Introduction

Hyperhidrosis (HH) is an excessive sweating disorder that affects 2.8% of the population in the United States alone. By definition, HH is sweating beyond what is expected for environmental conditions and thermoregulation. In practice, it is considered sweating that significantly interferes with daily life. Not only does it cause anxiety and emotional distress for those who suffer from it, but it can also be a risk factor for cutaneous infection, eczematous dermatitis, and muscle cramps. Lear et al reported that most patients who have HH experience it in areas of high eccrine density such as the axillae (51%), soles (30%), palms (24%), and occasionally in the craniofacial area (10%). Multiple modalities are available for treatment of primary focal HH, from topical medications such as aluminum chloride, to non-surgical approaches such as iontophoresis and botulinum toxin injections, to systemic medications such as clonidine and even surgical sympathectomy. In this chapter, we will discuss the role of botulinum toxin in the treatment of HH of the palms and soles.

Patient evaluation

Most patients who present with palmar HH have had the condition since childhood or early adolescence with no known cause and report ‘sweaty palms’ that cause them social embarrassment. Solish & Haider reported evidence suggesting that an autosomal dominant inheritance pattern with variable expressivity such that a child born to a parent with palmar HH has a 25% chance of developing the disorder as well. Patients will go to great lengths to avoid shaking people’s hands and often keep their hands in their pockets. The hyperhidrosis can be so severe as to cause actual physical dripping and maceration and peeling of the skin itself (Fig. 24.1). Similarly, patients with plantar hyperhidrosis will report the need to change socks frequently or that they ‘slip’ in their shoes while walking. Interestingly, a study by Lear and colleagues suggested that spontaneous regression might occur over time as there is a low prevalence of the disorder in the elderly population. It is important for the physician to keep in mind the severe psychological impact HH has on patients, many of whom do not seek treatment due to embarrassment and yet decrease their leisure activities and suffer from depression because of it.

Figure 24.1 Severe palmar hyperhidrosis.

Prior to treatment, it is important to take a careful clinical history to ensure that the patient suffers from primary, not secondary, hyperhidrosis. In secondary hyperhidrosis, medications or systemic health problems can be responsible for sweating (Box 24.1) and the condition is usually generalized. If there is a suspicion of secondary hyperhidrosis, a complete blood count, fasting glucose level and thyroid function test are preliminary laboratory tests to be ordered.

In primary hyperhidrosis, neither the number, density, nor size of eccrine glands is abnormal; rather there is overactivity of the postganglionic sympathetic cholinergic fibers innervating them. For this reason, botulinum toxin type A can be effective in treatment; the toxin inhibits presynaptic release of acetylcholine and binds to acetylcholine receptors at the postsynaptic membrane thus disrupting sympathetic input to eccrine glands. Because eccrine glands are found in a high concentration in the axillae, palms, soles, and forehead, these are the areas where primary focal HH typically presents as excessive sweating for at least 6 months’ duration. To make a positive diagnosis of focal primary HH, Hornberger stated that the patient should also present with at least two of the following criteria: age at onset younger than 25 years, frequency of at least one episode per week, a positive family history, cessation of sweating upon sleep, impairment of activities of daily living, and a distribution that is bilateral and relatively symmetric. Of note, Hamm et al found that palmar hyperhidrosis can present unilaterally in 6% of cases.

Scoring the impact of hyperhidrosis on the patient’s quality of life is important as well, not only to gauge treatment success but also to aide in obtaining insurance approval for treatment. The Hyperhidrosis Disease Severity Scale (HDSS) is a quick diagnostic tool that the practitioner can administer during the examination and was found by Solish and colleagues to be a reliable means of assessment (Table 24.1). HDSS scores should be followed to guide the choice of treatment and to determine whether treatment has made an impact (success should be considered a reduction in HDSS of 1 or more).

Table 24.1 Hyperhidrosis disease severity scale

General considerations

Treatment of palms and soles for primary focal HH is considered an off-label use of neurotoxin. In the United States, botulinum toxin type A (which is FDA approved for treatment of axillary HH) is commercially available as Botox^® (Allergan, Irvine, CA, USA), Dysport^® (Medicis, Scottsdale, AZ, USA), and Xeomin^® (Merz Pharmaceuticals, Greenboro, NC, USA). All are considered pregnancy category C and it is advisable to avoid injection in actively nursing women. All patients should be screened for allergy to botulinum toxin type A components and injections should not be placed into areas that appear infected or inflamed. It is important to be aware of the patient’s current medication list as certain medications can alter the metabolism of neurotoxin such as aminoglycoside antibacterials, cholinesterase inhibitors, and calcium channel antagonists.

