AAMJ Vol 8 N 2 April 2010 Suppl TREATMENT OF PRIMARY WITH BOTU - PDF document

AAMJ, Vol. 8, N. 2, April, 2010, Suppl. TREATMENT OF PRIMARY WITH BOTULINUM TYPE A TOXIN ABSTRACTPrimary palmar hyperhidrosis is an excessive sweating of the palms with an unknown etiology. Chemodnervation with botulinum toxin type A appears to offer a simple and safe treatment for palmar hyperhidrosis. 28 patients (19 female and 9 males) with primary palmar hyperhidrosis were treated in this study with botulinum toxin type A injections, under local anesthetic cream and as an out-patient clinic procedure. Follow-up of the patients continued up to 12 months post-injection. The antihydrotic response lasted from 5 to 9 months, with an average of 6 months. The study showed a maximum sweating reduction response of 87%, two weeks after treatment and the botulnium type A toxin has demonstrated to have an effective treatment alternative to the other conservative and surgical options for reducing sweating and treating the primary palmar hyperhidrosis, with transient Palmar hyperhidrosis is an excess

ive sweating of the palms beyond that required to cool the body. It is a common problem and frequently seen in adults. It can be emotionally challenging, socially embarrassing and printerfering with the patients social or work activity. It gives the impression of nervousness and in severe cases sweat drips from the hands. It is usually attributed to anxiety or emotional factors, but in most of the cases, it is not possible to determine a cause [1, 2]. Abdel-Sattar Al-Refae The pathophysiology of sweating is complex [3, 4, 5]. There are two types of sweat glands: 1.The apocrine sweat glands that are associated with hair follicles and play no part in thermoregulation. 2.The eccrine glands which play an important role in thermoregulation and are located throughout the body, but are concentrated in the palms, soles, and axillae. They are situated deep in the dermis and secret a dilute solution containing urea, lactic acid and sodium chloride [4]. The eccrine glands receive sympathetic innervati

on, and the neurotransmitter involved is acetyl choline. However, both eccrine and apocrine sweat glands have been shown to be stimulated by cholinergic as well as adrenergic agonists [3]. Primary palmar hyperhidrosis lacks a precise definition and is of unknown etiology. It usually involves the palms, soles, and axillae, where the glands are concentrated and show an exaggerated response to mental stimuli. Secondary hyperhidrosis is associated with obesity, menopause, drug use (antidepressants), endocrine disorders (hypoglycemia, hyperthyroidism, pheochromocytoma), and neurologic conditions involving autonomic dysregulation, such as syringomyleia, paraplegia, stroke, and other focal lesions in central nervous system [6, 7, 8, 9]. In our study, only the primary palmar hyperhidrosis cases were included and it was important to exclude thents before the treatment was initiated. Many treatments for primary palmar hyperhidrosis have been described, but few are effective and acceptable and

have been without potential complications [3, 10, 11]. Topical agents such as aluminum chloride may cause irritation, and tanning AAMJ, Vol. 8, N. 2, April, 2010, Suppl. agents are associated with staining. Iontophoresis may provide relief in palms hyperhidrosis but it is time consuming and requires numerous treatments and maintenance therapy [10].Systemic anti cholinergic agents frequently have unacceptable side effects. Upper thoracic sympathectomy often fails to cure palmar hyperhidrosis, and complications may include: pneumothorax, pneumonia, Horner's syndrome, and compensatory hyperhidrosis in non-innervated areas. Surgical excision and suction-assisted removal of sweat glands are not applicable in palmar hyperhidrosis, and associatar hyperhidrosis, and associat Botulinum toxin type A (a neurotoxin produced by the bacterium clostridium botulinum), is a safe alternative to surgical interventions, ongoing topical applications, or frequent treatment modalities for reducing palmar sweatin

g, with no significant complications or side effects [12]. It is a di-chain polypeptide that produces a dose-dependent blockage of presynaptic acetylcholine release, through binding of the heavy chain of the toxin to the presynaptic receptors [13, 14]. Its use has extended to include aesthetic and non-aesthetic applications, and is available commercially in two formulations: Botox Allergan Inc., Irvine, CA and Ispen Limited, Berkshire, England. Both are available in a lyophilized form and must be reconstituted with physiological sterile saline before use. Each vial of Botox contains 100 units of clostridium botulinum type A neurotoxin complex, 0.5 mg of human albumin, and 0.9 mg of sodium chloride, in a sterile vacuum dried form without a preservative [15]. Botulinum toxin type A (Botox, Allergan, Irvin, CA), was the type of choice, used in our study, for treating all the patients exndications to its Patients with peripheral motor neuropathic disease orb neuromuscular Hypersensitivity to h

