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Narrative Review

Hyperhidrosis of the residual limb: a narrative review of the measurement and treatment of excess perspiration affecting individuals with amputation

Lannan, Ford M.1; Powell, Jordan2,3; Kim, Gabriel M.2,3; Hansen, Colby R4; Pasquina, Paul F.2,3; Smith, Douglas G.2,3,5

Author Information
Prosthetics and Orthotics International: December 2021 - Volume 45 - Issue 6 - p 477-486
doi: 10.1097/PXR.0000000000000040

Abstract

Background

Individuals with acquired limb loss encounter numerous physical, mental, and emotional challenges that affect their quality of life.1 Successful use of a prosthesis has a major impact on the quality of life for a person with an amputation.1,2 Poor skin health of the residual limb is associated with reduced performance and less time spent in the prosthesis.3 Prevalence of residual limb skin problems has been reported between 15% and 73% for prosthesis users.4,5 Furthermore, skin problems for individuals with acquired limb loss may persist for many years after their amputation. For example, Yang et al6 reported that 48.2% of Vietnam veterans with amputation reported skin disease in the preceding year, up to 38 years after amputation.

Excess perspiration is generally considered a significant contributor to problems with skin health and poor fit and function.7-10 Hyperhidrosis (HH), or excessive sweating, was the single most reported skin issue in a survey of people with lower-limb amputation.11 Specifically, excess perspiration can lead to foul odors and residual limb skin pathology such as maceration, dermatitis, fungal infection, ulceration, and verrucous hyperplasia.12 More than 53% of individuals with amputation experience discomfort associated with heat and/or perspiration from their prosthesis.13 In addition to discomfort and skin disease, excessive sweat can accumulate inside the liner, causing the liner to slip and compromise the suspension of the prostheses, altering gait and potentially leading to prosthesis dysfunction and falls.14

Despite the advent and use of advanced prosthetic materials over the past 2 decades, excessive perspiration of the residual limb remains a significant challenge for prosthesis users.15 Unfortunately, there is also a lack of evidence-based guidelines for the assessment and treatment of hyperhidrosis in a person with amputation. Moreover, despite the high prevalence and impact of excessive sweating in individuals with acquired limb loss, there is no literature that specifically defines hyperhidrosis or subjectively and objectively characterizes the problem. The purpose of this review was to appraise the current state of both quantitative and qualitative assessment of HH within the residual limb and examine the existing and future treatment strategies for this problem.

Methods

A review was conducted of the existing literature regarding the assessment and treatment of HH in residual limbs. Although the overall search was comprehensive, the focus of this study was a narrative vs. systematic review of the literature because of the fact that other than the use of botulinum toxin (BTX), there is a relative dearth of primary research studies involving the assessment and treatment of hyperhidrosis of residual limbs to systematically compare. Searches were conducted from database inception through March 2020. The literature search was conducted in relevant textbooks and in four online databases, PubMed, Medline, Embase, and Web of Science, to find relevant articles pertaining to the topic. Keywords such as “hyperhidrosis,” “residual limb,” “amputation,” “sweat,” “perspiration,” “liner,” “prosthetic,” and “socket” were used in our search. References found within the relevant articles were also used to expand the search further. Eligibility criteria included English-language papers related to the above keywords. The emphasis of the search was to include all studies involving persons with amputation; however, additional articles were included if they contained relevant information on focal primary hyperhidrosis in patients without amputation. Exclusion criteria included animal studies and publication before 1980. Three authors (F.L./J.P./G.K.) screened the titles and abstracts against inclusion/exclusion criteria.

Discussion

Pathophysiology of sweating within a prosthesis

Sweating in humans occurs through eccrine and apocrine glands. Apocrine sweat glands are mainly located in the axillae and anogenital region and do not exist in significant numbers on residual limbs.16 Eccrine glands are located over most of the body with the exceptions of the external ear canals, lips, and labia minora. They function by receiving signals from the sympathetic nervous system that has acetylcholine rather than norepinephrine as the terminal neurotransmitter. On receiving this signal, the glands, which are located in the lower dermis, secrete a dilute solution that mainly consists of sodium chloride to the surface of the skin through a duct that travels directly from the secretory coils of the gland (Figure 1). Eccrine glands are the main sweat gland in humans responsible for thermoregulation.17 Evaporative cooling from sweating is one of the main systems for heat dissipation besides heat exchange by convection through cutaneous vasodilation and, specific to persons with amputation, heat conduction from the skin to prosthetic components.18,19

F1
Figure 1.:
Eccrine sweat gland in normal skin and a nearby hair follicle.

