Hyperhidrosis is a pathological condition of overperspiration due to excessive secretion by the eccrine sweat glands in amounts greater than required for physiological needs. The disorder often leads to personal embarrassment and professional difficulties in the workplace. It is estimated that Americans alone spend in excess of $500 million annually on products designed to decrease sweating. Patients will often seek medical attention but the enormity of the problem is often disregarded by the medical professional, resulting in despair and isolation for those who suffer from hyperhidrosis. It behooves all treating physicians to acquire the knowledge necessary to diagnose and treat the various causes of hyperhidrosis appropriately. Primary hyperhidrosis, also known as idiopathic, localized or essential hyperhidrosis, is a disorder of sweating characterized by an exaggerated response of both the eccrine and aprocrine sweat glands to a normal stimulus, which is usually an emotional stimulus. The disorder predominantly affects the palms, soles and axillae, and is not associated with any underlying systemic disease. The symptoms usually present early in life, generally before the age of 20. Unfortunately, there is no known cause for primary hyperhidrosis, making it difficult to eradicate. The most focal form of hyperhidrosis is palmoplantar hyperhidrosis, which affects only the palms of the hand and the sole of the foot. Secondary hyperhidrosis occurs in association with a systemic disease or underlying condition, and results in generalized hyperhidrosis that usually responds to the removal or control of the causative agent. Conditions that may lead to secondary hyperhidrosis include metabolic diseases such as thyrotoxicosis, diabetes mellitus, hypoglycemia, pheochromocytoma, hyperpituitarism; medications such as propanolol, tricyclic antidepressants, serotonin reuptake inhibitor antidepressants; and neurological conditions such as Riley-Day syndrome, autonomic dysreflexia and hypothalamic lesions. The onset of secondary generalized hyperhidrosis is usually in adulthood when the disease process occurs or the medication is prescribed. The examining physician must differentiate the type of hyperhidrosis present and search for any underlying causes before presuming primary hyperhidrosis. Recognizing The Clinical Signs And Symptoms Of Primary Hyperhidrosis Patients suffering from primary hyperhidrosis usually complain of excessive moisture on the socks or within the shoes; moisture or damage to their clothing due to chemicals combined with the sweat; and offensive odor. The increased moisture on the skin results in an increased incidence of contact dermatitis, blistering and dermatophyte, bacterial and viral infections. Disease conditions such as tinea pedis, verruca and pitted keratolysis commonly occur with hyperhidrosis. The physical examination often reveals two different hyperhidrotic foot types. The first type will present with visible moisture on the feet in small droplets in a moccasin distribution. The second type shows no visible droplets. However, the skin is very white and macerated from the moisture being absorbed and contained within the skin itself. There is a variant of the second type known as symmetrical lividity of the soles as described by Pernet in 1925. This hyperhidrotic foot presents with symmetrical soggy white hyperkeratotic plaques with sharp bluish-red margins. As the sweat is trapped in the plantar skin, this foot type is often associated with bromhidrosis (odiferous hyperhidrosis) and an increased incidence of infectious organisms. Understanding The Pathophysiology Of Hyperhidrosis There are 3 to 4 million sweat glands over the body surface, which allows for evaporation to cool the body and protect it from overheating. There are two types of sweat glands, the eccrine gland and the aprocrine gland. Eccrine glands are present all over the body but are primarily concentrated in the palms, soles and axillae. They make up the majority of the sweat glands and are responsible for the bulk of the sweat produced for thermoregulation. The sympathetic nervous system innervates the eccrine glands and stimulates activity through the release of acetylcholine. The sweat produced is an aqueous solution rich in electrolytes and is usually released in response to emotional stimuli or environmental stimuli such as high temperature, humidity or exercise. The eccrine glands on the palms and soles are the most sensitive to emotional stimuli. This becomes evident in a stressful or anxiety producing situation. The aprocrine glands are localized to the axillary and genitoanal region, and are regulated by hormonal processes as opposed to thermoregulatory processes. The secretion is