| MP 8.01.19 | Treatment of Hyperhidrosis | |
| Medical Policy | ||
| Section Therapy |
Original Policy Date 7/16/99 |
Last Review Status/Date Reviewed with literature search/8:2009 |
| Issue 8:2009 |
Return to Medical Policy Index |
Disclaimer
Our medical policies are designed for informational purposes only and are not an authorization, or an explanation of benefits, or a contract. Receipt of benefits is subject to satisfaction of all terms and conditions of the coverage. Medical technology is constantly changing, and we reserve the right to review and update our policies periodically.
Description
Hyperhidrosis may be defined as excessive sweating, beyond a level required to maintain normal body temperature in response to heat exposure or exercise. It can be classified as either primary or secondary. Primary localized hyperhydrosis is idiopathic in nature, typically involving the hands (palmar), feet (plantar), or axillae (underarms). Secondary hyperhydrosis 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. Secondary hyperhydrosis is usually generalized or craniofacial sweating. Secondary gustatory hyperhydrosis is excessive sweating on ingesting highly spiced foods. This trigeminovascular reflex typically occurs symmetrically on scalp or face and predominately over forehead, lips, and nose. Secondary facial gustatory sweating, in contrast, is usually asymmetrical and occurs independently of the nature of the ingested food. This phenomenon frequently occurs after injury or surgery in the region of the parotid gland. Frey’s syndrome is an uncommon type of secondary gustatory hyperhydrosis that arises from injury to or surgery near the parotid gland resulting in damage to the secretory parasympathetic fibers of the facial nerve. After injury, these fibers regenerate and miscommunication occurs between them and the severed postganglionic sympathetic fibers that supply the cutaneous sweat glands and blood vessels. The aberrant connection results in gustatory sweating and facial flushing with mastication. Aberrant secondary gustatory sweating follows up to 73% of surgical sympathectomies and is particularly common after bilateral procedures.
The consequences of hyperhydrosis are primarily psychosocial in nature. Symptoms such as fever, night sweats, or weight loss require further investigation to rule out secondary causes. Sweat production can be assessed with the minor starch iodine test, which is a simple qualitative measure to identify specific sites of involvement.
A variety of therapies have been investigated for primary hyperhydrosis, including topical therapy with aluminum chloride, iontophoresis, intradermal injections of botulinum toxin type A, endoscopic transthoracic sympathectomy, and surgical excision of axillary sweat glands. Treatment of secondary hyperhydrosis focuses on treatment of the underlying cause, such as discontinuing certain drugs or hormone replacement therapy as a treatment of menopausal symptoms.
The outcome of different surgical and medical treatment modalities is best assessed by using a combination of tools. Quantitative tools include gravimetry, evaporimetry, and Minor's starch and iodine test. Qualitative assessment tools include general health surveys and hyperhydrosis -specific surveys. Of these, the Hyperhidrosis Disease Severity Scale (HDSS) has been found to have a good correlation to other assessment tools and to be practical in the clinical setting.
Drysol™ (aluminum chloride [hexahydrate] 20% topical solution, Person and Covey, Inc.) is FDA approved as an astringent to be used as an aid in the management of hyperhidrosis (axillae, palmar, plantar, and craniofacial) available by prescription. In 2004 the U.S. Food and Drug Administration (FDA) approved botulinum toxin type A to treat primary axillary hyperhydrosis (severe underarm sweating) that cannot be managed by topical agents such as prescription (Drysol™) and over-the-counter (OTC) (i.e., Certain Dri® 12%) topical agents with aluminum chloride. A typical dosage would be intradermal injections of 50 units per axilla. Efficacy begins in about 7 to 10 days and lasts approximately 4 to 12 months. Contraindications to botulinum type A toxin include infection at the proposed injection site(s), pregnancy, and lactation. Botulinum toxin type A should be used with caution in patients with neuromuscular disorders (i.e., myasthenia gravis) and patients taking medications such as aminoglycosides, pencillamine, quinine, and calcium channel blockers. The safety and effectiveness has been established for patients 18 years and older. Botulinum toxin has also been investigated as a treatment of hyperhydrosis in body areas other than the axilla and for secondary gustatory hyperhydrosis.