Although generalized sweating is controlled by internal body temperature by central mechanisms, an increase in focal sweat rate is influenced by local temperatures of the eccrine gland by an intrinsic process.17 Thereby, focal residual limb sweating in individuals with acquired limb loss is typically a primary problem and not a secondary process related to a systemic disorder or to any functional abnormality of the glands themselves.16 Although in people without amputation, the disorder mainly affects the palms, soles of feet, or axilla, the interface between the socket and the skin is the site most commonly affected in individuals with acquired limb loss. In people without an amputation, HH seems to be most often caused by an amplified central response to normal stress.16 By contrast, excess perspiration in individuals with amputation most likely stems from a combination of the occlusive nature of the prosthetic liner and relatively excessive perspiration from the residual limb because of increased temperature within the microenvironment of the socket.14

A large percentage of persons with lower-limb amputation suffer from diabetes.20 For hyperhidrosis of the residual limb, current literature is lacking as to whether there are significant differences between traumatic amputations and those related to diabetes. Although diabetes is commonly cited as a condition that contributes to secondary HH, some literature suggests that distally, persons with diabetes actually sweat less than controls.21-23

Approach to diagnosis

Because hyperhidrosis of the residual limb has not been formally defined, at this time, it is solely a clinical diagnosis. In the authors' practice, excessive sweating (focal, visible sweating on the residual limb) that affects the fit and/or function of the prosthesis is defined as hyperhidrosis. With that said, the subjective individual disability caused by excess sweating, while not specifically studied in the literature, is likely variable.

On presentation to the clinic, patients with amputation often report excess perspiration or have skin pathology associated with a reaction to the chronically moist environment on the residual limb.13,24 Examples of common dermatoses associated with and exacerbated by the occlusion of residual limb skin within the socket include folliculitis, miliaria rubra (prickly heat), eczema, irritant or allergic contact dermatitis, cellulitis, or dermatophytosis (fungal infections).5 Patients may also report frequently having to change their liner during activity because of excess perspiration. Other patients will present with findings that are indirectly the result of excess perspiration such as impaired fit or loss of suction, which can lead to complaints of decreased stamina with the prosthesis or, in the worst-case scenario, overt falls.25,26

Assessment methods for residual limb hyperhidrosis

There are currently no studies formally detailing what objectively or subjectively constitutes HH of a residual limb. Clearly defined qualitative and quantitative assessment methods for HH of the residual limb are needed to aid in diagnosis.

Quantitative methods for assessing hyperhidrosis

The methods used for objective assessment of sweat production include gravimetry, vapometry, and, less commonly, skin resistance. Gravimetry is the measure of sweat per unit time. Sweat is collected on the patient's area of concern over the course of 1 minute and then weighed. Stefaniak and Proczko27 used a large cohort to obtain mean gravimetric values for different body sites that were normalized with each subject's body surface area. Using normal distribution theory, they standardized the hyperhidrosis threshold as the mean plus two SDs for each site. Reported cutoff values for the axilla and the plantar surface of the feet were 136 and 50 mg·min·m2, respectively. No such standardized values exist for HH in the residual limb. Of interest, Stefaniak et al28 also found significant discordance between subjective HH assessment of individuals without amputations and their above results of objective gravimetric test cutoff values. Although similar research has not been performed in people with limb loss, it would not be surprising if a similar discordance between quantitative gravimetric data and subjective HH assessment exists among individuals with amputations.