viscous, rich in lipids, steroids and other hormones, and has very little homeostatic function in humans. Addressing Personal Hygiene Habits The management and treatment of primary hyperhidrosis begins with personal hygiene habits. Patients should avoid occlusive shoes and socks. Encourage them to wear leather and fabric shoes, and to use socks that wick water away from the skin. Patients should change these midday if necessary and rotate shoes to allow them to dry between use. Topical powders should contain no starch and should be used daily. Zeasorb Powder® (Stiefel Laboratories, Inc.) has been shown to absorb much more moisture than talcum and is excellent for this purpose. Avoiding hot, spicy foods that can result in gustatory hyperhidrosis and stimulants such as coffee may also be helpful. If the management described above does not decrease the degree of sweating to tolerable levels, one can render additional treatment. Individualize the treatment to the severity of sweating and the personal preferences of the patient. There are a variety of treatment options available, all with their own advantages, disadvantages, adverse side effects and complications. Common forms of treatment include topical medications, systemic medications, iontophoresis, botulinum toxin A (Botox) injections, behavioral therapy and surgery or invasive techniques. Pertinent Points On Topical Medications Applying a topical medication is the most common of all treatments and is usually the first attempt to control localized primary hyperhidrosis on the plantar foot, the palms and axillae. Aluminum chloride hexahydrate 20% in absolute ethyl alcohol is the most effective topical agent with the least number of adverse effects. It is available via prescription as Drysol or Xerac AC, and patients would apply this nightly until achieving the desired dryness. The original recommendation was to place this medication under occlusion but researchers have shown it doesn’t enhance the efficacy of the medication and may result in a greater incidence of skin irritation or dermatitis. If skin reaction does occur, one may use 1% cortisone cream to resolve it. Patients should apply aluminum chloride at night and wash it off in the morning before donning shoes and socks due to the formation of hydrochloric acid when this chemical is exposed to moisture from sweat. They should repeat this each night until sweating is within normal physiologic levels and then reapply aluminum chloride every seven to 21 days to maintain control of the hyperhidrosis. The mechanism of action is still unknown but it may obstruct the eccrine sweat gland pore or cause atrophy of the secretory cells. The aluminum chloride products provide a safe, effective means to control sweating but be aware that they do have a short duration of action and may cause a skin irritation. Other topical agents have been used with varying success. Formaldehyde has been shown to be effective but there is a significant adverse effect of allergic contact eczema and hypersensitivity. Methenamine is a condensation of formaldehyde and ammonia, which is formulated by a compound pharmacist in a 5% gel stick formula that slowly releases formaldehyde in a concentration low enough to avoid a contact allergy yet effectively control the hyperhidrosis. Patients would apply methenamine twice daily until achieving the desired response and then taper it to maintenance use. Glutaraldehyde 10% buffered solution and tannic acid (strong tea) have also been used effectively for treating primary hyperhidrosis. However, they also have major drawbacks since they stain the skin a dirty brown color and patients may experience allergic sensitization. A Review Of Other Conditions Associated With Hyperhidrosis Dyshidrosis is not a sweat gland disorder per se but has been misnamed after being associated with hyperhidrosis. It is better known as pompholyx and refers to a condition of recurrent, acute or chronic vesiculation of the hands and/or feet. Since clinicians often saw the vesicles with hyperhidrosis, it was also misnamed as a disorder of the sweat glands. It is actually an acute eczematous dermatitis that responds to topical cortisone. The hyperhidrosis is an important concomitant condition that one should treat appropriately. Pitted keratolysis is an associated disease of hyperhidrosis. It is a superficial bacterial skin infection causing pits of the stratum corneum, usually on the soles of the feet. The causative organism has been difficult to isolate but may be related to the Corynebacterium species. The clinical features one would see with pitted keratolysis are discrete crateriform defects ranging in size from 1 to 7 mm. These lesions may coalesce into areas of superficial erosion. The most