On February 8, 2008, the FDA issued an Early Communication about the Ongoing Safety Review; Botox and Botox Cosmetic FDA (botulinum toxin type A) and Myobloc (botulinum type B). The FDA has received reports of systemic adverse reactions including respiratory compromise and death following the use of botulinum toxins types A and B for both FDA-approved and unapproved uses. The reactions reported are suggestive of botulism, which occurs when botulinum toxin spreads in the body beyond the site where it was injected. The most serious cases had outcomes that included hospitalization and death, and occurred mostly in children treated for cerebral palsy-associated limb spasticity. Use of botulinum toxins for treatment of limb spasticity (severe arm and leg muscle spasms) in children or adults is not an approved use in the United States. The communication stated; “The safety, efficacy and dosage of botulinum toxins have not been established for the treatment of limb spasticity of cerebral palsy or for use in any condition in children less than 12 years of age”. The FDA will update this document when additional information or analyses become available. (1)
On July 31, 2009, the FDA approved the following revisions to the prescribing information of Botox/Botox Cosmetic and Myobloc:
- “A Boxed Warning highlighting the possibility of experiencing potentially life-threatening distant spread of toxin effect from injection site after local injection.
- A Risk Evaluation and Mitigation Strategy (REMS) that includes a Medication Guide to help patients understand the risk and benefits of botulinum toxin products.
- Changes to the established drug names to reinforce individual potencies and prevent medication errors. The potency units are specific to each botulinum toxin product, and the doses or units of biological activity cannot be compared or converted from one product to any other botulinum toxin product. The new established names reinforce these differences and the lack of interchageability among products.”
AbobotulinumtoxinA, marketed as Dysport, was approved on April 29, 2009 and prescribing information included the Boxed Warning, REMS and new drug name at the time of approval.
Summary of FDA-Approved Botulinum Toxin Products
Trade Name* |
New Drug Name |
Old Drug Name |
Indications |
Botox |
OnabotulinumtoxinA |
Botulinum toxin type A | cervical dystonia, severe primary axillary hyperhidrosis, strabismus, blepharospasm |
Botox Cosmetic |
OnabotulinumtoxinA |
Botulinum toxin type A | temporary improvement in the appearance of moderate to severe glabellar lines |
Dysport |
AbobotulinumtoxinA |
Botulinum toxin type A | cervical dystonia, temporary improvement in the appearance of moderate to severe glabellar lines |
Myobloc |
RimabotulinumtoxinB |
Botulinum toxin type B | cervical dystonia |
*The marketed trade names and product formulations have not changed.
Related Policies
This policy discusses botulinum toxin type A and type B as a treatment of hyperhidrosis. Other indications for botulinum toxin are discussed separately in policy No. 5.01.05.
This policy discusses botulinum toxin type A and type B as a treatment of hyperhidrosis. Other indications for botulinum toxin are discussed separately in policy No. 5.01.05.
This policy only discusses iontophoresis as a treatment of hyperhidrosis. Other indications for iontophoresis are discussed separately in policy No. 8.03.14.
Policy
Primary Focal Hyperhidrosis
Primary focal hyperhidrosis is defined as excessive sweating induced by sympathetic hyperactivity in selected areas that is not associated with an underlying disease process. The most common locations are underarms (axillary hyperhidrosis), palms (palmar hyperhidrosis), soles (plantar hyperhidrosis) or face (craniofacial hyperhidrosis).
- acrocyanosis of the hands;
- history of recurrent skin maceration with bacterial or fungal infections;
- history of recurrent secondary infections;
- history of persistent eczematous dermatitis in spite of medical treatments with topical dermatological or systemic anticholinergic agents.
| Focal Regions | Treatments considered Medically Necessary | Treatments considered Investigational |
| Axillary |
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| Palmar |
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| Plantar |
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| Craniofacial |
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Secondary Hyperhidrosis
Secondary hyperhidrosis is excessive sweating that can be generalized or craniofacial sweating and may occur as a result of olfactory or gustatory stimuli, neurologic lesions, intrathoracic neoplasms, Raynaud’s disease and Frey’s syndrome.
The following treatments would be considered medically necessary for the treatment of severe gustatory hyperhidrosis:
- aluminum chloride 20% solution*
- surgical options (i.e., tympanic neurectomy), if conservative treatment has failed.
The following treatments are considered investigational as a treatment for severe gustatory hyperhidrosis including, but not limited to:
- OnabotulinumtoxinA and RimabotulinumtoxinB are considered investigational for treatment of gustatory hyperhidrosis. (See Policy Guidelines for list of conditions)
- iontophoresis
* FDA approved indication
Policy Guidelines
A multispecialty 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. (2)
In the hyperhidrosis disease severity scale, patients rate the severity of symptoms on a scale of 1-4: (3)
- My underarm sweating is never noticeable and never interferes with my daily activities.
