Dilution Volume of Botulinum Toxin Type A for the Treatment of Glabellar Rhytides: Does It Matter?

BACKGROUND Because well-controlled studies examining the efficacy and safety of various dilutions of botulinum toxin type A (BTX-A) have not been performed, dilutions used in clinical practice are chosen at the discretion of the clinician.
OBJECTIVES The objectives were to determine the most effective BTX-A dilution for the glabellar region, the relationship between dilution and duration of effect, and the side effect profile of each dilution in women with glabellar rhytides.
METHODS Eighty women with moderate-to-severe wrinkles at maximum frown were randomized to one of four dilution groups in a 48-week, single-center, double-blind, parallel-group study. Subjects received 30 U BTX-A (BOTOX, Allergan, Inc.) injected into the glabellar region at dilutions of 100, 33.3, 20, or 10 U/mL. Outcome measures included trained-observer and subject assessment of wrinkle severity at repose and at maximum muscle contraction using the Facial Wrinkle Scale (FWS) and adverse events.
RESULTS All dilutions of BTX-A effectively improved glabellar rhytides as assessed by both trained observers and subjects using the FWS. No significant differences on FWS scores were seen among the dilution groups by trained observers at any time point. Although a difference among groups was seen in subject-assessed responder rates, there was no obvious relationship between dilution and response. BTX-A treatment was well tolerated, and there were no significant differences between the four dilution groups in the number of subjects reporting adverse effects.
CONCLUSION In this study, the dilution of BTX-A was not critical to the success of treatment.     

Clinical Efficacy of Botulinum Toxin Type A Reconstituted and Refrigerated 1 Week before Its Application in External Canthus Dynamic Lines

BACKGROUND Allergan Inc. recommends that its botulinum toxin type A (BTX-A; BOTOX) must be refrigerated and applied within 4 hours after its reconstitution to avoid losing its biologic effectiveness.
OBJECTIVE The objective was to compare clinical efficacy in treating external canthus dynamic lines with reconstituted and refrigerated toxin (BTX-A) 1 week before its application versus fresh toxin (BTX-A).
METHODS This study was a double-blind, randomized, clinical trial. A total of 30 patients aged 30 to 60 years having a minimum of one and maximum of six external canthus dynamic lines were treated in one canthus with 15 U of BTX-A reconstituted and refrigerated at 4°C 1 week before being applied and in the other with 15 U of fresh BTX-A. Patients were followed-up on Day 10 and Weeks 6, 12, and 18; assessment included a neuroconduction study of the facial nerve and the investigators' photographic evaluation of the number of external canthus dynamic lines at maximum smile.
RESULTS Outcome measurement did not show statistically significant differences between both groups.
CONCLUSION BTX-A, reconstituted and refrigerated 1 week before its application, has similar clinical efficacy in treating external canthus dynamic lines as does fresh BTX-A.     

Antibody-Induced Failure of Botulinum Toxin Type A Therapy in a Patient with Masseteric Hypertrophy

BACKGROUND With the expanding use of botulinum toxin, much concern about the antibody against botulinum toxin is arising. Unlike neurologic indications such as cervical dystonia, antibody-induced failure of botulinum toxin therapy has never been reported in the cosmetic field.
OBJECTIVE The objective was to describe a case of an antibody-induced failure of botulinum toxin type A (BTX-A) therapy (BOTOX, Allergan, Inc.) that occurred in a patient with masseteric hypertrophy.
METHODS AND MATERIALS We present a 20-year-old girl who developed antibody-induced therapy failure after the fourth injection series. Sixty units of toxin was injected at each series and the intertreatment interval was four to five months.
RESULTS Frontalis test revealed no paresis of muscle after a unilateral injection of BTX-A. Circulating antibodies against BTX-A were detected by indirect enzyme-linked immunosorbent assay and mouse protection assay.
CONCLUSION This case is unique in that, first, immunoresistance developed in a patient of cosmetic indication where only a small dose of BTX-A was administered and, second, antibodies developed on the so-called new formulation of BOTOX. Our case alerts cosmetic surgeons to the importance of antibody against the botulinum toxin.     

Eyebrow Height after Botulinum Toxin Type A to the Glabella

INTRODUCTION Botulinum toxin type A (BTX-A) has demonstrated impressive safety and efficacy for the treatment of dynamic facial rhytides, particularly in the upper face. Numerous reports have cited an associated brow lift with BTX-A injections in the glabellar complex, presumably caused by deactivation of the brow depressor muscles. Few analyses examining this phenomenon more closely exist, however.
OBJECTIVE The objective was to examine objective changes in eyebrow and eyelid height following BTX-A treatment for glabellar rhytides.
METHODS A retrospective analysis of subjects' photographs taken during a single-center, dose-ranging, parallel-group, double-blind, randomized trial with 1-year follow-up in which women with moderate-to-severe wrinkles at maximum frown received a total of 10, 20, 30, or 40 U BTX-A in seven sites in the glabella alone. Photographs of the eyes and forehead region were taken in repose at baseline and every 2 weeks after treatment for up to 20 weeks. Eyebrow height was measured at midpupillary line ("a"), outer edge ("b"), and medial canthus ("c"). Changes in eyebrow height between baseline and after treatment were recorded for each subject. Brow lift was considered successful if measurements "a" and "b" increased after treatment.
RESULTS A total of 79 women were assessed. Central injections of 20 to 40 U BTX-A into the glabella alone (with the most lateral injection at the midpupillary line) led to an immediate lateral eyebrow elevation, followed by a central and medial eyebrow elevation that peaked at 12 weeks after treatment. The lowest dose of BTX-A (10 U) produced an initial mild brow ptosis and the weakest response.
CONCLUSION Doses of 20 to 40 U BTX-A produced dramatic changes in eyebrow position that may be due to diffusion of BTX-A into and partial inactivation of the medial fibers of the frontalis, with resulting increased muscle tone in the lateral and superior muscle fibers of the frontalis.     