uman albumin orbotulinum toxin. Abdel-Sattar Al-RefaePatients using extensive anti-inflammatory medicine (more bruising). Patients with inflammatory skin disorders at the injection site. Botox type A therapy is relatively contraindicated for co-administration with aminoglycoside antibiotics (may increase the effect of the botulinum toxin), pencillamine, quinine, chloroquine, and hydrochloroquine (may reduce the effect), calcium channel blockers, and blood thinning agents as warfarin or aspirin (may result in bruising), or any other agents that interfere with neuromuscucu PATIENTS AND METHODS Twenty-eight patients, with bilateral primary palmar hyperhidrosis were included in this study. 19 patients (68%) were females and 9 patients (32%) were males, ranging in age from 18 to 35 years with a mean age of 24 years. The study was conducted in the period from 2006 to 2008, in Saudi Arabia. All patients were evaluated medically with particular attention given to possible neurological or endocrine

diseases and any suspected case of secondary palmar hyperhidrosis or any contraindication to the use of botulinumtoxin type A, was excluded from the Detailed counseling was discusse1.The treatment plan and the overall aesthetic goals, with realistic expectations for the treatment outcome. 2.The desired and potential adverse effects of the botulinumtoxin injection procedure and the longevity of the results, paying the attention of the patient to the long history of the safe use, the low probability of any of these effects occurring, and the fact that most of adverse effects are mild and transient. AAMJ, Vol. 8, N. 2, April, 2010, Suppl. 3. Avoiding the medications that inhibit clotting such as vitamin E, aspirin, and non-steroidal anti-inflammatory drugs (NSAIDs), for a period of 10-14 days prior to treatment, to reduce ed not to message the treatment area after injection. On the day of the procedure, a detailed consent form was completed and signed. The consent included the approval t

o take photographs, the type of botulinum toxin, longevity expected, the need for repeated treatments and the possible post-s, and complications. Pre-injection *Reconstitution of the botu Botox; Allergan was provided for the study in vials 100 units of vacuum-dried neurotoxin complex. The toxin was reconstituted with normal saline, directly before the procedure, to a concentration of 40 units per 1 ml (dilution of 2.5 ml normal saline:100 units vil saline:100 units vill prescribing information states that botulinum toxin type A should be used within 4 hours of reconstitution, the clinical experience and published data suggest that potency can be maintained for up to six weeks with proper storage [18]. Agitating, shaking or foaming the vial during reconstitution was avoided although some studies suggest they do not impact the potency [19]. One of the main disadvantages with treatment of palmar hyperhidrosis is pain with injection. The free nerve endings responsible for the pain sensation

occur in the papillary dermis and epidermis, whereas the sweat glands are imbedded deep in the dermis and in the upper layer of the subcutaneous tissue[20]. The cutaneous areas of the palms were treated with a mixture of local anesthetic (EMLA cream) prior to injection, or chilled with ice packs to minimize pain and stinging. All the usual precautions of sterility and skin preparation before injection were followed. Marking of the injection sites of both palms was done, with an average of 35-50 Abdel-Sattar Al-Refaesites per palm, and 1.5-2 cm apart. The total amount of botulinum toxin, to be injected for each palm, was calculated and ranged from 80-120 units, with an average of 100 units per palm, depending on the surface area. The toxin was freshly reconstituted and a 30-gauge needle on 1 ml insulin syringe was used for the injection procedure. With the bevel facing up-wards, the needle penetrates the skin tangentially, and is then advanced for about 2 mm before injection. The thumb is

taken off the syringe plunger for a second or two before withdrawal, to prevent the back flow of the botulinum t t Intradermal/subdermal injections were done with an optimal effort to deliver the toxin as close as to the sweat glands and presumably less painful than more superficial injections. A small zone of visible blanching attests to the deep dermal injection. However, the deeper the injection the greater the risk of causing weakness of the small muscles of the hand and weakening of the grip [21, 22, 23, 24]. Injections of the tips of the fingers were performed superficially due to the *Post-injection instructions: Post-injection ice compresses were applied on the palms to and minimize the injection pain and the patients were advised not to message the treatment area. An immediate post-injection information chart was added to the file The exact anatomical location for each injection. Dosage in units that was delivered in each palm. The total dose administered. AAMJ, Vol. 8, N. 2,