- My underarm sweating is tolerable but sometimes interferes with my daily activities.
- My underarm sweating is barely tolerable and frequently interferes with my daily activities.
- 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 codes: J0585 OnabotulinumtoxinA, per unitJ0587 RimabotulinumtoxinB, per 100 units
Benefit Application
BlueCard/National Account Issues
State or federal mandates (e.g., FEP) may dictate that all FDA approved devices, drugs, or biologics may not be considered investigational and thus these devices may be assessed only on the basis of their medical necessity.
In this document, procedures are considered reconstructive when intended to address a significant variation from normal related to accidental injury, disease, trauma, treatment of a disease or congenital defect. NOTE: Not all benefit contracts include benefits for reconstructive services as defined by this document. Benefit language supersedes this document. Non-surgical agents may be covered under pharmacy benefit.Rationale
On July 31, 2009, the FDA approved revisions to the prescribing information of Botox and Myobloc that included changes to the established drug names. The policy Description section and policy statements have been updated to reflect these revisions. However, the articles detailed below have not been modified.
Hyperhidrosis treatments include topical, systemic, nonsurgical, and surgical methods. Treatment options vary in their indication for use, therapeutic efficacy, duration of effect, and side effects. Antiperspirants containing aluminum salts, Drysol™ (aluminum chloride hexahydrate 20% topical solution, Person and Covey, Inc.), are considered the most effective topical agents for mild focal axillary hyperhidrosis and are used as first-line agents for focal hyperhidrosis in all locations. The aluminum salts obstruct the eccrine sweat gland pore to cause temporary anhydrosis. Irritation to skin is the main limiting side effect and can be minimized by applying the antiperspirant to dried areas at bedtime.
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%. (4). 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. (5) The 2003 TEC Assessment also concluded that, in the treatment of hyperhidrosis, evidence is insufficient 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.
A small pilot study (n =17) (6) examined the use of subdermal Nd-YAG laser as an option for the treatment of axillary hyperhidrosis. Patients with axillary hyperhidrosis were treated using a subdermal 1,064-nm Nd-YAG laser. The follow-up was 8 weeks following the procedure. Patients with previous surgical treatment were excluded. The primary endpoints were reduction of hyperhidrotic activity and patient and physician satisfaction with the procedure. The subdermal laser-assisted axillary hyperhidrosis treatment resulted in clinical improvement. The mean area of sweating was reduced from 63 plus 15 to 15 plus 18cm2. Patient global assessment showed an excellent result in 12 cases (70.6%), a good result in 3 cases (17.6%), and a fair result in 2 patients (11.8%). Physician global assessment was excellent in 10 patients (58.8%), good in 4 patients (23.5%), and fair in 3 patients (17.6%). In conclusion, the treatment of axillary hyperhidrosis using the 1,064-nm Nd-YAG laser has the advantage of performing a minor invasive procedure without leaving large scars and causing temporary impairment. Although this small study without a control group appears promising, evidence is insufficient to determine the impact on clinical outcomes.
Botulinum toxin type A (Botox®, Allergan Inc.) (7) is a potent neurotoxin that blocks cholinergic nerve terminals; symptoms of botulism include cessation of sweating. Therefore, intracutaneous injections have been investigated as 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 as a result of Frey’s syndrome treated with botulinum toxin injected into every 4 cm2 of involved skin. (8) In all cases, gustatory sweating ceased within 2 days, with a mean duration of effect of 17 months. A considerable body of published literature addresses botulinum toxin injection of the treatment of axillary hyperhidrosis, all of which substantiates its effectiveness. (9-18) Two of these were double-blind, randomized trials that demonstrated that botulinum toxin was more effective than placebo in patients with palmar hyperhidrosis (8, 14). The drawback of this approach is the need for repeated injections, which have led some to consider surgical approaches, discussed here.
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. The second (T2) and third (T3) thoracic ganglia are responsible for palmar hyperhidrosis, the fourth (T4) thoracic ganglion controls axillary hyperhidrosis, and the first (T1) thoracic ganglion controls facial hyperhidrosis. Various surgical techniques of thoracic sympathectomy have been investigated as a curative procedure, primarily for combined palmar and axillary hyperhidrosis that is unresponsive to topical, systemic and botulinum toxin type A therapy.