common areas affected are the heels and balls of the feet. Usually, there will be a discoloration of the area or a “dirty” appearance, and a strong pungent odor. Treatment of pitted keratolysis involves aggressive control of the hyperhidrosis with Epsom salt foot soaks and topical therapy as described earlier in addition to the use of topical antibiotics, usually topical erythromycin solution 2%, (A/T/S®, Hoechst-Rousse). Use of oral antibiotics (erythromycin 1 gram daily) may be necessary if there is broad involvement of the plantar sole of the foot. What You Should Know About Systemic Therapy As the eccrine sweat glands are innervated by the sympathetic nervous system and stimulated through the release of acetylcholine, systemic medications such as anticholinergics and atropine-like drugs have a profound effect on secretion from the sweat duct but also have significant adverse side effects. The side effects of these drugs include dry mouth, blurred vision, urinary retention and constipation, and frequently necessitate discontinuation of the drugs. Some anticholinergic drugs such as propantheline bromide and glycopyrronium bromide (glycopyrrolate) are better tolerated as they do not cross the blood-brain barrier and therefore have fewer systemic side effects. Phenoxybenzamine is an alpha adrenergic blocking agent that has been used with some success but does have potential side effects on the sympathetic nervous system that may result in orthostatic hypotension and other reactions that are less desirable than the hyperhidrosis. Other systemic agents utilized without the sympathetic nervous system effects include the antidepressant amitriptyline, which has a mild sedative result as well as some anticholinergic action that can be helpful in cases of hyperhidrosis associated with significant emotional factors. The calcium channel blocker, diltiazem, has also shown some degree of effectiveness against hyperhidrosis by blocking the fluctuation of ions across the sweat duct necessary for the release of sweat. Indomethacin, a nonsteroidal antiinflammatory drug, may also be useful in low dosage (25 mg TID) by blocking prostaglandin E that is usually found in high concentration in sweat. Unfortunately, treating a localized problem of hyperhidrosis systemically frequently leads to undesirable side effects that will lead to discontinuation of the drug despite an improvement in symptoms. Is Iontophoresis A Viable Treatment Option? By definition, iontophoresis is the introduction of ions of soluble salts by means of an electric current into the tissues of the body for therapeutic purposes. It has been proven to be the simplest, safest and most cost-effective treatment for moderate to severe hyperhidrosis. The theory behind iontophoresis is that it alters the permeability of the secreting coil of the eccrine sweat gland and produces some epidermal injury that triggers abnormal keratinization and plug formation at the orifice of the sweat duct. The current is usually a direct current, although recent studies are evaluating the benefit and effectiveness of alternating current. One would usually perform this treatment with tap water but if sweating persists, clinicians can add other agents such as copper sulfate, aluminum sulfate, glycopyrrolate or hexapyrronium bromide or atropine sulfate. While using anticholinergic agents prolongs the period of anhidrosis, it also increases the risk of adverse side effects associated with the drug absorption. One should cover open areas on the skin or nails with petrolatum to avoid unnecessary discomfort. Advise the patient that there may be slight skin irritation after the treatment. One may see the formation of small vesicles or scaling, which quickly resolve. Treatment sessions usually last for 30 minutes daily at 10 to 20 mA for one week or until you achieve a desired level of dryness. With tap water, the desired result may last only a few weeks before requiring repeat sessions but if one adds an anticholinergic agent to the solution, the patient may remain anhidrotic for up to two months. The primary disadvantage to iontophoresis in treating hyperhidrosis is that the procedure is very time consuming. Patients can purchase portable home units, which are very effective and easy to use. Iontophoresis is not recommended in patients with cardiac arrhythmias or pacemakers, and it is contraindicated in pregnancy. Exploring Other Avenues Of Treatment The newest and probably the most discussed treatment modality for hyperhidrosis is the injection of botulinum toxin into the subcutaneous tissue. Botulinum toxin A (Botox®, Allergan) is a neurotoxin produced by the anaerobic bacteria Clostridium botulinum. It inhibits the release of acetylcholine from the presynaptic