Special Topic

Hyperhidrosis: A Review of CurrentManagementJoanne L. Atkins, M.B.Ch.B., M.Sc., F.R.C.S.(Eng.), and Peter E. M. Butler, F.R.C.S.I., F.R.C.S.(Eng.),F.R.C.S.(Plast.)London, United Kingdom

Primary hyperhidrosis is a troublesome disorder of ex-cessive perspiration that affects as much as 1 percent of thepopulation. Sufferers are usually young and are oftenaffected by related social, professional, and psychologicalproblems. Many methods for treating hyperhidrosis exist;however, no single treatment is without its weakness orcomplications. This article aims to clarify the issues relatedto the use of each treatment modality, including the mostrecently proposed method using botulinum toxin. (Plast.Reconstr. Surg. 110: 222, 2002.)

Hyperhidrosis is a pathologic conditioncharacterized by the secretion of sweat in ex-cess to the normal physiologic needs of thebody. Patients seeking medical help often findtheir work and social lives disrupted by profusesweating, commonly affecting the axilla, palmsof the hand, or soles of the feet. Psychosocialdifficulties, physical discomfort, and functionaldisruption are all problems experienced by thisgroup of patients. Damp hands may be misin-terpreted as a sign of anxiety, and damp axillaesoaking through clothes are a cause of acutepersonal embarrassment. Patients may feelphysical discomfort related to sodden shoesand clothing, and experience difficulties inperforming simple tasks at work, such as han-dling paper or ink, or gripping work tools.

Hyperhidrosis can be classified as a primaryor secondary disease. Primary hyperhidrosis isa disorder of unknown cause and may affect upto 1 percent of the population, although theprecise incidence is unknown. The conditioncommonly manifests in young adults; however,it may present as early as childhood and persistthroughout adult life.1,2 Secondary hyperhidro-sis can arise as a consequence of a number ofmedical conditions. The long list of possible

causes includes endocrine disease (hypoglyce-mia, hyperthyroidism), neurologic disorders(syringomyelia, focal lesions of the central ner-vous system), drug use (antidepressants, anti-emetics), the menopause, neoplastic disease(Hodgkin lymphoma, carcinoid tumors, pheo-chromocytoma), and chronic infection (TableI).3,4 Every effort should be made to identifyand correct any underlying cause before imple-menting a treatment plan.

PATHOPHYSIOLOGY OF PERSPIRATION

Human skin contains two functionally dis-tinct types of sweat gland, the eccrine and apo-crine glands.

Eccrine Glands

Eccrine glands account for the majority ofsweat glands and number approximately 3 mil-lion; they produce a thin secretion, hypotonicto plasma, which gives rise to hyperhidrosis ifsecreted in excess. Eccrine glands are skin ap-pendages that are embryonically derived fromthe surface epithelium. Each gland consists ofa simple coiled secretory portion located deepwithin the dermis, surrounded by a rich capil-lary plexus, and supplied by sympathetic post-ganglionic cholinergic fibers. A long straightduct leads upward from the body of the gland,through the epidermis, eventually openingonto the skin surface.

Eccrine glands are distributed throughoutthe skin in a common anatomic pattern. Den-sity of distribution varies, depending on theanatomic area, with the greatest density ofglands found in the axilla, palm, and sole ofthe foot.

From the Department of Plastic Surgery, Royal Free Hospital. Received for publication July 5, 2001.

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The primary function of sweat secretion isconcerned with thermoregulation; however,other accessory functions include maintenanceof the health and texture of the skin, withmoisture lending traction to the skin surface, auseful function when turning paper or grip-ping smooth objects. The regulation of the rateand volume of sweat production is normallycontrolled by the hypothalamus; sensory infor-mation related to the core body temperature isintegrated and assessed, and measures to in-crease or decrease the body temperature areinitiated. An increase in body temperatureleads to changes in both behavior and physiol-ogy aimed at temperature reduction. Heat lossthrough conduction is achieved by the diver-sion of blood flow to superficial vessels,whereas an increased rate of eccrine sweat se-cretion leads to heat loss from the skin surfaceby evaporation. The sympathetic signal leadingto this increase in sweat secretion is carried tothe eccrine glands through postganglioniccholinergic fibers. The rate of secretion is alsoincreased at times of emotional or physicalstress. In primary hyperhidrosis, affected indi-viduals appear to have a raised basal level ofsweat secretion and an exaggerated responseto the other normal stimuli mentioned.