Large case series have reported success rates of up to 98% in large case series. (19-25) 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. In addition to the complications associated with sympathectomy, lumbar sympathectomy is not employed for plantar hyperhidrosis because of the additional risk of permanent sexual dysfunction in men and women. (26)
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. Surgery 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. (27) 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. (28-32)
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, younger than 25 years of age at onset, positive family history, and cessation of focal sweating during sleep). (33) 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 of 110 (87%) in the 75-U group, 83 of 104 (80%) in the 50-U group, and 73 of 108 (68%) in the control group. Intent-to-treat analysis at 52 weeks showed a responder rate (greater than 2-point improvement 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. (34) At 4 weeks, sweat production was reduced by 65% with topical application of BTX-A versus 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.
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, younger than 25 years of age at onset, positive family history, and cessation of focal sweating during sleep). (33) 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 of 110 (87%) in the 75-U group, 83 of 104 (80%) in the 50-U group, and 73 of 108 (68%) in the control group. Intent-to-treat analysis at 52 weeks showed a responder rate (greater than 2-point improvement 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. (34) At 4 weeks, sweat production was reduced by 65% with topical application of BTX-A versus 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.
2009 Update
A search of the MEDLINE database was conducted for the period January 2008 through December 2008 to update this policy. The use of botulinum type A for glandular hypersecretory disorders and the optimal surgical technique for hyperhidrosis continues to be of interest. However, few long-term, randomized clinical comparative trials exist for the treatment of hyperhidrosis conditions.
Technology Assessments and Systematic Reviews
In May 2008, a report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology was published. (35) The assessment is an evidence-based review of the safety and efficacy of botulinum neurotoxin type A in the treatment of autonomic and urologic disorders and low back and head pain. The conclusions and recommendations were developed based on the highest level of evidence and put into current clinical context. The literature quality available for the hyperhidrosis indications was as follows: axillary hyperhidrosis (2 randomized controlled studies); palmar hyperhidrosis (1 randomized control trial and several small clinical studies) and gustatory sweating (5 small controlled clinical trials). In conclusion, the American Academy of Neurology (AAN) created guidelines for use of botulinum neurotoxin for the treatment of autonomic disorders and pain. These guidelines include the following recommendations for hyperhidrosis; axillary hyperhidrosis, strong evidence supports botulinum toxin type A should be offered as a treatment option; palmar hyperhidrosis, good evidence supports botulinum toxin type A should be considered as a treatment option to patients who are unresponsive to topical treatment as an alternative to iontophoresis or sympathectomy; and gustatory hyperhidrosis; weak evidence supports botulinum toxin type A as a treatment option for gustatory sweating.
In conclusion, the current evidence evaluating botulinum toxin type A use for gustatory hyperhidrosis as a result of Frey’s syndrome includes 4 non-controlled trials; a cohort study and 3 open trials, and 3 case reports all showing favorable treatment outcomes. The patient inclusion criteria was variable across the studies and case reports; ages varied (16 to 87 years); patients had undergone varied types of parotid surgery (i.e., bilateral, partial); not all studies documented gustatory sweating with Minor’s starch test as part of the patient screening; 1 case report and a cohort study included patients who were refractory to topical agents and surgery. In spite of what appears to be promising clinical efficacy and safety, there are no randomized controlled trials or head-to-head comparisons with other treatment options and numerous limitations in the current evidence. These limitations include small study group size and variability in patient inclusion and exclusion criteria, dose (which makes it difficult to assess the optimal one), outcomes measures for determining clinical efficacy, and follow-up time periods to evaluate long-term efficacy. Therefore, the evidence is insufficient to draw conclusions on the short- and long-term clinical effectiveness of botulinum type A for gustatory hyperhidrosis as a result of Frey’s syndrome.
Review articles by Clayman et al. (36) and deBree et al. (37) describe the various medical and surgical treatments for Frey’s syndrome. Tympanic neurectomy is described as a treatment for Frey’s syndrome with satisfactory control reported in 82% of patients. In addition, this surgical treatment is generally definitive without a need for repeated interventions.
