Hyperhidrosis may be defined as excessive sweating, beyond a level required to maintain normal body temperature in response to heat exposure or exercise. Hyperhidrosis can be classified as either primary or secondary. Primary hyperhidrosis is idiopathic in nature, typically involving the hands (palmar), feet (plantar), or axillae. Secondary hyperhidrosis can result from a variety of drugs, such as tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), or underlying diseases/conditions, such as febrile diseases, diabetes mellitus, or menopause. Gustatory hyperhidrosis is an unusual iatrogenic cause of facial hyperhidrosis in response to hot or spicy foods, resulting from surgery to the parotid gland and subsequent aberrant regenerating parasympathetic fibers.

The consequences of hyperhidrosis are primarily psychosocial in nature. Excessive sweating may be socially embarrassing (i.e., limiting the ability to shake hands) or interfere with certain professions. For example, palmar hyperhidrosis may preclude artwork, working with electrical components, or playing certain musical instruments. In addition, hyperhidrosis may require several changes of clothing a day; excessive sweating may also result in staining of clothing or shoes.

Treatment of secondary hyperhidrosis naturally focuses on treatment of the underlying cause, such as discontinuing certain drugs or hormone replacement therapy as a treatment of menopausal symptoms. A variety of therapies have been investigated for primary hyperhidrosis, including topical therapy with aluminum chloride or tanning agents, iontophoresis, botulinum toxin, endoscopic transthoracic sympathectomy, and surgical excision of axillary sweat glands. Botulinum toxin has also been investigated as a treatment of secondary gustatory hyperhidrosis. In terms of botulinum toxin, this policy only discusses its use as a treatment of hyperhidrosis. Other indications for botulinum toxin are discussed separately in policy No. 5.01.05.

Primary Hyperhidrosis

Treatment of primary hyperhidrosis may be considered medically necessary only in the small subset of patients with medical complications, such as skin maceration with secondary infections or significant functional impairments. Treatment with endoscopic transthoracic sympathectomy and surgical excision of axillary sweat glands may be considered only if conservative treatment (e.g., aluminum chloride or botulinum toxin) has failed.

Iontophoresis and axillary liposuction are considered investigational as a treatment for primary hyperhidrosis.

In the majority of patients, treatment of primary hyperhidrosis would be considered not medically necessary based on the lack of functional impairment or medical complications associated with the condition.

Secondary Gustatory Hyperhidrosis

Botulinum toxin is considered an effective treatment of gustatory hyperhidrosis. Its coverage eligibility may be related to specific contract language regarding reconstructive services (see Benefit Application).

A multi-specialty working group defines primary focal hyperhidrosis as a condition that is characterized by visible, excessive sweating of at least 6 months’ duration without apparent cause and with at least 2 of the following features: bilateral and relatively symmetric sweating, impairment of daily activities, frequency of at least once per week, age at onset younger than 25 years, positive family history, and cessation of focal sweating during sleep. (1)
In the hyperhidrosis disease severity scale, patients rate the severity of symptoms on a scale of 1-4: (2)
1. My underarm sweating is never noticeable and never interferes with my daily activities.
2. My underarm sweating is tolerable but sometimes interferes with my daily activities.
3. My underarm sweating is barely tolerable and frequently interferes with my daily activities.
4. My underarm sweating is intolerable and always interferes with my daily activities.

A variety of iontophoretic devices can be purchased for use in the home. There are no specific HCPCS codes for these pieces of DME. Code E1399 (Durable medical equipment, miscellaneous)
Botulinum toxin may be coded for using HCPCS code J0585 (Botulinum toxin, type A, per unit).

BlueCard/National Account Issues

For treatment of secondary gustatory hyperhidrosis, Plans may want to review their contractual language regarding reconstructive surgery. Interpretation of contractual definitions of reconstructive surgery is discussed more thoroughly in policy No. 10.01.09.

Aluminum chloride

Aluminum chloride is a common component of over-the-counter antiperspirants, although a prescription product is available (Drysol). Although the mechanism is unclear, aluminum chloride is associated with atrophy of the secretory cells seen in eccrine sweat glands. Aluminum chloride is predominantly used to treat axillary hyperhidrosis and not palmar or volar hyperhidrosis.

