Revi ew Treatment (~{ palmoplantar hyperhidrosis Irea,tment q/palmoplanmr hyperhidrosis R.S. Altman and R.A. Schwartz SUMMARY Palmoplantar hyperhidrosis, excessive sweating from the palms and soles, is often an embarrassing and disabling condition that afflicts individuals of all ages. Diagnosis is usually evident based upon the history and visible signs of sweating. Treatment of this condition has proven to be difficult; however, numerous treatment options are now available. The therapeutic armamentarium includes topical and systemic agents, iontophoresis, botulinum toxin injections, and sympathectomy, all of which will be discussed. Introduction Hyperhidrosis, an excessive race of sweat secretion from the eccrine glands , is a disabling condition that affects both children and adults. With an incidence rate of 0.6 to 1% documented in the young Israeli popula- tion 1 and onset usually during childhood or adolescence, palmoplantar hyperhidrosis (excessive sweating ofthe palms and soles) bas been noted to occur twenty times more frequently in the Japanese than in any other eth- nic group. 2•3 Palmoplantar hyperhidrosis may frequently be observed in chronic alcohol abusers. 1 Unlike sweat- ing on the remainder of the body, palmoplantar hyper- hidrosis is induced by emotions , not thermoregulation. Hyperhidrosis of the palms and soles is remarkable in that it does not occur during sleep or sedation because the hypothalamic sweat control center receives input from the cerebral cortex. This varies from the ther- moregulato1y hypothalamic center controlling sweat- ing from the rest of the body. Individuals with hyper- hidrosis have morphologically and functionally normal eccrine glands however, their glands are hypersensi- tive to stimuli in the hypothalainic sweat centers.; Pa- tients with palmoplantar hyperhidrosis have hypotha- lamic sweat centers that are hypersensitive to emo- tional stimuli of cerebral origin. 6The number of eccrine sweat glands per individual varies from two to four mil- lion with the greatest density on the palms and soles.5 Diagnosis is evidenc by the histo1y and visible signs of sweating. Many patients complain of social embar- rassment and work-related disability due to palmoplantar hyperhidrosis . Unfortunately, this condi- tion has not been easy to treat. Fortunately, many treat- ment options, including topical and systemic agents, Acta Dermatoven APA Vol 11, 2002, No 1 - - ------ ------------ -- 21 Treatment of palmoplantar hyperhidrosis iontophoresis, botulinum toxin injections, and sympa- thectomy, are now available. Treatment Therapy can be challenging both for patient and physician. Fortunately, numerous medica!, surgical and electrical treatment options are now available. Treat- ment may require visualization of the affectecl area, which may be accomplished by the iocline starch test (spraying the area with a mixture of 0.5 to 1 gram of iodine crystals ancl 500 grams of soluble starch). The treatment options inclucle topical ancl systemic medi- cations, iontophoresis, injections ofbotulinum toxin, ancl sympathectomy: Numerous topical chemicals have been utilized in- clucling topical anticholinergics, boric acicl, 2-5 % tannic acicl solutions, resorcinol, potassium permanganate, formaldehyde, glutaraldehycle, ancl methenamine. Sen- sitization may result with formalclehycle use. 7 20 % alu- minum chloride hexahydrate in absolute anhydrous ethyl alcohol (Drysol®) has been consiclered to be the most effective topical agent. This procluct should be used nightly on cl1y skin with or without occlusion until a positive result is obtained, at which tirne the intervals may be lengthened. At morning, the remainder of the aluminum chloricle should be washed off and neutral- ized with an application oftopical baking soda powcler in order to minimize irritation.8 The mechanism of ac- tion of aluminum chloricle may be clue to a pora! ob- structive effect, thereby climinishing sweating, in addi- tion to atrophy of the secretory cells seen in eccrine sweat glands.6 Systemic anticholinergic agents including propan- theline bromide QJrobanthine®), glycopyrrolate (Robinu!