Apocrine Glands

Apocrine sweat glands are less numerousthan eccrine glands and are localized to theaxillae and urogenital regions. They becomeactive at puberty and produce a viscid secretionunder the control of adrenergic nerve fibers;bacterial breakdown of these secretions by skincommensals produces an unpleasant odor.These secretions do not contribute tohyperhidrosis.

MANAGEMENT OPTIONS

The treatment of patients with primary hy-perhidrosis is not straightforward. Conservativetherapy with the use of topical agents may beunsuccessful and may lead to surgical referral.Surgical interventions using gland excision, li-posuction, or sympathectomy have associatedcomplications that may be unacceptable forthe treatment of a benign condition. Botuli-num toxin has recently been introduced intothe repertoire of existing treatments and canprovide a suitable alternative to existing thera-pies in some circumstances.

The aim of treatment of primary hyperhidro-sis is to reduce the volume of sweat secreted toa level that is acceptable to the patient. It isimportant to understand the motivation andexpectations of the patient before embarkingon a treatment plan, with appropriate patientcounseling for the potential complications andlimitations of any treatment. The treatmentoptions available can be considered as conser-vative or surgical (Fig. 1).

Conservative Treatment

There is a definite role for conservative ther-apy in the treatment of hyperhidrosis, with agood proportion of patients responding ade-quately to the current treatments availablewithout recourse to surgery. Although thesetreatments do not offer a permanent solutionto excessive sweating, they often produce ac-ceptable results with minimal morbidity.

Topical agents. Several topical agents havebeen used as treatment options for hyperhidro-sis. Agents applied to the skin achieve theireffect either by blocking the excretory ducts ofthe eccrine glands or are astringent, acting onthe sweat glands and the epithelium. A com-monly used effective antiperspirant is a satu-rated solution of aluminum chloride hexahy-drate in absolute alcohol. It can be a usefulagent in the control of local hyperhidrosis af-fecting the palms, soles, and axillae, and excel-lent results have been reported.5,6 Drawbacks tothis treatment include its short-lived effect, withcontinued success depending on daily applica-tion. Skin irritation is a potential complicationof treatment, occurring most frequently in theaxillary area, and may be intolerable to somepatients. In addition, application of topical so-lutions can be messy and time consuming, andover prolonged periods of use these difficultiesmay lead to reduced patient compliance. More-

TABLE ICauses of Hyperhidrosis

PrimaryIdiopathic

SecondaryPhysiological

(i.e., emotion, menopause, hot environment, exercise)Endocrine and metabolic

(i.e., thyrotoxicosis, diabetes mellitus)Drugs and substance abuse

(i.e., antiemetics, fluoxetine, narcotic withdrawal)Neoplasia

(i.e., Hodgkin disease, intrathoracic neoplasms,pheochromocytoma, central nervous system lesions)

Cardiovascular and respiratory disordersFebrile illness

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over, a small but significant group of hyper-hidrotic patients remain unresponsive to thistherapy.7

Astringent topical agents that are less com-monly used to treat hyperhidrosis include tan-nic acid and glutaraldehyde. Although theymay successfully control sweating, their ten-dency to stain the skin renders them generallyunacceptable to the patient.8

Systemic agents. Anticholinergic agents, suchas glycopyrronium bromide and propanthelinebromide, appear to be a logical choice to sys-temically decrease the secretion of sweat; how-ever, a number of unpleasant systemic side ef-fects limit their usefulness in clinical practice.Common side effects of these drugs include adry mouth, blurred vision, urinary retention,and constipation, and generally exclude long-term use.9