Iontophoresis

Iontophoresis is a technique that involves the use of an electric current to introduce various ions through the skin.

The mechanism of action is not precisely known, but is thought to be related to plugging of the sweat gland pores. The typical device consists of trays containing electrodes. Prior to using, the trays are filled with tap water, the patient inserts the hands or feet or positions the device in the axilla, and the current is turned on. Patients are treated for approximately 20 minutes, with treatments every 2 to 3 days for 5 to 10 sessions before an effect is observed. Maintenance therapy may be applied every 2 weeks after initial therapy.

Iontophoresis in conjunction with tap water or anticholinergic agents is a longstanding treatment of palmar or plantar and more recently axillary idiopathic hyperhidrosis, with a reported success rate of up to 85%. (3). However, the published literature regarding iontophoresis as a treatment of hyperhidrosis is sparse. A 2003 TEC Assessment on iontophoresis concluded that evidence was insufficient to determine whether the effects of iontophoresis for the treatment of hyperhidrosis exceed those of placebo. (4) The 2003 TEC Assessment also concluded that, in the treatment of hyperhidrosis, there is insufficient evidence to show that tap water iontophoresis is as beneficial as topical drug administration. The conclusions of the TEC Assessment form the rationale for the change in the policy statement, which in the original suggested that iontophoresis could be considered medically necessary.

Botulinum toxin

Botulinum toxin is a potent neurotoxin that blocks cholinergic nerve terminals; symptoms of botulism include cessation of sweating. Therefore, intracutaneous injections have been investigated at a treatment of gustatory hyperhidrosis and focal primary hyperhidrosis, most frequently involving the axillae or palms. Laskawi and colleagues reported on the outcomes of 19 patients with gustatory hyperhidrosis treated with botulinum toxin injected into every 4 cm-2 of involved skin. (5) In all cases, gustatory sweating ceased within 2 days, with a mean duration of effect of 17 months. There is a considerable body of published literature regarding botulinum toxin injection of the treatment of axillary hyperhidrosis, all of which substantiates its effectiveness. (6-15) Two of these were double-blind, randomized trials that demonstrated that botulinum toxin was more effective than placebo in patients with palmar hyperhidrosis (5,11). The drawback of this approach is the need for repeated injections, which have led some to consider surgical approaches, discussed here.

Endoscopic Transthoracic Sympathectomy

Eccrine sweat glands produce an aqueous secretion, the overproduction of which is primarily responsible for hyperhidrosis. These glands are innervated by the sympathetic nervous system. Therefore, various surgical techniques of thoracic sympathectomy have been investigated as a curative procedure, primarily for combined palmar and axillary hyperhidrosis. Large case series have reported success rates of up to 98% in large case series. (16-22) A variety of approaches have been reported but endoscopic techniques have emerged as a minimally invasive alternative to a transaxillary, supraclavicular, or anterior thoracic approach. While accepted as an effective treatment, sympathectomy is not without complications. In addition to the immediate surgical complications of pneumothorax or temporary Horner’s syndrome, compensatory sweating on the trunk can occur in up to 55% of patients, reducing patient satisfaction with the procedure. Gustatory sweating may also occur. Sympathectomy also results in cardiac sympathetic denervation, which in turn can lead to a 10% reduction in the heart rate.

Surgical Removal of Axillary Sweat Glands

Both eccrine and apocrine axillary sweat glands are predominantly located in the superficial subcutis and dermal subcutaneous interface, with scattered eccrine glands located completely in the dermis. Surgical removal has been performed in patients with severe isolated axillary hyperhidrosis. Removal may involve removal of the subcutaneous sweat glands without removal of any skin, limited excision of skin and removal of surrounding subcutaneous sweat glands, or a more radical excision of skin and subcutaneous tissue en bloc. (23) Depending on the completeness of surgical excision, the treatment is effective in from 50%–95% of patients. Liposuction has also been investigated as a minimally invasive technique to surgical excision. In some case, the procedure has been performed to remove the apocrine sweat glands, located deeper in the dermis, and responsible for axillary malodor, which may be referred to as osmidrosis, or bromidrosis if the malodor is also associated with hyperhidrosis. Although this procedure has been performed for several decades, only scattered case reports regarding its effectiveness were identified in a MEDLINE literature search. (24-28)