terminal of the neuromuscular junction of the striated muscle, leading to muscle weakness and paralysis within one to 14 days. Over three to four months, new neuromuscular junctions are formed and muscle function slowly returns. The toxin also facilitates the loss of sweating by inhibiting the release of acetylcholine from sympathetic nerves that innervate eccrine sweat glands with the effect lasting up to one year in some reports. There are no studies yet regarding botulinum injections of the sole of the foot for hyperhidrosis. Certainly one must consider some of the questionable adverse effects such as the generalized muscle weakness of the small intrinsic muscles of the hand and how these similar effects may affect the function of the foot. Other issues are the tremendous cost of the drug and the pain with the injections. More studies are needed to evaluate the outcomes of the injections and long-term side effects as well as to standardize the injection spacing needed and the dilution techniques. The botulinum toxin is contraindicated in cases of pregnancy, neuromuscular disorders such as myasthenia gravis and blood clotting disorders. Newer serotypes of botulinum toxin have recently been made available. Botulinum toxin B, which is known as Myobloc®, is one of seven different antigenic members of the botulinum toxin family. Trial studies thus far have revealed a tendency for botulinum toxin B to produce greater pain at the injection site and greater autonomic nervous system side effects such as dry mouth, dysphagia, dry eyes and urinary retention than one would see with botulinum toxin A. These are only preliminary findings and more studies are needed. Primary hyperhidrosis has a strong association with emotional stimuli and anxiety producing circumstances. Given this, biofeedback may play an effective role in reducing sweating by patients learning behavioral conditioning techniques. Preliminary results have shown a decreased incidence of sweating in some patients with this technique. However, long term follow-up results have not been published. One would reserve surgical sympathectomy for hyperhidrosis that is unresponsive to all forms of conservative or less invasive treatment. There are many consequences to sympathectomy and many of them are worse than the hyperhidrotic condition itself. In the lower extremity, L3 is the common location of a sympathectomy for plantar hyperhidrosis while the palmar and axillary regions are treated at the thoracic level T2 and T3. The adverse effects of a sympathectomy include phantom sweating, compensatory sweating and gustatory sweating. Phantom sweating is the sensation of impending hyperhidrosis in the absence of sweat. This can be very mentally disturbing to the patient. Compensatory sweating is an even greater dilemma as a patient will become hyperhidrotic in other areas of the body that were not a problem previously. This is by far the most common complication and poses the greatest challenge to treat. Chemical neurolysis has a similar although maybe not as permanent effect with the use of 100% ethanol or 6% phenol to create a sympathetic ganglion blockade. The effects can be dramatic with excessive dryness to the skin resulting in fissures and cracking. This radical form of treatment is rarely recommended or necessary to control primary hyperhidrosis. In Conclusion Hyperhidrosis can be both an annoying and a disabling condition. In cases of secondary hyperhidrosis, the treatment involves removing or controlling the underlying cause. The management of primary hyperhidrosis is more complex as the cause is not fully known or understood. Therefore, treatment involves reducing sweating to a level that is acceptable to the patient without making the cure worse than the condition itself. There are adverse effects with each of the different treatment modalities but often management is dictated by the location and severity of symptoms as well as patient compliance and expectations. The therapeutic options one offers to a patient should be tailored to the particular individual. Dr. Crawford is a Fellow of the American College of Foot and Ankle Surgeons and the American College of Foot and Ankle Pediatrics. She is board certified by the American Board of Podiatric Surgery and is Education Chair of the Northwest Podiatric Surgical Residency Program at the Swedish Medical Center, Providence Campus in Seattle. She is in private practice at the Ankle and Foot Clinic of Everett in Everett, Wash.