April, 2010, Suppl. Post-injection follow-up visits were scheduled for all patients at 2 weeks, 4 weeks, and then monthly up to12 months post-injection, for detailed observation of the anhydrotic response as well as any adverse effects or complications, and post-RESULTS A total of 28 patients, with moderate to severe primary palmar hyperhidrosis, were treated in the study. 19 patients were females and the other 9 patients were males, with an age ranging from 18 to 35 years with a mean age of 24 years. The total amount of botulinum toxin type A injected ranged from 80 to 120 units per palm with an average of 100 units per palm. The anhydrotic response was evaluated for all patients at 2 weeks, 4 weeks, and then monthly up to 12 months nhydrotic effect duration ranged from 5 to 9 months. 23 patients (82%) showed a maximum palmar sweating reduction (a mean of 87%), 2 weeks after treatment and the other 5 patients (18%) have shown a maximum response after 5 weeks. The average long-lasting a

nhydrotic effect duration was 6 months, in 22 patients (78.6%), 8 months in 3 patients (10.7%), 9 months in 2 Transient weakness of the small muscles of the hand with quicker fatigue and weakening of the grip, when using the hands, was reported in 4 cases (14.3%), and lasted up to 8 weeks post-injection, but this was reduced by avoiding the deeper injections with injection of smaller quantitieantitie Minimal bruising and swelling around the injection site was reported in 3 cases (10.7%) and this was minimized by instructing the patients to avoid aspirin and other anti-inflammatory antiplatelet medications 2 weeks before treatment. Abdel-Sattar Al-Refae The injection was uncomfortable and painful to 6 patients (21.4%) in the study, and this was reduced by using the local anesthetic EMLA cream and or chilling the In our study, we have not seen any patient who have developed allergic or stance to the botulinum A of antibody formation has been reported to be between 3 – 5 %, and thi

s seems to occur with extrem�ely large doses 300 units within a 30 days period [26]. Unlike sympathectomy, which renders more than 20% of the body surface anhydrotic, the selective local chemodenervation achieved by injecting the botulinum type A toxin to combat the localized sever sweating of the palms, does not precipitate a compensatory hyperhidrosis in any case of the study, as the total surface area treated was less than 3%. There have been no local infection, systemic effects, or any case failure, and the adverse effects of the toxin injections resolved within 2 months, and have been minimal compared to the efficacy and high patient satisfaction. Overall, the 28 patients treated in this study, achieved a high long-lasting anhydrotic effect and the botulinum toxin type A injections appears to be an effective, safe, simple, and minimally invasive procedure, performed in the clinic for treating the primary palmar hyperhidrosis as well as an ideal alternative to other treatment

modalities (table-1). AAMJ, Vol. 8, N. 2, April, 2010, Suppl. Table-1: Primary palmar hyperhidrosis study: Patients and Results. Patients: * Females: 19 patients (68%). *Age: 18-35 years (a mean Toxin used: Botulinum toxin Allergan, Irvin, CA) * Dosage per palm: 80-120 units (average of 100 units per palm. (EMLA cream). * Maximum anhydrotic (87%). - For 5 months: 1 patient (3.55%). - For 6 months: 22 patients (78.6%). - For 8 months: 3 patients (10.7%). - For 9 months 2 patients (7.15%). * Weakness of palmar

4 patients (14.3%). small muscles: * Bruising: 3 patients (10.7%). * No local infection, systemic effects, compensatory Abdel-Sattar Al-Refae (A) Fig.(1-Aand B).(A): Pre-injection of primary palmar hyperhidrosis of right hand of a female patient 24 years old.(B):4weeks post-injection using botulinum type (A) toxin (Botox), with complete dry hand. AAMJ, Vol. 8, N. 2, April, 2010, Suppl. Fig.(1-C): Botulinum type (A) toxin(Botox) vial (100 units), diluted with saline and ready for injection. Abdel-Sattar Al-Refae (D) Fig.(1-D and E). (D): Marking of right hand. (E):Injection of right hand using botulinum type (A) toxin (Botox). AAMJ, Vol. 8, N. 2, April, 2010, Suppl. (F) Fig.(1-F and G). (F): Pre-injection of primary palmar hyperhidrosis of left hand of a female patient 24 years old.(G):4 we