®), oxybutynin (Ditropan®), and benztropine (Cogentin®) may be effective because, although the eccrine sweat glancls are innervated by the sympathetic nervous sys- tem, the periglanclular neurotransmitter is acetylcho- line. However, anticholinergics have a poor side effect profile (including myclriasis , bluny vision, d1y mouth and eyes, difficulty with micturition, and constipation) which renders their use unappealing to many sufferers of hyperhidrosis. Many individuals understandably do not want to use these agents on a Iong-term basis as is required. Other systemic medications that may be ben- eficial for patients with unwanted palm and sole sweat- ing include sedatives ancl tranquilizers, indomethacine9 , and calcium channel blockers (Diltiazem®) 10 • Calcium channel blockers have been found to be effective be- cause they block the essential primary step of calcium influx into the eccrine secreto1y celi, thereby prevent- ing the stimulato1y signal for the secretion of water ancl electrolytes from the secretory ce!I. 11 Most patients fine! both the to pica! and systemic agents ineffective in abol- ishing their hyperhiclrosis, leading them to search for other options. Iontophoresis, introducecl in 1952 12, is one of the most effective, safe ancl inexpensive treatment options available. I3•15 It consists of passing a direct current (DC) across the skin. A representative study showecl that in 25 patients with palmar hyperhidrosis, symptoms were abatecl after an average of 11 treatments (30 minutes per treatment at least four times per week) of either DC or AC/DC tap water iontophoresis. However, for undiscussecl reasons, alternating current (AC) ionto- phoresis was found to be essentially ineffective after 25 treatments. 16 55 % of these 25 patients noted a fam- ily history of palmar hyperhiclrosis.16 The side effects noted were burning and tingling of the treated area, irritation (erythema ancl vesicles), ancl the induction of possible burns at areas of minor skin injrny. 16 Numerous agents have been used in iontophoresis including tap water ancl anticholinergics. In order to incluce hypo- hydrosis, treatment of each palm or sole for 30 minutes at 15 to 20 milli-amperes (mA) daily in tap water ionto- phoresis is requi.red. 17 Intact skin can endure 0.2mA/cm2 of galvanic current without negative consequences and up to 20 to 25 mA per palm may be tolerated. 17 The mechanism of action of iontophoresis is unknown. One speculation was that iontophoresis incluced pora! hy- perkeratosis, thereby promoting pora! plugging ancl inhibition of sweat secretion. 18 However, no such pora! plugging was found. 19 Tap water iontophoresis is more effective than saline iontophoresis. 20 Iontophoresis with -anticholinergics is more effective than tap water ionto- phoresis, but may induce systemic side effects. 21 Palmo- plantar hyperhiclrosis may be effectively treatecl with 10 to 12 treatments (30 minutes at 15-20 mA at least three times per week) ancl one to two maintenance closes per week of tap water iontophoresis, with the only complication being mild skin irritation. 13 With the initial treatment, patients founcl worsening oftheir con- dition , but this resolvecl after three to five treatments. 13 Complete abolition of sweating was found to last one to two weeks ancl sweating quickly returned without main- tenance therapy. 13 A newer stucly incorporatecl both, anticholinergics and aluminum chloricle for one hour daily. It diminished the sweat secretion (via tl1e anti- cholinergic) ancl caused blockage of the sweat glancl (via the aluminum chloricle). 22 This combination iontoc phoresis treatment comparecl to tap water iontophore- sis resultecl in a remission period of 20 days versus 3.5 days and a recluction in severity of symptoms of -3.1 versus -1.5 . 22 A device for use at home (the Drionic®) is now available ancl makes this treatment option more accessible. Botulinum toxin injection is a newer therapeutic moclality. The mechanism of action is due to the anti- cholinergic effects at the neuromuscular junction ancl in the postganglionic sympathetic cholinergic innveration of the sweat glands.23 Four patients with severe hyper- Review 22 --- ------ ------------------- -------Acta Dermatoven APA Vol 11, 2002, No 1 Review hidrosis were treatecl with 50 subepidermal injections of 2 mouse units per palm (after receiving regional median and ulnar nerve blocks) resulting in anhidrosis that lasted from 4 to 12 months. 21 Each injection pro- cluced a 1.2 cm diameter of anhidrosis. The only side effect noted was mild transient thumb weakness in one of the patients that subsequently resolved in three weeks. A randomized clouble-blind study of 11 patients with palmar hyperhidrosis received 120 mU of botuli- num A toxin (6 sites) in one palm versus saline solution in the other palm which resulted in a mean reduction of sweat production in the palm treated with the toxin of 26 percent after three and eight weeks and 31 percent after 13 weeks. 