Vapometry measures the gas output of the skin using transepidermal water loss (TEWL), which can be used as a quantitative measure of sweating. Traditionally, TEWL values are affected by the state and function of the stratum corneum and there is evidence that increased TEWL is associated with skin barrier dysfunction.29 For this reason, any measure of perspiration using vapometry should be conducted on skin without evidence of pathology, such as a hypertrophic scar or healing wound.30 A validated and practical device used for measuring TEWL is the VapoMeter (Delfin Technologies Ltd, Kuopio, Finland).29-31 The VapoMeter can be successfully used on small surface areas and is ideally suited for use on a person's residual limb (Figure 2). As briefly described, the device chamber is placed against the skin for approximately 10 seconds and the instrument reports the TEWL in g·m2·hr. In HH patients who underwent suction-assisted arthroscopic shaving of the sweat glands as treatment for primary axillary HH, vapometry was shown to produce accurate and reproducible measures of the relative humidity in the axilla.32 To the best of our knowledge, there is currently no literature that defines residual limb cutoff values for HH based on vapometry.

F2
Figure 2.:
Measurement of transepidermal water loss on a lower extremity residual limb using the VapoMeter.

A less commonly used technique for quantification of sweating is the measurement of skin resistance. Theoretically, skin with increased perspiration is more electrically conductive and therefore has a lower resistance. Misiak et al33 found that measuring skin resistance with a universal multimeter (Metex Me-31; Metex Corporation, Seoul, South Korea) was effective in showing decreased perspiration in response to thoracic sympathectomy in primary HH of people without amputation. However, one study evaluating palmar hyperhidrosis found vapometric differences but not skin conductance differences between patients and controls,34 and thus, its usefulness in diagnosing HH requires further research.

Although a quantitative approach to assessing severity of sweating is not necessary for routine clinical practice, future research should focus on correlating quantitative perspiration measurements with subjective assessment of hyperhidrosis and prosthesis fit and function. It is important to note that all of these methods would be difficult to perform inside a prosthetic liner and socket during real-time functional activity. However, an asynchronous standard set of cutoff values at rest and shortly after activity could help to diagnose HH of a residual limb. If cutoff values for HH became better understood or standardized, perhaps quantitative assessment of HH would be clinically viable. Even if these quantitative methods are of limited diagnostic value, they still may play a role in assessing and monitoring the response to treatment.

Qualitative methods for assessing hyperhidrosis

Because quantitative assessment of perspiration may not always correlate with symptomatology,28 qualitative assessment methods can be a valuable tool in the assessment of HH. The current qualitative assessment tools for assessing focal HH in individuals without amputation include the Hyperhidrosis Disease Severity Score (HDSS) (Table 1), the Hyperhidrosis Impact Questionnaire, and the Dermatology Life Quality Index.35 Much of the research to date on residual limb HH has used the HDSS and custom questionnaires.13

Table 1. - The Hyperhidrosis Disease Severity Scale.
“How would you rate the severity of your hyperhidrosis?” Score
1. My sweating is never noticeable and never interferes with my daily activities 1
2. My sweating is tolerable but sometimes interferes with my daily activities 2
3. My sweating is barely tolerable and frequently interferes with my daily activities 3
4. My sweating is intolerable and always interferes with my daily activities 4

The HDSS is a brief single-item scale and requires no specialized tools to perform. Multiple studies have analyzed the validity and reliability of the HDSS and found it to correlate well with the Hyperhidrosis Impact Questionnaire and Dermatology Life Quality Index, as well as objective measures of sweating in people without amputation.36,37 Generally, a 1-point improvement in the HDSS correlates with a 50% reduction in sweat production and a 2-point improvement correlates with an 80% reduction in sweat production.38 The same reduction is yet to be validated or explored in the population of individuals with limb loss. A recent study in people with amputation found a strong correlation between the HDSS and sweating interfering with prosthetic function or fit using a 5-point Likert scale.39

Minor's starch-iodine test is commonly used to identify focal areas of HH.40,41 Of note, this test has been shown not to quantify the degree of sweating as compared with other methods such as gravimetry, but can be used to map the area of excess sweating before initiating local treatments with BTX or surgery.41,42 It is our clinical experience that performing the starch-iodine test requires donning the prosthesis to produce a reliable sweat reaction from which to plan local treatments. To this end, Hansen et al43 explored different ways of administering the starch-iodine test and concluded that covering the limb with a prosthetic sheath and prosthesis and then having the patient ambulate for 10 minutes produced focal or multifocal reactions in 100% of patients and were well-tolerated. Color change from light brown to dark purple indicates an area of perspiration because the iodine and starch form a complex in the liquid medium of eccrine sweat.44 Much of the starch-iodine stain transfers to the sheath, so the stain pattern on the sheath can be used to identify hyperhidrotic areas on the residual limb (Figure 3).41