Benzodiazepines may be useful in decreas-ing anxiety and reducing the emotional stimu-lus to excessive perspiration in some patients.These agents may be useful only if taken forbrief periods, for example, before an antici-pated stressful situation, as long-term use canlead to dependency. Many patients find theeffects of lethargy and drowsiness associatedwith this group of drugs unacceptable.7

Iontophoresis. Iontophoresis has been de-fined as the introduction of an ionized sub-stance through intact skin by the application ofdirect current. It is a process that can be usedwith considerable success to treat localized ar-

eas of hyperhidrosis.2 The precise mechanismof action is not fully understood; however, it hasbeen suggested it may cause a temporary block-age of the sweat duct at the level of the stratumcorneum. A current of 15 to 30 mA can besupplied by a galvanic generator and deliveredto the affected area of the body by electrode.8The affected limb, with electrode attached, iseither placed in a shallow water bath (usingsimple tap water), or for other areas such as theaxilla, with a moistened cotton wool pad overthe electrode.5

Good results are achievable, especially forthe treatment of the palm and plantar areas,but the treatment is less successful for the ax-illa. The process needs to be repeated a vari-able number of times to obtain the desiredeffect, and maintenance therapy is required. Astudy of 30 patients required a mean average of15 treatments to achieve euhidrosis.10 Durationof euhidrosis can vary from 2 to 14 monthsafter cessation of treatment.

Complications of treatment are generallymild and may include erythema of the treatedskin, transient vesicular rash, and transient par-esthesia.2 Contraindications to treatment in-clude the presence of cardiac pacemakers,pregnancy, or metal orthopedic implants. Con-veniently, the treatment is easy to perform, isgenerally well tolerated, and the patient canbe trained to carry it out at home using theirown equipment.

FIG. 1. Summary of conservative and surgical treatment options forhyperhidrosis.

224 PLASTIC AND RECONSTRUCTIVE SURGERY, July 2002

Botulinum toxin. Botulinum toxin is a pow-erful neurotoxin produced by Clostridium botu-linum. It is currently used to treat a variety ofconditions including focal dystonias such asblepharospasm and spasmodic torticollis, andfor aesthetic improvement, in particular for thecorrection of brow-frown lines and periorbitalwrinkling.11 Its use as a successful treatment forlocalized gustatory sweating in Frey syndromehas also been reported.12

Botulinum toxin is a zinc-dependent endo-protease that is able to block neurotransmis-sion. It produces this effect through cleavageof the components of the cellular apparatusresponsible for the exocytosis of neurotrans-mitters. In the treatment of hyperhidrosis, bot-ulinum toxin blocks the release of the neuro-transmitter acetylcholine, therefore preventingsynaptic transmission and producing an effec-tive chemodenervation of the gland and a tem-porary cessation of sweating.13 It is particularlyuseful in the treatment of focal areas ofhyperhidrosis.

Application of the toxin involves multipleinjections to the affected hyperhidrotic area.The area can be identified with greater preci-sion by use of the iodine-starch test. Injectionsare spaced 1 to 2.5 cm apart, with injectiondose varying between botulinum toxin prod-ucts. Currently, botulinum toxin serotype A isthe most commonly used. For an axilla orpalm, approximately 50 units of toxin are re-quired to achieve an adequate effect.4,14 Fol-low-up suggests a quantitative reduction ofsweating of between 70 and 80 percent for theaxilla and a 26 to 31 percent reduction aftertreatment of the palms.4,15

The duration of the therapeutic effect ofbotulinum toxin varies depending on each in-dividual and the dose given, with a return ofsweating reported after a gap of between 3 and8 months.14 Reports of continued adequatecontrol of sweating at 1-year follow-up havebeen reported using a higher dose, with 500units of botulinum toxin being injected intoeach axilla.16

Complications of treatment are generally mi-nor and transient. These include hematoma atthe site of injection and paresthesia; however,weakness of the small muscles of the hand canbe a problem in the treatment of palmar hy-perhidrosis, leading to a reduced force of grip.This may be a more important issue in somepatients more than others and should be em-phasized during consent for treatment. Anti-

body formation against the toxin remains apossibility and may lead to reduced therapeuticeffectiveness.