25 The only side effects noted were a minor muscle weakness at the toxin treated sites in all ofthe patients , that resolvecl after two to five weeks, as well as minor hematomas at the injection sites in one pati en t. 25 These injections must be repeatecl at varying intervals in orcler for long-term results to be maintainecl. Sympathectomy involving the surgical destruction ofthe ganglia cont:ributing to the hyperhidrosis, has been used asa permanent but effective treatment option for hyperhidrosis since 1920, usually reservecl as the ulti- mate treatment moclality. 26 The second and thircl tho- racic ganglia are responsible for palmar hyperhiclrosis. This procedure is usually not carried out for plantar hy- perhidrosis due to the risk of sexual dysfunction. 6 Nu- merous complications plague this treatment option, including compensato1y sweating (incluction of sweat- ing in previously unaffectecl parts of the body), gusta- tory sweating, pneumothorax, intercostal neuralgia, Horner's synclrome, sequelae of general anesthesia ancl return of the hyperhiclrosis. The endoscopic thoracic approach has recently been favored over the traditional open approach due to reduced complications and cli- minished surgical times and scars. Of 47 patients af- flicted with palmar hyperhidrosis treated with an out- patient thoracoscopic limitecl sympathectomy via elec- trocaute1y, there were no recurrences after 12.8 months, l> r;, rp ,:;, l) J? i~ r ,r, ji' S . l .!i.,;;.i. · .i .. , .1 .. _,.1 \- t., ... ,t., Treatment of" palmoplantar hyperhidrosis and mild compensatory sweating was reportecl in 74.5 percents with no incidences of Horner's syndrome. 27 Of 850 patients treated with bilateral endoscopic tran- sthoracic sympathectomy, 98% were pleased with the results 31 months post-surgery. 28 The complications noted were hemothorax/ pneumothorax in 1 %, treat- ment failures in 2%, and recurrence of symptoms in 2% of the patients. 28 Compensato1y sweating (mostly on the tnmk) occurred in 55% of those treated, with 2% of those affectecl stating that the compensatory sweating was comparably clistressing as was their initial hyper- hidrosis .28 In adclition, gustato1y sweating was notecl in 36%, and a 10% reduction in heart rate was founcl in 15% of the patients. In a similar stucly of 72 patients with palmar hyperhiclrosis treatecl with transthoracic endoscopic sympathectomy, a success rate of 93% was reported, with an alarming rate of compensato1y sweat- ing in 71 of the 72 patients (described as moderate in 41.7% and severe in 43.1 %), gustato1y sweating in 17%, Horner's synclrome in 7%, pneumothorax in 8%, ancl intercostals neuralgia in 7% of the patients .29 Despite the 93% success rate, only 77.7% of the patient'> were pleasecl w ith the results, clue to the side effects. 29 Treat- ment of the compensato1y sweating that results follow- ing transthoracic endoscopic sympathectomy can be effective with botulinum toxin intradermal injections.30 Conclusion Effective treatment modalities va1y from patient to patient requiring the physician to experiment with nu- merous options before finding the most efficacious choice. Suggested first line methods inclucle 20% alminium chloride hexahydrate in anhydrous ethyl al- cohol topically, ancl iontophoresis . Some prefer botuli- num injections. As a last resort for relief from hyper- hiclrosis, one may consider surgical sympathectomy. l. Adar R, Kurchin A, Zweig A, Moses M. Palmar hyperhidrosis and its surgical treatment: a report of 100 cases. Ann Surg 1977; 186:34-41. 2. Cloward RB. Treatment of hyperhidrosis palmaris (sweaty hands). A familial disease in Japanese .. Hawaii Med] 1957; 16:381-9. 3. Cloward RB. Hyperhidrosis. J Neurosurg 1969; 30:545-51. 4. Tugnoli V, Eleopra R, DeGrandis D. Hyperhidrosis and sympathetic skin response in chronic alco- holic patients. Clinical Autonomic Research 1999; 9:17-22. 5. Wenzel FG, Horn TD. Nonneoplastic disorders of the eccrine glands. J Am Acad Derrnatol 1998; 38:1 -17. 6. Stolman LP. Treatment of hyperhidrosis. Dennatologic Clinics 1998; 16:863-7. 7. Shelley \VB, Laskas JJ, Satanove A. Effect of topical agents on plantar sweating. Arch Dennato and Syphilology 1954; 69:713-6. 8. Salo K, Kang WH, Saga K, Sato KT. Biology of sweat glands and their disorders. II. Disorders of sweat Acta Dermatoven APA Vol 11, 2002, No 1 ----------------- --- - - 2.J Treatment