F3
Figure 3.:
Results of the starch-iodine test after 10 minutes of ambulation. Left. The sheath has been set next to the residual limb as if it were a mirror image to illustrate the areas of sweat reaction—in this case, along the anterior supra- and infrapatellar regions. Right. Subsequent marks identifying the region of interest for applying botulinum toxin in 1–2 cm intervals. Images courtesy of Dr. Hansen.

Future research should strive to standardize qualitative assessment methodology for HH of the residual limb. In contrast to qualitative instruments for HH, there are more than 50 qualitative instruments to measure function in people with amputation; however, there is no consensus about which is most appropriate to assess prosthetic function in the setting of HH.45

As a standardized approach, this group recommends that researchers begin using the HDSS (Table 1) in addition to a reliable and valid prosthetic function and quality-of-life instrument, such as the Prosthesis Evaluation Questionnaire.46 The Prosthesis Evaluation Questionnaire can be self-administered and specifically addresses functional and mobility issues indirectly affected by HH.46 When coupled together with the HDSS, these data could be used to normalize and validate quantitative values such as from vapometry associated with symptomatic HH of the residual limb. If standardized, this would allow future researchers to report the prevalence of HH on residual limbs with improved external validity and reliability and potentially guide treatment based on the severity of symptoms.

Treatment for residual limb hyperhidrosis

Established treatment algorithms for HH may not always translate to persons with acquired limb amputation. Treating HH of the residual limb is often complicated by other residual limb problems, including residual limb pain, folliculitis, neuromas, poor soft tissue coverage, skin breakdown, heterotopic bone formation, complex and hypertrophic scars, and/or verrucous hyperplasia.14 Initial management should be conservative. The clinician should ensure that the individual with an amputation has a well-fitting socket with an appropriate liner, including the provision of an additional liner to allow patients to exchange liners throughout the day and especially during prolonged physical activity. Patients should be advised to regularly doff the prosthesis and remove pooling sweat from the socket as well as dry the moisture on the interface and skin. In addition, a moisture-control prosthetic sock may be used in combination with the liner. Finally, topical hypoallergenic antiperspirants are generally a safe and reasonable first-line approach.38

Role of prosthetic components

The occlusion created by a typical prosthetic–human interface plays a key role in both the pathogenesis and treatment failure of residual limb HH.14,47 Components of the prosthetic interface may include a variety of liners, socks, and thermoplastic or laminated sockets. There are several ways to optimize the prosthetic–liner interface to reduce heat retention and the effects of moisture, which should be considered when selecting components of the interface.

Prosthetic sock considerations

Prosthetic socks and sheaths can be made from various combinations of materials including cotton, wool, nylon, polyester, elastane, and acrylic. The goals of a prosthetic sock are to reduce shear forces on the skin, accommodate fluctuations in residual limb volume, and provide shock absorption. Although these are often placed over a liner, they are also frequently used underneath the liner in an attempt to decrease the consequences of perspiration by absorption and wicking.48,49 Various prosthetic socks have been marketed as moisture wicking or absorbent;50,51 however, no studies exist that have directly examined these properties. Hansen et al39 found that among surveyed individuals with amputation, the use of a sock or sheath had mixed perceptions of effectiveness, but did trend toward being more effective than topical antiperspirants.