The major drawback to this treatment is thediscomfort associated with the mode of appli-cation in the form of multiple injections. Thisis particularly problematic in the treatment ofthe palms of the hand and soles of the feet;pain from injection to these sensitive areas mayprove to be intolerable to the patient and un-acceptable to the surgeon. Application of atopical local anesthetic cream to the injectionsite before treatment may help in some cases,as may regional nerve block. Unlike the palmand sole, injections to the axilla appear to bevery well tolerated, and hyperhidrosis of thisarea may be a primary indication for the use ofbotulinum toxin.

Surgical Treatment

Surgery remains a valuable option for thetreatment of some cases of hyperhidrosis. Be-cause of a number of potential complications,its use should be reserved for only the moreaggressive forms of the disease that remainunresponsive to conservative therapy.

Excision of axillary tissue. Several surgicalmethods involving excision of axillary tissue canbe used to manage hyperhidrosis of the axilla.Three basic types of procedures are described.These include the excision of subcutaneous tis-sue alone, removal of skin and underlying sub-cutaneous tissue en bloc, or skin excision withexcision of underlying subcutaneous tissue andexcision of adjacent subcutaneous tissue.

Breach advocated the first category of proce-dures that involves the placement of three par-allel transverse incisions 1.5 cm in lengthacross the axilla. Through these incisions, theunderlying skin of the hyperhidrotic area isundermined and subcutaneous fat is removedin the same fashion as for a full-thickness graft.Of 25 patients (50 axillae) treated with thisapproach, 23 reported minimal or no sweatingat 1 year and were subjectively pleased with theresult. The remaining two patients were satis-fied with the reduction in sweating and did notrequire a further procedure.17 Other surgeonsusing similar techniques for axillary osmidrosishave found that 79 to 92 percent of patientsnoted a marked decrease in the volume ofsweat produced at long-term follow-up. Thereported complication rate appears to be low(4 to 6 percent).18,19

In 1963, Hurley and Shelley described a sim-

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ple technique whereby an ellipse of skin wasexcised from the dome of the axilla and sub-cutaneous tissue approximately 0.5 cm deep isremoved en bloc. The resulting defect is closeddirectly. Although this simple technique pro-duced favorable results in reducing perspira-tion, subsequent problems associated withtightness of the axillary fossa from scarring andreduced volume of skin detract from this tech-nique. Modifications of the technique usingZ-plasty or a lazy-S incision may alleviatethese problems.

An alternative technique involves removing asmall area of affected skin and subcutaneoustissue en bloc, as well as the removal of subcu-taneous tissue alone in the adjacent area.20 Thearea affected by sweating is marked out usingthe iodine starch test. A central S shape of skinand underlying tissue is excised as well as thesubcutaneous tissue underlying the entirety ofthe marked area. Design and closure of theflaps as an S avoids the tension of a straight linethat is produced using an elliptical excision;excision of the surrounding subcutaneous tis-sue allows for a more extensive procedure.

Use of the iodine-starch test as originallydescribed by Weaver allows accurate placing ofskin incisions over the affected area, therebyincluding the majority of eccrine glands andimproving the likelihood of a satisfactory out-come.21,22 Complications associated with surgi-cal removal of skin or subcutaneous tissue fromthe axilla include wound infection, slow heal-ing, skin edge necrosis, wound hematoma,wound dehiscence, hidradenitis, and axillaryhair loss. Scarring can lead to reduced mobilityof the shoulder, and incisions and skin closureshould be carefully planned.