Walling & Swick considered that botulinum toxin injections for palmar HH should be reserved for patients who have first failed treatment with topical aluminum chloride and oral glycopyrrolate at a concentration of 1–2 mg up to three times a day. These authors then suggested trying iontophoresis and, if that fails, subsequently using neurotoxin injection.

Marking the treatment areas

The Minor’s iodine-starch test can be used to estimate the areas of involvement that require treatment but should not be relied upon for precise quantitative measure of sweating. In brief, the palms or soles are first wiped with iodine (pre-packaged swabs of povidone-iodine are particularly useful for this) and allowed to dry. Next, the painted area is sprinkled with cornstarch powder. A colorimetric reaction ensues, resulting in a bluish-purple discoloration in areas of excess sweating that can then be marked for injection (Fig. 24.2). To ensure accuracy, patients should discontinue any topical therapies 5 days prior to iodine-starch testing. While this test is advocated for the axillae, we feel it is less helpful for the hands as the test usually demonstrates a positive reaction over the entire palm. For most patients, we advocated marking in a grid-like pattern with the iodine-starch test first (Fig. 24.3).

Figure 24.2 Colorimetric reaction, showing the bluish-purple discoloration in areas of excess sweating. Starch iodine test showing significant improvement of palmar hyperhidrosis after injection with botulinum toxin A.

Figure 24.3 Marking the palm in a grid-like pattern with the iodine-starch test marking the palm prior to injection with botulinum toxin A. Injections should be made beside the ink to avoid potential tattooing.

Anesthesia

Pain is a common complaint when performing injections for the palms and soles. For this reason, different techniques to lessen the pain may be employed. Ice cubes held with gauze (or frozen with gauze on the outside) can be held on the skin for approximately 10 seconds prior to injection. This can dramatically decrease the discomfort associated with the injection. The ice is then moved to the next location while the injection is taking place. Ice is preferred over freezer packs, as ice will maintain its temperature. Skin-cooling devices, such as those made by Zimmer, can also work effectively at decreasing pain prior to injection.

Another alternative to ice and cooling devices is the use of nerve blocks. For the palms, median and ulnar nerve blocks are required. For the median nerve block, locate the palmaris longus tendon and inject 2 mL of 1% lidocaine into the radial side at the proximal wrist crease. For the ulnar nerve block, identify the flexor carpi ulnaris tendon and inject just radial to it on the proximal wrist crease at the ulnar styloid process.

For plantar injections, both a sural nerve and a posterior tibial nerve block are needed. A sural nerve block will anesthetize the fifth toe and lateral side of the sole. It requires injection of 3–5 mL of 1% lidocaine between the lateral malleolus and the Achilles tendon. A posterior tibial nerve block anesthetizes the heel and middle of the sole of the foot. For this nerve block, palpate the posterior tibial artery near the medial malleolus. The nerve is lateral to the artery. Inject 5 mL of 1% lidocaine in the groove between the medial malleolus and the Achilles tendon. Wait 15 minutes for regional nerve blocks to take full effect.

Despite above, some patients continue to experience pain. In that case, we advise the use of high-intensity vibration devices (e.g. AcuVibe^®) adjacent to each injection site to overstimulate nerve fibers and lessen the pain. It should be noted that reactive hyperemia might follow regional nerve blockade to the wrists, increasing the tendency of the skin to bleed at each injection site.

Dilution and injection

Though many dilution techniques exist, we find that for palmar and plantar injections, dilution of one vial of Botox^® with 3 mL of bacteriostatic preserved saline results in a manageable concentration for injection (Table 24.2). With the 3 mL dilution, each 0.1 mL results in 3.3 U of Botox^®. To prevent unnecessary waste of the toxin, we recommend removal of the lid and rubber stopper on the bottle vial so that no product is left behind, and use of hubless syringes. Since palmar and plantar skin is thick, needles dull more quickly after serial injection. Therefore, it is best to draw up the 100 U into six 0.5 mL syringes (B&D Ultra-Fine II 30-gauge hubless insulin needle syringes, Becton-Dickinson). Volumes of 0.05–0.1 mL (1.7–3.3 U) of Botox^® should be deposited at each injection point spaced 1–1.5 cm apart because less diffusion occurs on the palms and soles compared with other body sites.