Prosthetic liner considerations

A liner is an elastomer or foam interface worn between the residual limb and the socket. It helps to protect the soft tissue from shear, pressure, and trauma while improving residual limb fit of the socket.18 The material composition, thickness, and fit of the liner can affect residual limb temperature and the effects of sweat. However, this must be balanced with other factors when choosing a liner, including the need to reduce skin shear forces, offload bony prominences, control pistoning, or account for redundant soft tissue. Klute et al52 studied the thermal conductivity of different liner materials and found that silicone-based liners had the highest thermal conductivity, meaning that they allow more heat to be transferred from the warm residual limb to the cooler exterior environment. Closed cell foam–based liners, such as Pelite, had lower thermal conductivity, with mineral oil derivative liners (thermoplastic elastomer) being in the middle.52 Liner material and thickness were reported as being able to change the residual limb temperature several degrees.52 Cagle et al53 subsequently investigated liner thermal conductivity and also included polyurethane liners, which were found to have similar thermal conductivity to silicone. Regarding retention of perspiration, Hachisuka et al10 demonstrated that moisture permeability across silicone and polyethylene liners was more than 80 times less compared with having no barrier. Wernke et al54 reported that incorporating phase change material into their liners helped reduce postactivity skin temperature and perspiration. Phase change material acts to increase the heat capacity of the liner, thereby absorbing more thermal energy from the residual limb, while becoming softer or “changing phase” as the heat is transferred and stored in the liner.54

There is an active effort to make innovative liners that can reduce perspiration. Sleeman et al developed a silicone liner with embedded coolant tubes connected to a pump, which circulates cold water, and was able to achieve a sustained limb temperature drop.55,56 Dolomisiewicz et al57 investigated elastane-based hybrid suspension liners with moisture-wicking capability that subjectively decreased warmth and moisture when used with thermoplastic or carbon fiber sockets in short transfemoral and hip disarticulation patients. Finally, Caldwell and Fatone47 described a technique for creating dozens of tiny perforations to silicone liners, which resulted in some expulsion of sweat, and patients reported anecdotal improvement in HH symptoms. Overall, these results suggest that (1) a silicone or polyurethane liner would perform the best at dispersing heat when compared with other liners and (2) there is minimal moisture permeability across both silicone and polyethylene liners.

Socket considerations

Although the liner is essentially water-impermeable, perspiration can drip down from the proximal end of the liner and into the socket, which can potentially affect the seal in a suction socket. A commonly used solution is wearing an absorbent sweat band just above the liner to prevent perspiration from dripping down. Changing between thermoplastic and carbon fiber sockets is unlikely to change limb temperature or perspiration because the thermal conductivities of both thermoplastic and carbon fibers are very similar.52 Nurhanisah et al58 studied the effects of several different socket fenestration patterns on limb temperature in a single patient, with only the most fenestrated pattern showing a very modest reduction in limb temperature. However, fenestration of socket walls may reduce socket stability and increase sheer stress.59

New and emerging socket technologies are being developed, which may help with perspiration and temperature control. A battery-powered cooling fan within the socket and a phase change heat sink have been proposed, for which two patents exist.60-62 The use of nanomaterials with high thermal conductivity within the structure of the socket has also been proposed.63 Ghoseiri et al64 created a prototype socket with a thermoregulatory system incorporating heat sensors, a thermal pump, and aluminum structure within the socket to transmit heat. Webber and Davis65 constructed a socket with a helical cooling channel embedded in the socket to draw heat away from the limb. Klute et al66 designed a socket that uses a pump to cause dynamic air exchange from the distal and proximal ends of the socket to expel perspiration from within the socket and cool the limb. Although active cooling systems are not commercially accessible at this time because of constraints of cost, weight, and power source requirements, perforated liners and Phase Change Material liners are available.

Pharmacological interventions

Topical medications

Topical aluminum ion–based antiperspirants (i.e., aluminum chloride, aluminum zirconium, and aluminum hydroxy bromide) have been a mainstay in treating excess sweating of residual limbs. These compounds act to stop perspiration by clogging the sweat ducts.67 Often, these are the first-line therapy used by prosthetists to decrease excessive perspiration; however, they require reapplication, often result in skin irritation, and are at times not well-tolerated.14 Application of the topical at night to dry skin while not wearing the prosthesis (e.g. before bed) will decrease irritation. Washing the limb in the morning, after application at night, will wash away any residue from the delivery agent but will leave the aluminum ion below the surface of the skin in the sweat ducts, reducing the chance of skin irritation. Dilution of prescription strength solution may also decrease irritation.68 Emollients are commonly used on residual limbs to reduce skin irritation and friction, and some have been marketed as reducing the effects of sweating by sealing moisture within the skin.49 However, some liner manufacturers caution that petroleum and lanolin, ingredients found in several brands of emollients, may accelerate deterioration of the liner.69 Moreover, it is important to note that lanolin can cause allergic contact dermatitis.