Axillary liposuction. A technique for subder-mal axillary liposuction has been described, car-rying out suction via an incision in the anterioraxillary fold. The entire subdermal surface canbe treated with the cannula holes directed to-ward the dermis.23 A similar technique has beenused for the treatment of axillary osmidrosis,with reports of a reduction in sweat volume aswell as odor.24 The success of the technique maypartly be because of disruption of the nervesupply to the sweat glands and removal or de-struction of the apocrine glands that arepresent in the axilla in high density. Liposuc-tion techniques are not yet widely used to treathyperhidrosis; therefore, the true efficacy ofthis treatment is unknown.

Thoracoscopic sympathectomy. Sympathetic fi-bers supplying the eccrine glands of the palmand axilla arise from the T2 to T4 ganglions ofthe upper dorsal sympathetic chain, respec-tively. Interruption of the thoracic sympatheticchain is a well-documented method of treatingpalmar hyperhidrosis, and to a lesser extentaxillary hyperhidrosis.25 Interruption of thesympathetic chain leads to permanent cessationof sweating within the nerve distribution. His-torically, open procedures were performed togain access to the thoracic sympathetic chains.These procedures carried a high rate of mor-bidity, and in recent years have been replacedby minimal-access techniques.

Thoracoscopic interruption of the sympa-thetic chain requires general anesthesia butcan be performed as a short-stay procedure insuitably healthy patients. Patients can usuallyreturn to normal activity within a few days afterthe operation. Contraindications to treatmentinclude respiratory impairment and pleural ad-hesions. Access to the thoracic cavity is usuallygained through the third intercostal space inthe anterior axillary line after the collapse ofthe ipsilateral lung.26 The second, third, andfourth thoracic ganglia are identified and maybe ligated with clips before division, althoughelectrocautery may be used as an alternative.1

In experienced hands, success rates of 87 to98 percent have been reported for palmar-axillary hyperhidrosis, although treatment foraxillary hyperhidrosis alone has been less suc-cessful.25 The condition may recur if the chainis incompletely divided, anatomic landmarksare incorrectly identified, or nerve regenera-tion occurs.

Iatrogenic complications that may arise fromthe procedure can be serious and include Hor-ner syndrome (transient or permanent), pneu-mothorax, thoracic duct injury, hemothorax,phrenic nerve damage, and death.27 Side ef-fects of the sympathectomy itself include com-pensatory sweating, which the patient may finddistressing. This can affect as many as 50 per-cent of patients, being more common in pa-tients with bilateral procedures, and often in-volves excessive sweating on the trunk, limbs,or face. Gustatory sweating has also been re-ported following sympathectomy, affecting asmany as one-third of patients.28 In patients re-ceiving treatment for palmar hyperhidrosis, itmay be wise to treat only the dominant handinvolved to reduce the risk of developing com-pensatory sweating. Permanent nonfunction of

226 PLASTIC AND RECONSTRUCTIVE SURGERY, July 2002

the eccrine glands following sympathectomymay lead to hyperkeratosis, scaling, and fissur-ing of the skin; this may be distressing for thepatient and difficult to treat.7

Lumbar sympathectomy for the treatment ofpedal hyperhidrosis has been described but isnot generally used. In men and women, a com-plication of the technique may cause sexualdysfunction because of ensuing impotence andanorgasmia.

CONCLUSIONS

Individuals affected by hyperhidrosis incurunpleasant physical and psychological effectsstemming from the volume of sweat produced.The majority of patients presenting for treat-ment of this condition complain of symptomsrelated mainly to the upper limb, and manyhave suffered for several years before seekinghelp. Although many treatment modalities ex-ist, the success of the treatment used varies,depending in part on the area of the bodyaffected and the severity of the problem.

The ideal treatment of choice should be suc-cessful, safe, and inexpensive. Conservativetreatment should be tried before progressingto the more permanent and usually irreversibleeffects of surgery. Botulinum toxin is a rela-tively new treatment and provides good resultsin achieving euhidrosis over a prolonged pe-riod of time. It is particularly useful in thetreatment of axillary hyperhidrosis and willprobably replace tissue excision or sympathec-tomy as a treatment for aggressive axillary hy-perhidrosis. Focal areas of hyperhidrosis, suchas that seen in Frey syndrome, are also easilyand adequately treated by botulinum toxin.