2008 Update
A search of the MEDLINE database for studies published from 2005 through January 2008 indicates continued interest in the use of botulinum toxin to treat hyperhidrosis. Allergan funded a multicenter double-blind, randomized, placebo-controlled efficacy and safety study of botulinum toxin type A (BTX-A, 0, 50 or 75 U) in 322 subjects with persistent bilateral primary axillary hyperhidrosis (e.g., exhibiting at least 2 of the following: bilateral sweating, impairment of daily activities, frequency of at least once per week, < 25 years of age at onset, positive family history, and cessation of focal sweating during sleep). (29) Enrollment criteria included a resting sweat production of at least 50 mg/axilla in 5 minutes and a rating of 3 or 4 (underarm sweating barely tolerable or intolerable, and frequently or always interferes with daily activities) on the Hyperhidrosis Disease Severity Scale (HDSS). Retreatment after 4 weeks was allowed in subjects with at least 50 mg of sweat (per axilla) over 5 minutes and an HDSS score of 3 or 4. Following the first injection, 75% of subjects in the BTX-A groups showed at least a 2 point improvement in the HDSS, compared with 25% of subjects in the placebo group. Sweat production decreased by 87% (75 U), 82% (50 U), and 33% (vehicle). (Similar results were obtained in patients requiring a second treatment). The median duration of effect was 197, 205, and 96 days (75-U, 50-U, and vehicle, respectively). Seventy eight percent of subjects (252) completed the 52-week study; 96/110 (87%) in the 75-U group, 83/104 (80%) in the 50-U group, and 73/108 (68%) in the control group. Intent-to-treat analysis at 52-weeks showed a responder rate (> 2 points on the HDSS) for 54 (49%) subjects in the 75-U group, 57 (55%) in the 50-U group, and 6 (6%) in the placebo group. Injection-site pain was reported in about 10% of all groups, with a mean duration of 2.4 days (10 day maximum). A topical preparation of botulinum toxin A was studied in a small (12 patient) vehicle-controlled split-side trial. (29) At 4 weeks, sweat production was reduced by 65% with topical application of BTX-A vs. 25% on the vehicle-treated side. Additional studies with a larger number of subjects and longer follow-up are needed to assess this new formulation.

References:

1. Hornberger J, Grimes K, Naumann M et al; Multi-Specialty Working Group on the Recognition, Diagnosis, and Treatment of Primary Focal Hyperhidrosis. Recognition, diagnosis, and treatment of primary focal hyperhidrosis. J Am Acad Dematol 2004; 51(2):274-86.
2. Solish N, Bertucci V, Dansereau A et al; Canadian Hyperhidrosis Advisory Committee. A comprehensive approach to the recognition, diagnosis, and severity-based treatment of focal hyperhidrosis: recommendations of the Canadian Hyperhidrosis Advisory Committee. Dermatol Surg 2007; 33(8):908-23.
3. Levit F. Treatment of hyperhidrosis by tap water iontophoresis. Cutis 1980; 26(2):192-4.
4. 2003 TEC Assessment. Iontophoresis for Medical Indications.
5. Laskawi R, Drobik C, Schonebeck C. Up-to-date report of botulinum toxin type A treatment in patients with gustatory sweating (Frey’s syndrome). Laryngoscope 1998; 108(3):381-4.
6. Schnider P, Binder M, Auff E et al. Double-blind trial of botulinum A toxin for the treatment of focal hyperhidrosis of the palms. Br J Dermatol 1997; 136(4):548-52.
7. Shelley WB, Talanin NY, Shelley ED. Botulinum toxin therapy for palmar hyperhidrosis. J Am Acad Dermatol 1998; 38(2 pt 1):227-9.
8. Naumann M, Hofmann U, Bergmann I et al. Focal hyperhidrosis: effective treatment with intracutaneous botulinum toxin. Arch Dermatol 1998; 134(3):301-4.
9. Naumann MK, Hamm H, Lowe NJ. Effect of botulinum toxin type A on quality of life measures in patients with excessive axillary sweating: a randomized controlled trial. Br J Dermatol 2002; 147(6):1218-26.
10. Nauman M, Lowe NJ, Kumar CR et al. Botulinum toxin type A is a safe and effective treatment for axillary hyperhidrosis over 16 months: a prospective study. Arch Dermatol 2003; 139(6):731-6
11. Campanati A, Penna L, Guzzo T et al. Quality-of-life assessment in patients with hyperhidrosis before and after treatment with botulinum toxin: results of an open-label study. Clin Ther 2003; 25(1):298-308.
12. 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):822-7.
13. Saadia D, Voustianiouk A, Wang AK et al. Botulinum toxin type A in primary palmar hyperhidrosis: randomized, single-blind, two-dose study. Neurology 2001; 57(11):2095-9.
14. Naumann M, Lowe NJ. Botulinum toxin type A in treatment of bilateral primary axillary hyperhidrosis: randomised, parallel group, double blind, placebo controlled trial. BMJ 2001; 323(7313):596-9.
15. Heckmann M, Ceballos-Baumann AO, Plewig G. Botulinum toxin A for axillary hyperhidrosis (excessive sweating). N Engl J Med 2001; 344(7):488-93.
16. Drott C, Gothberg G, Claes G. Endoscopic transthoracic sympathectomy: an efficient and safe method for the treatment of hyperhidrosis. J Am Acad Dermatol 1995 Jul; 33(1):78-81.
     
