Botulinum Toxin for Hyperhidrosis

Primary focal hyperhidrosis is a disorder of idiopathic excessive sweating that typically affects the axillae, palms, soles, and face. The disorder, which affects up to 2.8% of the US population, is associated with considerable physical, psychosocial, and occupational impairments. Current therapeutic strategies include topical aluminum salts, tap-water iontophoresis, oral anticholinergic agents, local surgical approaches, and sympathectomies. These treatments, however, have been limited by a relatively high incidence of adverse effects and complications. Non-surgical treatment complications are typically transient, whereas those of surgical therapies may be permanent and significant. Recently, considerable evidence suggests that botulinum toxin type A (BTX-A) injections into hyperhidrotic areas can considerably reduce focal sweating in multiple areas without major adverse effects. BTX-A has therefore shown promise as a potential replacement for more invasive treatments after topical aluminum salts have failed. This article reviews the epidemiology, diagnosis, and management of primary focal hyperhidrosis, with an emphasis on recent research evidence supporting the use of BTX-A injections for this indication.     

A型肉毒毒素皮内注射治疗多汗症

目的　介绍A型肉毒毒素皮内注射治疗多汗症。方法　重点介绍A型肉毒毒素注射治疗手掌多汗症和腋部多汗症。结果　A型肉毒毒素皮内注射治疗多汗症 ,注射后 2～ 3天即止汗 ,5～ 7天止汗明显 ,平均可维持 9～ 12个月。大剂量注射可维持更长时间。结论　A型肉毒毒素皮内注射是治疗手掌多汗症和腋部多汗症安全、有效的治疗方法。     

肉毒毒素在美容皮肤科除皱上的应用

肉毒毒素(BT)用在美容除皱上已有20年历史,它于1997年引进到美容皮肤科,肉毒毒素所以能除皱是BT阻断突触释放乙酰胆碱而使肌肉麻痹,肉毒毒素有4种产品,BTA:关国Botox,中国衡力,英国Dysport,BTB:美国Myobloc。最早用于面上1/3皱纹,从眉间纹开始,以后用于面中部、面下部、颈部和胸部皱纹。经过培训,严格操作,肉毒毒素除皱安全而有效。     

Botulinum Toxin

Patient satisfaction with botulinum toxin treatment is a key success factor in aesthetic procedures and is governed by the interaction of numerous variables. Duration of effect is important because it influences retreatment intervals as well as affecting cost and convenience to the patient. In order to review the evidence on the duration of benefit associated with various commercial formulations of botulinum toxin, MEDLINE was searched using the following terms: ‘botulinum’ and ‘duration’/‘retreatment’ (limits: ‘clinical trials,’ ‘meta-analyses,’ ‘English’). I also searched my existing reference files, reference lists of identified articles, and meeting/conference abstracts to ensure completeness. The focus was on clinical medicine and aesthetic trials. To be eligible for the analysis, studies had to include efficacy assessments at multiple timepoints. To estimate duration of benefit, the following outcomes were examined and summarized: responder rates, mean wrinkle severity scores at various timepoints (with or without changes from baseline), and relapse rates. Duration at both repose and maximum attempted muscle contraction was considered when provided. Where possible, duration was assessed by formulation and dose. The initial search yielded 164 articles. Of these, 35 included an adequate measure of duration in aesthetic indications. The majority of these (22) were on the glabellar area. Study designs and endpoints were highly heterogeneous, and duration of effect varied between studies. Several studies with the BOTOX® Cosmetic (onabotulinumtoxinA; Allergan, Inc., Irvine, CA, USA) formulation of botulinum toxin type A (BoNTA) included relapse rates, defined conservatively as return to baseline levels of line severity for two consecutive visits approximately 30 days apart (at repose and maximum contraction). In these studies, duration of effect ranged from 3 to 5 months in female patients and from 4 to 6 months in male patients. Individual patients had longer durations of response. Across all studies providing relapse rates, most patients relapsed by 6 months. In studies assessing patient satisfaction, satisfaction remained high throughout the duration of the studies (～4 months). With the Dysport® formulation (abobotulinumtoxinA, clostridium botulinum type A toxin-hemagglutinin complex; Ipsen Biopharm Ltd, Wrexham, England), retreatment intervals were estimated at a mean of 3.9 months (median = 3.3 months). These results were consistent with responder rates from another Dysport® study in which the active treatment differed from placebo at 3 but not 4 months. A single comparative study demonstrated that the proportion of patients relapsing at week 16 was 23% (95% CI 11.5, 41.6) in the BOTOX® Cosmetic group as compared with 40% (95% CI 25.2, 60.1) in the Dysport® group. Myobloc® (rimabotulinumtoxinB, botulinum toxin type B; Solstice Neurosciences, Inc., South San Francisco, CA, USA) was associated with shorter durations of action (2–3 months). Data from facial areas other than the glabella, although more limited, supported a duration of at least 3–4 months. The addition of BoNTA to dermal fillers or light/laser therapy appeared to increase the degree of effect. Repeated BoNTA treatments may prolong duration of effect or potentiate the effect. In conclusion, patients can expect treatments to last ≥3 months but often as many as 4–5 months depending on the facial area, dose, and formulation. Additional research should help clarify the impact of age, baseline rhytid severity, patient sex, repeated treatments, and combination treatment on longevity of effect.     