eks post-injection using botulinum type (A) toxin (Botox), with complete dry hand. Abdel-Sattar Al-Refae (H) Fig.(1-H and I). (H): Pre-injection of primary palmar hyperhidrosis of both hands of a female patient 24 years old. (I): 4 weeks post-injection using botulinum type (A) toxin (Botox), with complete dry hands. AAMJ, Vol. 8, N. 2, April, 2010, Suppl. (A) primary palmar hyperhidrosis of right hand of a male patient 32 years old.(B):4 weeks post-injection using botulinum type (A) toxin (Botox), with complete dry hand. Abdel-Sattar Al-Refae (C) primary palmar hyperhidrosis of left hand of a male patient 32 years old.(D):4 weeks post-injection using botulinum type (A) toxin (Botox), with complete dry hand. AAMJ, Vol. 8, N. 2, April, 2010, Suppl. (E) primary palmar hyperhidrosis of both h

ands of a male patient 32 years old.(F):4 weeks post-injection using botulinum type (A) toxin (Botox), with complete dry hands. Abdel-Sattar Al-RefaeDISCUSSION Primary palmar hyperhidrosis is an excessive sweating of the palms and can give impression of nervousness and a wet grip can be hazardous at work. It is of unknown etiology and usually involves the palms, where the eccrine glands are concentrated and show an exaggerated response to mental stimuli. The condition is an emotionally disruptive and there have been few effective treatments. Botulinum toxin type A injection has been demonstrated to be an effective treatment for primary hyperhidrosis of the palms. It offers minimal side effects compared to the other coared to the other co The procedure was adopted in our study, where 28 patients, with moderate to severe primary palmar hyperhidrosis were treated, using botulinum toxin type A injections. Any suspected case of secondary hyperhidrosis was excluded from the study before treat

ment was initiated. An advantage of botulinum toxin injection (focal chemical denervation of the sweat glands), It eliminates the other ongoing treatment modalities and medications as well as it can be performed during a routine office visit, with local anesthetic cream and minimal discomfort [27]. The total amount of botulinum toxin A units injected, in our study, ranged from 80-120 units with an average of 100 units per palm, and a maximum anhydrotic response reduction of 87% in 23 patients (82%), 2 weeks after treatment and lasted for an average of 6 months in 22 patients (78.6%), 8 months in 3 patients (10.7%), 9 months in 2 patients (7.15%), and 5 months AAMJ, Vol. 8, N. 2, April, 2010, Suppl. in 1 patients (3.55%). Nauman et al. [20, 21, 23], used a total amount of botulinum toxin injection ranged from 36-120 units per palm, injected in 16-50 sites, with the distance between sites ranging from 1 to 2 cm. The anhydrotic response has only been quantitated in a few studies and in only o

ne double-blinded study [23]. Gravimetrically assessed sweating declined 85%, 2 weeks after treatment [21, 23]. In a different study, subjective ratings by the patients have shown improvements, from a mean of (79.3% to 67%), 6 weeks after treatment [23, 24]. The duration of anhydrotic effect has, in some studies, lasted from 13 weeks to9 months [20, 24, 25], and in certain patients, persisted for up to 12 months [20, 21, 23, 24]. One of the main disadvantages with treatment of palmar hyperhidrosis was the pain during injection. The injection was untolerable and painful to 6 udy, this was reduced by using EMLA cream and or chilling the palms with ice packs before injection combined with an optimal delivery of the botulinum toxin in subdermal injections as close to the sweat glands as possible, which would be less painful than more superficial injections. Shelly et al. 1998,used nerve blocks of the median and ulnar nerves at the wrist, with 1% lidocaine 30 minutes before the subepidermal inje

ction [20]. In contrast, intradermal/subcutaneous injections have been given without anesthetics [22, 24], or cold packs were placed on the palms to minimize pain [23]. Other studies [25] have used regional anesthesia of the median and ulnar nerves before Another disadvantage in treating the palmar hyperhidrosis with botulinum toxin injections was the transient muscle weakness and quicker fatigue of the hands, that was reported in the study in 4 cases (14.3%), and lasted for 8 weeks, and it was attributable to the dose and deeper injection. Numerous studies [20, 22, 23, 24], have reported the weakness of the small muscles of the hand and suggested that it can be potentially reduced by injecting smaller Abdel-Sattar Al-Refaequantities per site at more frequent intervals [23]. However, the botulinum toxin type A manufacturer's recommended frequency of injections is every 2 months, due to the potential for antibody development. Odderson1998 suggested that: quantitating the sweat rate per area