A randomized, controlled comparative trial (38) included only male patients (n =80), with a mean age of 22. years, undergoing bilateral thoracoscopic sympathectomy or sympathetic blockage to treat primary hyperhidrosis. The subjects were divided into four groups depending on the technique used for sympathetic blockage; techniques included resection (n = 20), transection (n = 20), ablation (n = 20), and clipping (n = 20). The primary success rate was 96.3% for isolated palmar hyperhidrosis, 95.7% for palmar and axillary hyperhidrosis, and 66.7% for palmar and face/scalp hyperhidrosis. No recurrence was observed. The overall success rate of the operation was 95%, and the differences among the four groups were not statistically significant. In the clipping group, the duration of the surgical procedure was significantly shorter than in the other groups. Complication rates were similar among the groups. The postoperative chest roentgenogram revealed pneumothorax in 9 patients, but none of them required intervention. The authors concluded that thoracic endoscopic sympathetic blockage yields similar resultsirrespective of the surgical technique adopted, conclusions need to be tempered by the size of the study groups. In conclusion, future clinical trials comparing surgical techniques will need to ensure that the procedures are standardized and outcome measures validated for both symptoms of the disease and surgical complications. Finally, the studies must have large numbers of patients and adequate long-term follow-up, if they are to detect differences in results among procedures with very high technical success rates.
A single-center, randomized, open-label, study funded by Allergan (39) was conducted to compare the efficacy and safety of intradermal injections of botulinum toxin type A (BTX-A, Botox®) and 20% aluminum chloride (AC, Drysol™) topical for the treatment of primary focal axillary hyperhidrosis from baseline to week 4. Subjects (n =50) were men (n =14) and women (n =36) 18 years of age and older (mean age 29.9 years) who were randomized to either BTX-A or AC treatment. Prior to enrollment, more than 90% of the subjects in the study had used over-the-counter antiperspirants and described them as “poor” or “ineffective.” There was no significant difference in Hyperhidrosis Disease Severity Scale (HDSS) score at baseline. The primary endpoint was to determine the incidence of treatment response, as measured by an improvement of 2 or more grades on the HDSS. Participants returned for outpatient follow-up visits at weeks 4, 8, and 12 for an assessment of adverse events, changes in concomitant medications, and to complete two validated questionnaires HDSS, Hyperhidrosis Impact Questionnaire (HHIQ), and questions about irritation (QI), a third questionnaire. Given the very high dropout rate after week 4, the results are summarized here only for week 4 of treatment. Of the 50 subjects enrolled, 45 completed 4 weeks of the study, 22 from the BTX-A group and 23 from the AC group. The subjects in the BTX-A group had a mean change in their HDSS score of -2.42 versus -1.33 in the AC group. The difference in treatment response between the BTX-A and AC groups was not significant. On satisfaction with treatment at week 4, 21 subjects (87.5%) in the BTX-A group described themselves as “very satisfied” as compared with 8 (33.3%) in the AC group. To date, this is the only study directly comparing BTX-A with 20% AC for the treatment of moderate to severe axillary hyperhidrosis. However, the conclusions the authors draw, which state that BTX-A is superior to AC treatment in patients, will need further investigation with larger, longer term, randomized, blinded studies to determine if BTX-A would be appropriate as a first-line therapy.
Preliminary studies of botulinum type B (BTX-B) (40) have demonstrated potential to ameliorate focal hyperhidrosis, however, evidence is insufficient to determine the impact on clinical outcomes.
MyoblocTM (botulinum toxin type B, Solstice Neuro) (41) has received FDA approved for the treatment of patients with cervical dystonia to reduce the severity of abnormal head position and neck pain associated with the condition.
Summary
In summary, the issues identified with the 2008 update remain outstanding, i.e., the data are limited with respect to candidate suitability, treatment dosages, and frequency and duration of treatment. Future clinical trials will likely continue to compare surgical techniques. For such comparisons, procedures must be standardized and outcome measures validated for both symptoms of the disease and surgical complications. Finally, the studies must have large numbers of patients and adequate long-term follow-up, if they are to detect differences in results among procedures with very high technical success rates, and include head-to-head comparisons with other treatment options.
The policy statement regarding the use of intradermal injections of botulinum toxin type A for secondary gustatory hyperhidrosis, plantar, and craniofacial hyperhidrosis has been clarified as investigational, given the insufficient evidence available to evaluate the net health outcomes in comparison with alternative therapies. The policy statement has been modified to include botulinum type B for the treatment as investigational due to insufficient evidence to evaluate the net health outcome of this treatment. Lumbar sympathectomy has been added as an investigational indication due to lack of data/studies and concerns about side effects.
Physician Specialty Society Guidelines and Position Statements
American Academy of Neurology Assessment: Botulinum neurotoxin in the treatment of autonomic disorders and pain (an evidence-based review): report of the Therapeutics and Technology Assessment Subcommittee; May 2008. (35) The conclusions are discussed above.