Palmar Hyperhidrosis: Long-term Follow-up of Nine Children and Adolescents Treated with Botulinum Toxin Type A

Abstract:   Primary palmar hyperhidrosis in children and adolescents may be severe enough to affect school and physical activities, causing emotional problems, stress in the patient's life, and a compromised quality of life. Nine patients with palmar hyperhidrosis underwent treatment with botulinum A. Before the session, and in the 1-, 3-, 6-, 9-, and 12-month post-session follow-ups, the patients were administered the Minor test, gravimetry, the Scales of Frequency and Severity, and the Questionnaire of Quality of Life. The mean age was 11 years, with seven girls and two boys. Each patient was administered at least one treatment of botulinum toxin in the palm of the hands (75–150 U for palm), with the mean number of sessions 2.2 (range: 1–4). All sessions in the patients resulted in drying of the hands, with a mean duration of effect of 7 months. Botulinum toxin A controls excessive sweat in the palms of children and adolescents who have primary palmar hyperhidrosis, with an improvement in the quality of life. The therapy is safe and effective in this pediatric group and can be considered before surgical interventions.     

Update on Botulinum Toxin

Botulinum toxin type-A (BTX-A) is a neurotoxin which blocks presynaptic release of acetylcholine. It interferes with neuromuscular transmission, temporarily paralyzing the affected muscle. Of special interest for dermatologists is the unlabelled cosmetic applications, for conditions such as wrinkles and hyperhidrosis. Labelled indications in Europe are for cervical dystonia and cerebral palsy. In the US, it is approved for treatment of strabismus, blepharospasm and hemifacial spasm in adults. After repeated use of high doses, antibodies can develop in some individuals, making further treatment ineffective indefinitely. Even when used in high does for neurological conditions, the development of antibodies occurs in < 5&percnt of patients. In 1997, the US FDA approved a new bulk toxin source for use in the manufacture of BTX-A. It has a higher specific potency than original BTX-A formulations, reducing the amount of utilized neurotoxin protein, and thereby reducing antibody production. Another form of this neurotoxin (type B) also appears to be effective in patients who have developed antibodies to BTX-A. It is awaiting US FDA approval for treatment of cervical dystonia.     