References 1. Abell E, Morgan K. The treatment of idiopathic hyperhidrosis by glycopyrronium bromide and top water iontophoresis. Br J Dermatol 1974; 91:87-91. 2. Akins DL, Meisenheimer JL, Dobson RL. Efficacy of Drionic unit in the treatment of hyperhidrosis. J Am Acad Dermatol 1987; 16:828-832. 3. Baumann LS, Halem ML. Botulinum toxin-B and the management of hyperhidrosis. Clin Dermatol 2004; 22:60-65. 4. Canaday BR, Stanford RH. Propantheline bromide in the management of hyperhidrosis associated with spinal cord injury. Ann Pharmacother 1995; 29:489-492. 5. Cheshire WP, Freeman R. Disorders of sweating. Semin Neurol 2003; 23 (4):399-406. 6. Connolly M, de Berker D. Management of primary hyperhidrosis: a summary of the different treatment modalities. Am J Clin Dermatol 2003; 4(10):681-697. 7. Cullen SI. Topical Methenamine therapy for hyperhidrosis. Arch Dermatol 1975; 111:1158-1160. 8. Dockery, G. Pediatric Dermatology, ch. 16, In: Cutaneous Disorders of the Lower Extremity. Philadelphia: WB Saunders, 1997: 277-279. 9. Duller P, Doyle Gentry W. Use of biofeedback in treating chronic hyperhidrosis: a preliminary report. Br J Dermatol 1980; 103:143-146. 10. Hashmonai M, Kopelman D, Assalia A. The treatment of primary palmar hyperhidrosis: a review. Surg Today 2000; 30:211-218. 11. Heckmann M, Ceballos-Baumann A, Plewig G. Botulinum toxin A for axillary hyperhidrosis (excessive sweating). N Engl J Med 2001; 344:488-493. 12. Holzle E, Alberti N. Long-term efficacy and side effects of tap water iontophoresis of palmoplantar hyperhidrosis—the usefulness of home therapy. Dermatologica 1987; 175:126-135. 13. Holzle E, Braun-Falco O. Structural changes in axillary eccrine glands following long-term treatment with aluminum chloride hexahydrate solution. Br J Dermatol 1984; 110:399-403. 14. Klein AW. Complications with the use of botulinum toxin. Dermatol Clin 2004; 22:197-205. 15. Kobayashi K, Omote K, Homma E, et al. Sympathetic ganglion blockade for the management of hyperhidrosis. J Dermatol 1994; 21:575-581. 16. Lowe NJ, Yamauchi PS, Lask GP, et al. Efficacy and safety of botulinum toxin type a in the treatment of palmar hyperhidrosis: a double-blind, randomized, placebo-controlled study. Dermatol Surg 2002; 28(9):822-827. 17. Naumann M, Lowe NJ. A randomized, placebo controlled trial, double-blind study of botulinum toxin type A in bilateral axillary hyperhidrosis. BMJ 2001; 323:596-599. 18. Nyamekye IK. Current therapeutic options for treating primary hyperhidrosis. Eur J Vasc Endovasc Surg 2004; 27:571-576. 19. Odderson IR. Hyperhidrosis treated by botulinum A exotoxin. Dermatol Surg 1998; 24:1237-1241. 20. Pernet G. Symmetrical lividities of the soles of the feet. Br J Dermatol 1925; 37:123-125. 21. Reinauer S, Neusser A, Schauf G, et al. Iontophoresis with alternating current and direct current offset (AC/DC iontophoresis): a new approach for the treatment of hyperhidrosis. Br J Dermatol 1993; 129:166-169. 22. Rietschel RL, Carr JF, Lewis CW. Symmetrical lividity of the palm and soles. Int J Dermatol 1978; 17:739-744. 23. Rusciani L, Severino E, Rusciani A. Type A botulinum toxin: a new treatment for axillary and palmar hyperhidrosis. J Drugs Dermatol 2002; 1:147-151. 24. Sato K, Ohtsuyama M, Samman G. Eccrine sweat gland disorders. J Am Acad Dermatol 1991; 24:1010-1014. 25. Schnider P, Binder M, Auff E, et al. Double-blind trail of botulinum A toxin for the treatment of focal hyperhidrosis of the palms. Br J Dermatol 1997; 136:548-552. 26. Schnider P, Moraru E, Kittler H, et al. Treatment of focal hyperhidrosis with botulinum toxin type A: long-term follow-up in 61 patients. Br J Dermatol 2001; 145:289. 27. Seukeran DC, Highet AS. The use of topical glycopyrrolate in the treatment of hyperhidrosis: report of a case and review of the literature. Clin Exp Dermatol 1998; 23:204-205. 28. Shaw JE, Abbott CA, Tindle K, et al. A randomized controlled trial of topical glycopyrrolate, the first specific treatment for diabetic gustatory sweating. Diabetologia 1997; 40:229-301. 29. Shelley WB, Shelley ED. Symmetrical lividity of the soles. Cutis 2002; 70:12-13. 30. Shelley WB, Talanin NY, Shelley ED. Botulinum toxin therapy for palmar hyperhidrosis. J Am Acad Dermatol 1998; 38:227-229. 31. Shimizu H, Yasuhiko T, Shimiz J, et al. Effectiveness of iontophoresis with alternating current (AC) in the treatment of patients with palmoplantar hyperhidrosis. J Dermatol 2003; 30:444-449. 32. Solomon B, Hayman R. Botulinum toxin type A therapy for palmar and digital hyperhidrosis. J Am Acad Dermatol 2000; 42:1026-1029. 33. Susak A, Minkov R, Isakov E. The use of Methenamine as an antiperspirant for amputees. Pros and Orth Int 1996; 20:172-175. 34. Swartling C, Farnstrand C, Abt G, et al. Side-effects of intradermal injections of botulinum A toxin in the treatment of palmar hyperhidrosis: a neurophysiological study. Eur J Neurol 2001; 8:451-456. 35. Thomas I, Brown J, et al. Palmoplantar hyperhidrosis: a therapeutic challenge. Am Fam Phys 2004; 69(5):1117-1120.