reports described using 50 U of Botox or 200 U of Dysport to achieve 3 to 7 months of remission of the hyperhidrosis.3,8 More recently, a study in the April 2002 Journal of the American Academy of Dermatology reported using a high- dose Botox treatment of up to 200 U per axilla. In an open study, 47 patients with axillary hyperhidrosis were treated with intracutaneous injections of Botox. A total dose of 200 U of Botox was used per axilla, and patients were followed for 29 months. Within 6 days of the injection, all patients reported cessation of excessive sweating. Each axilla was injected 3 to 5 days apart. Results were promising in that the higher doses were able to prolong the anhidrotic effect for more than 19 months. No systemic side effects were observed. Additionally, only four relapses occurred after 12 months (less than 12%), showing that the higher doses reduced the overall number of relapses. More importantly, long-term remissions of up to 29 months were induced.9 Treating Palmar Hyperhidrosis Botulinum toxin has also been used to treat palmar hyperhidrosis. You need doses of 100 U to 165 U of Botox for efficacy, and injections should be repeated at 9- to 12-month intervals. Nerve blocks are needed for treatment of palmar hyperhidrosis, due to the large number of injections needed per palm. Temporary muscle weakness of the hand lasting up to 8 weeks has been described. Although the safety and efficacy profile of botulinum toxin type A makes this an attractive treatment option for axillary and palmar hyperhidrosis, the high cost of the product is a limiting factor for many patients.1,10 Other Choices There are also some more natural approaches. Herbal remedies, such as sage tea and sage tablets, have been reported to improve the signs and symptoms of localized and generalized hyperhidrosis. The mechanism of action is unclear, and only a few anecdotes have described the efficacy of these products. Others have tried psychosomatic therapies, such as relaxation exercises and meditation. No firm data exist on the efficacy of these treatments.1 Many Options For a once difficult-to-treat condition, hyperhidrosis can now be managed by a variety of methods. In addition to treatments such as aluminum chloride, iontophoresis and systemic anticholinergics, newer options such as liposuction and Botox may offer promising results. Invasive procedures such as sympathectomy and surgical excision may be necessary in severe cases but only after other treatments have failed.