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; August 2007. (42)
Multi-Specialty Working Group on the Recognition, Diagnosis and Treatment of Primary Focal Hyperhidrosis: In 2004, a multidisciplinary task force of internationally recognized experts released this consensus statement and recommendations. (26)
References:
- U.S. Food and Drug Administration. Early communication about ongoing safety review Botox and Botox Cosmetic (botulinum toxin type A) and Myobloc (botulinum type B). February 2008. Available online at: http://www.fda.gov/cder/drug/early_comm/botulinium_toxins.htm. Last accessed January 2009.
- 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.
- 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.
- Levit F. Treatment of hyperhidrosis by tap water iontophoresis. Cutis 1980; 26(2):192-4.
- 2003 TEC Assessment. Iontophoresis for Medical Indications.
- Goldman A, Wollina U. Subdermal Nd-YAG laser for axillary hyperhidrosis. Dermatol Surg 2008; 34(6):756-62.
- Allergan, Inc. Botox® (botulinum toxin type A) product information. Irvine, CA; October 2006. Available online at: http://www.allergan.com/assets/pdf/botox_pi.pdf. Last accessed January 2009.
- 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.
- 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.
- Shelley WB, Talanin NY, Shelley ED. Botulinum toxin therapy for palmar hyperhidrosis. J Am Acad Dermatol 1998; 38(2 pt 1):227-9.
- Naumann M, Hofmann U, Bergmann I et al. Focal hyperhidrosis: effective treatment with intracutaneous botulinum toxin. Arch Dermatol 1998; 134(3):301-4.
- 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.
- 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
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- 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.
- 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.
- 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.
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Codes |
Number |
Description |
CPT |
32664 |
Thoracoscopy, surgical; with thoracic sympathectomy |
|
64650 |
Chemodenervation of eccrine glands; both axillae (new code effective 1/1/06) |
|
64653 |
other area(s) (e.g., scalp, face, neck), per day (new code effective 1/1/06) |
| 69676 | Tympanix neurectomy | |
ICD-9 Diagnosis |
780.8 |
Hyperhidrosis |
| HCPCS | J0585 | Botulinum toxin, type A, per unit |
|
J0587 |
Botulinum toxin, type B, per 100 units |
Type of Service |
Medicine, surgery |
|
Place of Service |
Inpatient (thoracoscopic sympathectomy) |
|
Index
Botulinum Toxin, as Treatment of Hyperhidrosis
Endoscopic Sympathectomy
Gustatory Hyperhidrosis
Hyperhidrosis
Iontophoresis, as Treatment of Hyperhidrosis
Sweating, Excessive
Sympathectomy, Thoracic
Thoracoscopic Sympathectomy
Policy History
| Date | Action | Reason |
| 7/16/99 | Add to Therapy section | New policy |
| 7/12/02 | Replace policy | Policy reviewed without literature review; new review date only |
| 04/29/03 | Replace policy | Policy revised regarding iontophoresis as a treatment for hyperhidrosis based on 2003 TEC Assessment; policy statement revised to indicate that this is considered investigational (previously considered medically necessary) |
| 12/17/03 | Replace policy | Policy revised regarding surgical treatments of axillary hyperhidrosis; surgical excision considered medically necessary, axillary liposuction considered investigational |
| 02/25/04 | Replace policy | Correction in policy statement to remove surgical excision of axillary sweat glands from investigational statement in policy section |
| 11/9/04 | Replace policy | Policy updated with literature search; references added. Policy statement unchanged. No scheduled review |
| 12/14/05 | Replace policy – code update only | CPT coding updated. |
| 02/14/08 | Replace policy | Policy returned to active review and updated with literature search; reference 1, 2, 29 and 30 added; references renumbered; policy statements unchanged |
| 04/24/09 | Replace policy | Policy updated with literature search through December 2008, reference numbers 1, 6, 7, 34-40 added and renumbered. Policy statements changed to reflect the types of primary focal hyperhidrosis; axillary, palmar, plantar, and craniofacial. Policy statements revised as follows: botulinum type A medically necessary for severe primary axillary and palmar hyperdrosis; policy statement added for botulinum type A as investigational for plantar and craniofacial hyperhidrosis therapies; botulinum type B was added as investigational for all hyperhidrosis; lumbar sympathectomy was added as investigational for treatment of plantar hyperhidrosis; the policy statement regarding use of botulinum type A for secondary gustatory hyperhidrosis was changed to investigational |
| 08/13/09 | Replace policy | Policy updated with information about tympanic neurectomy, reference numbers 36 and 37 added and renumbered. Policy updated with information about FDA approved revisions to prescribing information for botulinum toxin products that included drug name changes; policy statements unchanged. |
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