Botulinum Toxin for Glabellar Lines

Facial rhytides represent a widespread aesthetic concern. In particular, glabellar lines are perceived as a sign of aging and may give an erroneous impression of negative emotions. The onset of glabellar lines is closely related to the movements of the underlying muscles. Botulinum toxins inhibit the release of acetylcholine into the synaptic cleft and therefore result in temporary muscle paralysis. The observation that botulinum toxin (BTX) smoothed facial lines when used therapeutically led researchers to study the toxin effect on glabellar lines. Nowadays, the use of BTX to smooth glabellar frown lines represents the leading procedure in aesthetic facial treatments and an increasing number of BTX formulations are becoming available. This article provides a comparative evaluation of currently available BTX options for the treatment of glabellar lines. Toxins have been divided into three groups, based on whether they have obtained approval for cosmetic use (approved treatments) or not (off-label treatments), or whether they are still under investigation (experimental treatments). We examine the basic similarities and differences between available botulinum toxins, and summarize the pharmacokinetics and dosing. All approved treatments consist of BTX type A (BTX-A) and differ in their molecular weight, as some formulations are made of a BTX-A complex of 900 kDa while the latest option on the market is a 150 kDa BTX-A that is free from complexing proteins. As for the dosage, the important aspect that emerges from this comparison is that even within a given serotype, such as BTX-A, formulations are not interchangeable as each possesses distinctive characteristics that are attributed to the unique toxin purification and manufacturing processes. There is a substantial body of published evidence on the use of these approved treatments for facial enhancement, proving efficacy and safety. We investigate the methods of evaluation used for each toxin and review the safety and efficacy data reported in the literature. Minor adverse effects, such as headache, blepharoptosis, and injection-site reactions, are relatively frequent but transient, whilst major adverse effects are rare. Some botulinum toxins, i.e. BTX type B, that are approved for therapeutic applications are used off-label for cosmetic indications, thus without the approval of the health regulatory committees and without sufficient published evidence on safety and efficacy. As for experimental treatments, a number of BTX products are currently in development or have been recently launched for aesthetic applications. These products have been specifically designed to overcome some of the limitations present in the older generation of products. However, some of these toxins may be easily purchased via the Internet, without having any license or approval for cosmetic or therapeutic indications; these products must be considered unsafe and are potentially a severe health risk for patients.     

Quality of Life and Social Isolation in Greek Adolescents with Primary Focal Hyperhidrosis Treated with Botulinum Toxin Type A: A Case Series

Primary hyperhidrosis, although extensively documented in adults, typically has onset that dates back to early childhood. It is an unpleasant and socially disabling problem for the affected child, but little attention has been paid to the disease in adolescents. The objective of the current study was to evaluate the effectiveness of botulinum toxin type A (BTXA) in adolescents with primary palmar and axillary hyperhidrosis and to determine its effect on quality of life and social isolation. Thirty‐five individuals (17 girls, 18 boys) with moderate to severe palmar and axillary hyperhidrosis were treated with BTXA (onabotulinum). Patients were examined at baseline and 6 months after treatment. The Hyperhidrosis Disease Severity Scale (HDSS) was used to evaluate disease severity and the Children's Dermatology Life Quality Index (CDLQI) was used to assess quality of life. The University of California at Los Angeles loneliness scale (UCLA version 3) was used to assess personal perception of loneliness and social isolation. The median age of the participants was 14 years, and 48.6% were female. Twenty‐one had palmar hyperhidrosis, and 14 had axillary hyperhidrosis. Total CDLQI and social isolation scores decreased significantly after treatment with BTXA (both p < 0.001). There was a significant difference between pre‐ and post‐treatment levels of severity of hyperhidrosis. No statistically significant difference was documented for CDLQI and UCLA scores between boys and girls. Treatment of hyperhidrosis with BTXA resulted in improvement in quality of life, social skills, and activities.     

A型肉毒毒素治疗Meige综合征及面部皮肤除皱临床研究

目的观察A型肉毒毒素(BTXA)治疗Meige综合征及面部皮肤除皱的疗效,探讨降低药物副作用的发生及BTXA皮肤除皱的作用。方法对99例患者应用BTXA局部多点注射。结果治疗眼睑痉挛型、口下颌肌张力障碍型及眼睑痉挛并口下颌肌张力障碍型的显效率分别为98.4%、90.9%和95.8%。疗效持续时间分别为(16.9±8.4)周、(12.6±5.4)周和(13.5±5.7)周。面部皮肤除皱有效率100%,皮纹变浅、变平且光滑。局部副作用轻微、短暂且可自行消失。结论BTXA治疗Meige综合征及面部皮肤除皱疗效显著且安全性好。严格操作规程及掌握适当剂量能降低药物副作用的发生。     