A newer topical agent is Qbrexza, a glycopyrrolate impregnated cloth that is administered by wiping the targeted skin. It is currently indicated to treat axillary HH.70 It has not been studied in patients with amputation. Theoretical concerns may exist of systemic toxicity if used over a large surface area and on an occlusive environment such as created by a residual limb covered by liner/socket material.70

Oral medications

Anticholinergic medications such as glycopyrrolates at a dose of 1–2 mg two to three times daily are used as a systemic medication to decrease sweat production. They work as a competitive antagonist of acetylcholine receptors, which innervate eccrine sweat glands. Unfortunately, these medications as a class are not specific to sweat glands and cause typical antimuscarinic side effects such as dry mouth (most common) and tachycardia, urinary retention, and constipation.71 Pace and Kentosh noted in their practice that although many individuals with limb loss tolerated the glycopyrrolate and reported decreased sweating overall, the incidence of skin pathology on the residual limb did not decrease proportionally.14 This suggests that the side effects of the anticholinergics prevent a high enough dose to be administered to decrease sweating sufficiently to overcome the occlusive environment of the prosthetic socket. This also suggests that in order for a treatment for residual limb HH to be maximally effective, it must eliminate sweating in the focal area of the residual limb. Other oral therapies used for HH include beta-blockers, benzodiazepines, and alpha-2 adrenergic agonists.72 There are no data available as to their use in individuals with amputation. Limited data available in the general population suggest that they may have some effect on anxiety-driven or generalized HH.72

Injectable medications

Botulinum toxin injection is considered first- or second-line treatment for axillary, palmar, and plantar HH.68 Two preparations of BTX-A serotype are used to treat HH in the United States: onabotulinumtoxinA (Botox) and abobotulinumtoxinA (Dysport).73,74 The BTX-B serotype, available as rimabotulinumtoxinB (Myobloc) in the United States, is also used for HH to a lesser degree. Many studies, mostly case reports or small case series, have shown efficacy of BTX in treatment of HH in individuals with amputation (Table 2).75-81 Most studies used the starch–iodine test to identify injection sites, whereas other studies identified other types of injection techniques. Charrow et al76 managed to improve residual limb sweating and use of the prosthesis in eight people with amputation by administering a dose of 300–500 Units of BTX-A in a circumferential pattern at 1 cm intervals. Kern et al77 performed injections of BTX-B 2–4 cm apart with a statistically significant anhidrotic effect in nine individuals with limb loss during an uncontrolled pilot study. During a randomized placebo-controlled study by Pasquina et al,75 participants received intradermal injections of either BTX-B or placebo. Each injection was evenly spaced every 4–6 cm2 in a grid pattern covering the surface area of the participant's residual limb that is normally in contact with their prosthetic socket. The mean sweat reduction for the BTX-B group by gravimetric analysis was 72.7% ± 15.7%, statistically higher than the mean reduction of 32.7% ± 39.2% in the placebo group (P < 0.05).

Table 2. - Summary of effects of botulinum toxin.
Reference Dose Toxin type Dilution ratio No. of patients Injection technique Conclusion
Charrow et al76 300–500 units in 2–3 unit aliquots (400 units transtibial, 400–500 units transfemoral, and 300 units transradial/humeral) OnabotulinumtoxinA (Botox) 100 units/mL 8 Circumferential pattern at 1 cm intervals Anhidrotic effect lasted 3 weeks
Gratrix and Hivnor25 300 units in 1.25 unit aliquots (transfemoral) OnabotulinumtoxinA (Botox) 25 units/mL 1 Starch–iodine test Anhidrotic effect lasted at least 3 months
García-Morales et al80 300 units in 2 unit aliquots (transtibial) OnabotulinumtoxinA (Botox) 20 units/mL 1 Starch–iodine test Anhidrotic effect lasted 3 months
Wollina et al79 100 units in 1.25–2.5 unit aliquots (transtibial) OnabotulinumtoxinA (Botox) 25 units/mL 1 Starch–iodine test Anhidrotic effect lasted 3 months
Kern et al77 1750 units (transfemoral and transtibial) RimabotulinumtoxinB (Myobloc) 1750 units/mL 9 20 injection sites 2–4 cm apart Significant anhidrotic effect and a significant improvement in use of the prosthetic device, duration of use, and quality of life evaluated after 4 weeks and 3 months
Pasquina et al75 10,000 units (transtibial)
20,000 units (transfemoral)
RimabotulinumtoxinB (Myobloc) 2500 units/mL 9 Undisclosed number of injection sites 4–6 cm2 apart Significant anhidrotic effect in treatment group compared with placebo group at 4–6 weeks. Both groups reported a significant reduction in sweat interference with prosthetic function evaluated after 4–6 weeks
Adapted with permission from tables by Lezanski-Guida et al.87