Table 24.2 Acceptable dilutions for botulinum toxin type A in the treatment of palmo-plantar hyperhidrosis

For severe palmar hyperhidrosis, Dysport^® has also shown efficacy; using a conversion factor of 1 : 4, Simonetta et al demonstrated that Dysport^®-treated palms actually retained anhidrosis for a similar period of time to those treated with Botox^®. Though the decrease in sweat was more pronounced in the Dysport^®-treated palms, this finding did not reach statistical significance. Local side effects were more frequent in Dysport^® palms than in those treated with Botox^® and manifested as a decrease in thumb-index pinch for up to 30 days, compared with up to 21 with Botox^®. If using Dysport^® for hyperhidrosis, we recommend dilution with 3 mL of bacteriostatic preserved saline, which gives a final dilution of 10 U per 0.1 mL. Unlike Botox^® vials, the top and rubber stopper do not need to be removed from the Dysport^® vial as an insulin syringe can easily penetrate the top without dulling of the needle.

Injection technique

Proper injection depth for the palms and soles is at the junction of the dermis and subcutaneous tissue (the location of the eccrine glands). The needle should be inserted at an oblique angle and product placed into the deep dermis. Superficial injection decreases the probability that the neurotoxin will diffuse into the intrinsic muscles of the hands and cause weakness (Fig. 24.4). It is common to see a small zone of blanching around each injection point on the palms and soles; the wheal produced during neurotoxin injection in other parts of the body such as the axillae and forehead is not seen when performing palmar and plantar injections. Approximately 50–100 U of Botox is standard dosing for each palm depending on the size of the area; 100 U of Botox is reasonable to use per sole owing to the larger surface area. Though some authors recommend a range from 100 to 240 U of Botox per hand, one randomized, single-blind trial by Saadia and colleagues showed similar efficacy between 50 and 100 U of botulinum toxin type A for palmar HH. Of note, the higher dose was associated with an increased incidence of subjective hand weakness. For this reason, we recommend starting with 50 U per hand then reassessing the first-time patient at 1 month. Injections typically need to be repeated every 6 months.

Figure 24.4 Superficial injection.

Results and follow-up

Several studies have measured efficacy of botulinum toxin type A both quantitatively and subjectively in palmar HH and they report 80–90% improvement with anhidrosis lasting anywhere from 4 to 12 months (see Grunfeld et al). Most patients will relate some degree of hand weakness 24–72 hours after injection that can persist for up to 2 weeks. Handgrip strength is usually retained whereas thumb–index finger pinch strength is weakened. For patients who are in professions that require fine hand movement and strength, we recommend treating one hand and then the other at a later visit after discussion with the patient. After injection, pain and soreness are common and can last up to 2 days. In addition, mild numbness, paresthesias, and small hematomas at the injection sites can occur (though uncommonly and are transient).

Follow-up is recommended every 5 months in treatment-naïve patients and every 6–7 months in patients treated on a regular basis. After treatment, it is reasonable to counsel patients that they will begin to notice a difference in 7–10 days. Bleeding is common at the time of injection so it is advisable to ask an assistant to hold pressure with gauze in the areas that have already been treated.

Compared with palmar HH, plantar HH is more difficult to ameliorate. Treatment efficacy tends to be lower in the soles than in the hands or axillae and usually higher doses of botulinum toxin type A are required. Few randomized, controlled trials exist to assess the true efficacy of neurotoxin injection into the feet. Although we have observed a decrease in plantar HH after neurotoxin use to treat palmar HH, recent evidence suggests that no difference is detected.

Complications

The most common side effect from injection of the palms is bruising and mild discomfort immediately after treatment. Persistent superficial injections can lead to weakness of the muscles of the hand and over time may lead to atrophy. Palmar injections can be complicated by adverse events related to regional nerve blocks such as inadvertent vascular puncture, impaired hand dexterity, and neuropathy from repeated nerve injuries, as reported by Fujita and colleagues and Hayton et al.

Plantar injections are usually painful and include adverse side effects of both pain and hematomas at injection sites. If regional nerve blocks are used, the patient will have difficulty walking for several hours and it is recommended that they not attempt to drive for 4–5 hours after the procedure.

Conclusion

Palmar and plantar hyperhidrosis can have severe psychological impact on those who suffer from the disease. Often topical medications such as aluminum chloride and oral medications such as glycopyrrolate are inadequate to treat the symptoms. In these cases, botulinum toxin type A injection provides a method for producing anhidrosis. Though more effective for the palms than for the soles, the technique for injection is easy to use and reliable. For both of these sites, the greatest challenge for the physician is maintaining adequate pain control for the patient. Often after the first successful treatment, however, patients with severe disease become quite motivated and are able to handle the pain with more ease than the physician may expect.