17. Shachor D, Jedeikin R, Olsfanger D et al. Endoscopic transthoracic sympathectomy in the treatment of primary hyperhidrosis. A review of 290 sympathectomies. Arch Surg 1994; 129(3):241-4.
18. Gossot D, Galetta D, Pascal A et al. Long-term results of endoscopic thoracic sympathectomy for upper limb hyperhidrosis. Ann Thorac Surg 2003; 75(4):1075-9.
19. Leseche G, Castier Y, Thabut G et al. Endoscopic transthoracic sympathectomy for upper limb hyperhidrosis: limited sympathectomy does not reduce postoperative compensatory sweating. J Vasc Surg 2003; 37(1):124-8.
20. Atkinson JL, Fealey RD. Sympathotomy instead of sympathectomy for palmar hyperhidrosis: minimizing postoperative compensatory hyperhidrosis. Mayo Clin Proc 2003; 78(2):167-72.
21. Lin TS, Kuo SJ, Chou MC. Uniportal endoscopic thoracic sympathectomy for treatment of palmar and axillary hyperhidrosis: Analysis of 2000 cases. Neurosurgery 2002; 51(5 suppl):84-7.
22. Han PP, Gottfried ON, Kenny KJ et al. Biportal thoracoscopic sympathectomy: surgical techniques and clinical results for the treatment of hyperhidrosis. Neurosurgery 2002; 50(2):306-12.
23. Hafner J, Beer GM. Axillary sweat gland excision. Curr Probl Dermatol 2002; 30:57-63.
24. Park S. Very superficial ultrasound-assisted lipoplasty for the treatment of axillary osmidrosis. Aesthetic Plast Surg 2000; 24(4):275-9.
25. Tsai RY, Lin JY. Experience of tumescent liposuction in the treatment of osmidrosis. Dermatol Surg 2001; 27(5):446-8.
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27. Shenaq SM, Spira M, Christ J. Treatment of bilateral axillary hyperhidrosis by suction-assisted lipolysis technique. Ann Plast Surg 1987; 19(6):548-51.
28. Ong WC. Lim TC, Lim J et al. Suction-curettage: treatment for axillary hyperhidrosis and hidradenitis. Plast Reconstr Surg 2003; 111(2):958-9.
29. Lowe NJ, Glaser DA, Eadie N et al; North American Botox in Primary Axillary Hyperhidrosis Clinical Study Group. Botulinum toxin type A in the treatment of primary axillary hyperhidrosis: a 52-week multicenter double-blind, randomized, placebo-controlled study of efficacy and safety. J Am Acad Dermatol 2007; 56(4):604-11.
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Botulinum Toxin, as Treatment of Hyperhidrosis
Endoscopic Sympathectomy
Gustatory Hyperhidrosis
Hyperhidrosis
Iontophoresis, as Treatment of Hyperhidrosis
Sweating, Excessive
Sympathectomy, Thoracic
Thoracoscopic Sympathectomy