Despite the lack of high-quality studies of BTX use for residual limb HH, BTX is well-known to be safe.82 Kern et al77 noted that among nine people with limb loss who received BTX for HH, adverse events were infrequent and mild in nature. Incidence of autonomic adverse effects is reportedly higher with BTX-B than BTX-A,83 but this is probably at doses too high for HH treatment.84 New topical BTX preparations are being investigated, including transdermal drug delivery by jet nebulization and the noncovalent binding of the toxin to a proprietary peptide for intradermal transport.85,86

Given the seasonal nature of residual limb HH, our experience shows that many individuals with amputation do well with one to two treatments per year during the warmest part of the season. Based on the available literature, and consistent with other indications for which BTX is used, the duration of effect is approximately 3 months (Table 2). Additional studies with longer follow-up periods are warranted, however, to determine length of efficacy more precisely.

Botulinum toxin injection is ultimately a temporary solution as the toxin's effects on the eccrine glands are transient.87 Devices that destroy and/or injure eccrine glands through the use of energy should, theoretically, be more effective than the above treatments because eccrine glands have limited capacity for regeneration.88

Other modalities

Laser therapy

The purpose of laser therapy in the individual with acquired limb loss is 2-fold. First, hair destruction is achieved through targeting the melanin chromophore within hair follicles.89 Removal of excess hair in the interface between the skin and the prosthesis can increase skin integrity by limiting friction and reduce focal sweating by decreasing heat retention. Second, laser therapy is theorized to injure or destroy nearby eccrine sweat glands through thermal heating.90 An added benefit of laser hair removal comes from lessening the need for shaving, a perilous task associated with cuts, abrasions, and folliculitis. Neodymium:yttrium-aluminum-garnet and diode lasers have been used in both topical and subdermal approaches to treat axillary HH with mixed results.72 A study of 20 people with an amputation using a 755-nm long-pulsed Alexandrite laser on the residual limb, which also targets melanin, found that the Skindex-16 (a health-related quality-of-life survey to evaluate the impact of dermatological issues) scores improved.91 Of note, this study focused on the use of the laser as a hair removal device, but they also observed that subjective reporting of sweating improved dramatically with their treatments. This suggests that this modality may target both the pilosebaceous unit and the surrounding eccrine sweat glands. Moreover, the participants in the study reported zero complications from the procedure.91 However, more research specific to residual limb HH is needed to evaluate laser treatment efficacy and safety for HH. Specifically, studies on axillary HH using an external 1064-nm neodymium:yttrium-aluminum-garnet laser on hair reduction settings showed similar subjective reduction in sweating as the above study in individuals with limb loss, but histologic examination showed no change in sweat gland morphology or number, suggesting that sweat reduction would only be temporary.92

Microwave thermolysis

Microwave thermoablation by the miraDry device (miraDry Inc, Santa Clara, CA) has been approved by the Food and Drug Administration for the treatment of focal axillary HH. The device functions to generate heat by physical rotation of water molecules, thereby selectively targeting water-rich eccrine glands in the dermis, while simultaneously cooling the surface of the skin. The miraDry creates irreversible destruction of eccrine sweat glands, thus leading to a substantial decrease in sweat glands histologically.93 One study found an efficacy of 90% in people without amputation as measured by a decrease in HDSS scores by 2 or 3 points from baseline and a >50% reduction of sweat measured gravimetrically.93 A case report of an individual with acquired limb loss using microwave thermolysis on the residual limb reported subjective improvement in sweating and less slippage within the prosthesis.26 This resulted in greater stamina for the individual in the report, with only transient edema and erythema reported as side effects.26