Thoracic sympathectomy has a high successrate in achieving relief from hyperhidrosis ofthe palm alone or in combined disease with theaxilla; results are not as satisfactory for treat-ment of the axilla alone. The serious potential

complications associated with the proceduremust be taken into account; however, for pa-tients with disease affecting the axilla andpalm, or palm alone, thoracic sympathectomyremains the surgical treatment of choice (Ta-ble II).

Peter E. M. Butler, F.R.C.S.I., F.R.C.S.(Eng.),F.R.C.S.(Plast.)

Department of Plastic SurgeryRoyal Free HospitalPond StreetHampsteadLondon NW3 2QGUnited Kingdompembutler@hotmail.com

REFERENCES

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2. Stolman, L. P. Treatment of excess sweating of thepalms by iontophoresis. Arch. Dermatol. 123: 893, 1987.

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5. Simpson, N. Treating hyperhidrosis. Br. Med. J. 296:1345, 1988.

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8. Moran, K. T., and Brady, M. P. Surgical management ofprimary hyperhidrosis. Br. J. Surg. 78: 279, 1991.

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TABLE IIPrimary Hyperhidrosis: Treatment Options and

Anatomic Areas

Method Area

Conservative treatmentTopical agents Palmar, pedal, axillaIontophoresis Palmar, pedal, axillaBotulinum toxin Axilla, focal disease

Surgical treatmentThoracic sympathectomy Palmar, palmar-axillary diseaseTissue excision AxillaLiposuction Axilla

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17. Breach, N. M. Axillary hyperhidrosis: Surgical cure withaesthetic scars. Ann. R. Coll. Surg. Engl. 61: 295, 1979.

18. Tung, T. C., and Wei, F. C. Excision of subcutaneoustissue for the treatment of axillary osmidrosis. Br. J.Plast. Surg. 50: 61, 1997.

19. Wang, H. J., Cheng, T. Y., and Chen, T. M. Surgicalmanagement of axillary bromidrosis: A modified sk-oog procedure by an axillary bipedicle flap approach.Plast. Reconstr. Surg. 98: 524, 1996.

20. Bisbal, J., del Cacho, C., and Casalots, J. Surgical treat-ment of axillary hyperhidrosis. Ann. Plast. Surg. 18:429, 1987.

21. Weaver, P. C. Axillary hyperhidrosis. Br. Med. J. 1: 48,1970.

22. Davis, P. K. B. Surgical treatment of axillary hyperhi-drosis. Br. J. Plast. Surg. 24: 99, 1971.

23. Shenaq, S. M., and Spira, M. Treatment of bilateral

axillary hyperhidrosis by suction assisted lipolysis tech-nique. Ann. Plast. Surg. 19: 548, 1987.

24. Ou, L. F., Yan, R. S., Chen, I. C., and Tang, Y. W. Treat-ment of axillary bromhidrosis with superficial liposuc-tion. Plast. Reconstr. Surg. 102: 1469, 1998.

25. Chaudhuri, N., Birdi, I., and Ritchie, A. J. Current prac-tice in thoracic sympathectomy. Hosp. Med. 60: 807,1999.

26. Malone, P. S., Cameron, A. E. P., and Rennie, J. A. Thesurgical treatment of upper limb hyperhidrosis. Br. J.Dermatol. 115: 81, 1986.

27. Greenhalgh, R. M., Rosengarten, D. S., and Martin, P.Role of sympathectomy for hyperhidrosis. Br. Med. J.1: 332, 1971.

28. Andrews, B. T., and Rennie, J. A. Predicting changes inthe distribution of sweating following thoracoscopicsympathectomy. Br. J. Surg. 84: 1702, 1997.

228 PLASTIC AND RECONSTRUCTIVE SURGERY, July 2002