may be useful to determine the optimal dose for different severities of palmar hyperhidrosis ar hyperhidrosis We have experienced a high satisfaction rate in treating the primary palmar hyperhidrosis, using the botulinum toxin type A, and the adverse effects of the procedure were transient and minimal. CONCLUSION Treatment of primary palmar hyperhidrosis with botulinum toxin type A injections, is a safe, easily performed procedure in the clinic, minimally invasive, and effective alternative to other treatment modalities, with a minimal and transient adverse effectEFERENCES Lin CC. A new method of thor n AAMJ, Vol. 8, N. 2, April, 2010, Suppl. hyperhidrosis palmaris. Surg Doolabh N, Horswell S, Williams M, Huber L, Prince S, Meye r et al. Thoracoscopic sympathectomy for hyperhidrosis: 3. Mausov KG, Nadeau MT. Hyperhidrosis: a management dilemma. J Fam 4. Greenhalgh RM, Rosengarten DS, Martin P. Role of sympathectomy for 5. Sato K, Kang WH, Saga K, Sato KT. Biology of sweat glan

ds and their disorders. I. Normal sweat gland function. J Am Acad Dermatol., 20:537-6. Hurley HJ. Diseases of the eccrine sweat glands. In: Moschella SL, Hurley HJ, eds. Dermatology, 3 ed. Philadelphia: WB Saunders, 1514-7. Korpelainen JT, Sotaniemi KA, Myllyla VV. Asymmetric sweating in stroke: a prospective quantitative study of patients with hemispheral brain 9. Sato K, Kang WH, Saga K, Sato KT. Biology of sweat glands and their disorders. II. Disorders of sweat glands and their function. J Am Acad Dermatol., 20:713-2, 1989. 10. Holzle E, Ruzicka T. Treatment of hyperhidrosis with battery-operated iontophoretic device. Dermatologica., 172:41-7, 1989. 11. Moran KT, Brady MP. Surgical management of primary hyperhidrosis. Abdel-Sattar Al-Refae12. Nauman M, Zellner M, Toyka KV, Reiners K. Treatment of gustatory sweating with botulinum toxin. Ann Neurol., 42:973-, 1997. 13. Dolly JO. Theraputic and research exploitation of botulium neurotoxins. Eur J Neurol., 4(suppl):S5-1, 1997. 14. Odderson

IR. Hyperhidrosis treated by botulinum A exotoxin. Dermatol Shetty MK. Guidelines on the use of botulinum toxin Type A. Indian J DermatolVenereolLeprol.,74:13-22, 2008.16. James E. Fulton. Utilizing botulinum toxin in our cosmetic surgery practice. Cosmetic Dermatol.,10, No.4:44-46, 1997. 17. Klein AW. Dilution and storage of botulinum toxin. Dermatol 18. Hexsel DM, de Almeida AT, Rutowitsch M, De Castro IA, Silveira VL, Gobatto DO, et al . Multicenter, double-blind study of the efficacy of injections with botulinum toxin type A reconstituted up to six ion. Dermatol Surg., 29:523-9, 2003. 19.Trindade de Almeida AR, Kadunc BV, Di Chiacchio N, Neto DR. Foam during reconstitution does not affect the potency of botulinum toxin type A. Dermatol Surg., 29:530-1, 2003. 20. Shelley WB, Talanin NY, Shelley ED. Botulinum toxin therapy for palmar hyperhidrosis. J Am Acad Dermtol., 38:227-, 1998. 21. Nauman M, Hofmann U, Bergman I, Hamm H, Toyka KV, Reiners K. Focal hyperhidrosis. Effective treat

ment with intracutaneous botulinum AAMJ, Vol. 8, N. 2, April, 2010, Suppl. toxin. Arch Dermatol., 134:301-4, 1998. 22. Nauman M, Flachenecker P, Brocher EB, Toyka KV, Reiners K. Botulinum toxin for palmar hyperhidrosis. Lancet, 349:252, 1997. 23. Schneider P, Binder M, Auff A, Kittler H, Berger T, Wolf K. Double-blind trial of botulinum A toxin for the treatment of focal hyperhidrosis 24. Schneider P, Binder M, Kittler H, Steinoff N, Auff E. Use of botulinum 25. Naver H, Aquilonius SM. The treatment of focal hyperhidrosis with botulinum toxin. Eur J Ne26. Bilitzer A, Brin MF, Keen MS, Aviv JE. Botulinum toxin for the treatment of hyperfunctional lines of the face. Arch Otolaryngol Head 27. Bilitzer A, Binder WJ, Brin MF, Aviv JE, Keen MS, Brin M. The management of hyperfunctional facial lines with botulinum toxin. Arch يلوϷايعافرلاراتسلادبع Abdel-Sattar Al-RefaeقورحلاقرعتشلاديدمييقتسكتوبلاجϼعقرعتلايضرمسكتوبلاةيجϼعلاØ