Fractional microneedle radiofrequency

Fractional Microneedle Radiofrequency delivers thermal energy to the eccrine glands through fractional bipolar radiofrequency energy using insulated microneedle electrodes. In one study on axillary HH, the patients reported an average decrease in HDSS of 1–2 points.94 In addition, histologic analysis after treatment showed a reduction in the size and number of eccrine sweat glands.72 To date, Fractional Microneedle Radiofrequency has not been studied for residual limb hyperhidrosis.

High-intensity ultrasound

High-intensity focused ultrasound produces thermal lesions that cause damage at the level of eccrine sweat glands, thus working to decrease perspiration. Two devices have been studied in the setting of HH treatment, the Ulthera System (Ulthera Inc, Mesa AZ), which is noninvasive, and the VASER system (Solta medical, Bothell, WA), which is applied subdermally through an incision.72 The Ulthera system is unique in that therapeutic energy is delivered with visualization, which theoretically could enable the user to avoid heterogeneous anatomy present within the residual limb such as underlying heterotopic ossification. In one study with the Ulthera conducted in axillary HH, more than 80% of patients reported subjective improvement and long-lasting effects at 12 months post-treatment.88 To date, high-intensity ultrasound has not been studied for residual limb hyperhidrosis.

Iontophoresis

Iontophoresis treatment uses galvanic current transfer through skin immersed in a liquid medium, typically water.72 Several theories concerning the underlying mechanism of action exist.72 Iontophoresis, being an effective and first-line treatment for palmar and plantar HH, was reported to be less effective in patients with limb loss.14,95 Moreover, although there are several commercially available devices that use tap water, there are no devices on the market made specifically for residual limbs.96

Limitations

Although every effort was made to include pertinent studies, some relevant articles might have been missed by the above literature search. Otherwise, in an effort to balance a comprehensive review with a clinically relevant focus, a specific discussion about different amputation levels and the associated amount of sweating was omitted because it is our assertion that the approach to the patient, assessment, and overall treatment strategy is relatively similar regardless of the site. Moreover, we did not include a discussion about direct and indirect temperature monitoring of the residual limb or invasive surgical techniques to treat hyperhidrosis.

Conclusion

HH of the residual limb for individuals with acquired limb loss is exceedingly prevalent and may lead to significant skin problems, impaired prosthetic functioning, and poor quality of life. Clinicians should be aware of the underlying pathophysiology of HH, the quantitative and qualitative instruments to help aid in comprehensive assessment of patients with amputation, and a stepwise clinical treatment approach to guide effective treatment. Proper assessment and effective management to improve heat dissipation and reduce sweat production/accumulation are the mainstays of treatment to promote the preservation of residual limb health and the safe and comfortable use of prostheses. These interventions may have a dramatic effect on promoting social reintegration and reducing the negative psychological consequences often accompanying limb amputation.

Funding

The authors disclosed that they received no financial support for the research, authorship, and/or publication of this article.

Declaration of conflicting interest

The authors declared the following potential conflicts of interest for the research, authorship, and/or publication of this article: C. R. Hansen has an active grant from DoD to study hyperhidrosis in people with amputation. The remaining authors declare no conflict of interest for the research or publication of this article. The identification of specific products or scientific instrumentation is considered an integral part of the scientific endeavor and does not constitute endorsement or implied endorsement on the part of the author, DoD, or any component agency. The views expressed in this study are those of the author and do not reflect the official policy of the Department of Army/Navy/Air Force, Department of Defense, or U.S. Government.

Supplemental material

There is no supplemental material in this article.

Acknowledgments

The authors would like to acknowledge Matthew Coffman, MD, and Michael Corcoran, CPO, for fruitful discussions and suggestions for improvement of the manuscript.

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Keywords:

hyperhidrosis; amputation; residual limb; prosthetics; interdisciplinary rehabilitation

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