Managing Adverse Events Associated with Botulinum Toxin Type A

Botulinum toxin A (BTXA) has become a widely used drug in cosmetic dermatology, not only to treat focal hyperhidrosis but also hyperkinetic facial lines, platysma bands, décolleté bands, and other skin features. The spectrum of possible adverse effects of BTXA is broad but fortunately those that have been observed with cosmetic use of this product are generally mild and transient. The major tools for preventing adverse effects from BTXA are knowledge and skill. Use of correct injection techniques is mandatory since most unwanted effects are caused by incorrect technique. Knowledge of the target structures, e.g. the facial and extrafacial muscles, allows physicians to select the optimal dose, time and technique. The most common adverse effects are pain and hematoma. In the periocular region, lid and brow ptosis are important adverse effects. Adverse effects such as pain, hematoma, ecchymosis, and bruising may also occur in the upper and lower face and at extrafacial sites. Other possible adverse effects seen in other indications that the user of BTXA in cosmetic dermatology should be wary of include induction headaches and possible interaction with concomitant medications. Induction of neutralizing antibodies due to cosmetic BTXA treatment has not been observed. This article also outlines recommendations regarding use of BTXA. Of these, the most important for avoiding most unwanted adverse effects are the proper techniques of dilution, storage, and injection, as well as the careful exclusion of patients with any contraindications. Pain, hematoma, ecchymosis, and bruising can be prevented by cooling the skin before and after BTXA injection. Upper lid ptosis may be partly corrected using apraclonidine or phenylephrine eyedrops. If simple rules relating to the indications for and application of BTXA are followed, this is a safe and effective drug in cosmetic dermatology.     

A型肉毒素治疗瘢痕增生的疗效和安全性分析

目的武汉市第九医院探讨A型肉毒素治疗机体瘢痕增生的临床疗效和安全性。方法 2014年6月—2015年6月,我科共收治80例增生性瘢痕患者,随机分为观察组和对照组,每组40例,对照组采用曲安奈德局部注射治疗,观察组采用A型肉毒素局部注射治疗,比较2组临床疗效,病理表现,并观察复发情况和不良反应发生情况。结果观察组总有效率高于对照组,组间差异有统计学意义(P0.05);与治疗前相比,2组治疗1~5次后,瘢痕长轴逐渐缩短,组内差异均有统计学意义(P0.05);治疗前两组瘢痕长轴长度差异无统计学意义(P0.05);每个时间点观察组瘢痕长轴长度短于对照组,组间差异均有统计学意义(P0.05);2组不良反应发生率无统计学意义(P0.05);6个月内,观察组复发率低于对照组,差异有统计学意义(P0.05)。结论 A型肉毒素治疗机体瘢痕增生临床疗效佳,不良反应少,具有广阔的临床应用前景。     

Exaggeration of Wrinkles after Botulinum Toxin Injection for Forehead Horizontal Lines

There have been no long-term complications or life-threatening adverse effects related to botulinum toxin treatment for any cosmetic indications. Nevertheless, there are well-known, mild side effects of botulinum toxin treatment on the upper face, though most of them are self limited with time. However, excluding brow ptosis, reports about site specific side effects are few and anecdotal. We experienced cases of exaggeration of wrinkles after botulinum toxin injection for forehead horizontal lines, and report them here. In our cases, new appearance of a noticeable glabellar protrusion following botulinum toxin injection on the forehead was observed in 2 patients. Also, a new deep wrinkle on one side of the forehead just above the eyebrow appeared in another 2 patients. The exaggerated wrinkles nearly disappeared without treatment by week 4 in all subjects. These exaggerations of wrinkles may be caused by hyperactivity and overcompensation of untreated muscles. With the increasing availability of diverse botulinum toxin for cosmetic purposes, physicians and patients should be aware of this temporary change after therapeutic injections. We recommend explaining this possible effect prior to injection, for better understanding of treatment for cosmetic indications.