Apocrine Carcinoma, Adenopathies, and Raised TAG-72 Serum Tumor Marker

Background. The detection of tumor-associated glycoprotein-72 in the serum of patients with carcinomas, basically of the colon, has proved to be of great use in the follow-up of these gastrointestinal adenocarcinomas.
Results. We report the case of a male patient presenting adenopathies in the right axilla. The histologic study of an adjacent skin tumor enabled the diagnosis of a cutaneous apocrine carcinoma. Among the studies made, the increase in the serum antibody CA72.4 can be highlighted. The tumor marker was negative after the extirpation of the skin tumor and the axillary adenopathies.
Conclusion. To our best knowledge, this is the first case in which a tumor serum marker is associated with a cutaneous apocrine carcinoma, a fact that should be confirmed with further patients. Its use in the monitoring of this infrequent skin neoplasia is also noteworthy.     

Adverse events after botulinum A toxin injection for neurogenic voiding disorders

OBJECTIVES: To review the side effects of local injections of botulinum A toxin (BTX-A). METHODS: A medline search for publications about adverse events after injection of BTX-A for lower urinary tract dysfunctions. RESULTS: We found four publications that report generalised side effects after BTX-A injection for detrusor overactivity (two) and detrusor-sphincter dyssynergia (two). The causes of generalised adverse events are not clear, but spread outside the target organ and into the systemic circulation may contribute. The dose used, the injection volume and the injection technique can all play a role. CONCLUSION: Generalised side effects after BTX-A injection for voiding disorders are rare but they can be very disabling for spinal cord-injured patients. Although no long-term side effects are reported so far, urologists should be aware that these effects of BTX-A injections are unknown.     

Multiple Eccrine Hidrocystomas: A New Therapeutic Option With Botulinum Toxin

BACKGROUND: Multiple eccrine hidrocystomas are benign cystic lesions that are associated with a chronic course and seasonal variability. Even though in the literature it is presented as a very infrequent pathology, we think this is more a lack of knowledge of the existence of said pathology and the fact that patients confuse it with comedo. OBJECTIVE: To treat multiple eccrine hidrocystomas of the face. RESULTS: We present a case of multiple eccrine hidrocystomas of the face in a cook man. Hidrocystoma is a benign cystic tumor of the sweat glands eccrine or apocrine. Multiple eccrine hidrocystomas are benign cystic lesions that are associated with a chronic course and seasonal variability. They appear like multiple shining small papule. Although a solitary eccrine hidrocystoma can be treated easily with surgical excision, the elimination of multiple lesions is problematic because of their number and location. CONCLUSION: The benefits of BTX-A treatment for multiple eccrine hidrocystomas include ease of application, no risk of scarring, and a good postoperative course. Because of the blockage produced by BTX-A on cholinergic terminals of the parasympathetic system that governs sweat glands secretion, it is suggested that periodic doses of BTX-A are injected in the superficial epidermis in order to treat multiple eccrine hidrocystomas.     

Topically Applied Botulinum Toxin Type A for the Treatment of Primary Axillary Hyperhidrosis: Results of a Randomized, Blinded, Vehicle-Controlled Study

OBJECTIVE The objective was to demonstrate that botulinum toxin type A (BTX-A) can be delivered to targeted skin sites with topical application for the treatment of primary axillary hyperhidrosis.
METHODS This randomized, blinded, vehicle-controlled study enrolled 12 patients with primary axillary hyperhidrosis with greater than 50 mg of sweat produced per 5 minutes. BTX-A (200 U), combined with a proprietary transport peptide molecule to bind the toxin in a noncovalent manner, was topically applied to one axilla; vehicle without BTX-A was applied to the other axilla. Rates of sweat production were measured and imaged at baseline and 4 weeks after application.
RESULTS Two patients were excluded from analyses. At 4 weeks, 10 axillae treated topically with BTX-A demonstrated a 65.3±21.5% mean reduction in sweating relative to the same-patient, vehicle-control axillae, which had a 25.3±66.2% mean reduction. The 40% difference in mean sweat reduction between groups was statistically significant ( p< .05). Quantitative image analysis of the results of the Minor's iodine starch test confirmed the reduction of sweat production in the BTX-A–treated versus the vehicle-treated axillae.
CONCLUSION Topically applied BTX-A appears to be safe and may prove to be effective for the treatment of axillary hyperhidrosis.     

Ice Minimizes Discomfort Associated with Injection of Botulinum Toxin Type A for the Treatment of Palmar and Plantar Hyperhidrosis

BACKGROUND The value of botulinum toxin type A (BTX-A) for treatment of palmar and plantar hyperhidrosis (HH) has been limited by injection pain, which in the past has generally required administration of a nerve block. We describe the successful use of ice applied to the intended injection point followed immediately by application of either ice or vibration to skin adjacent to the injection point to reduce discomfort associated with injection of BTX-A for the treatment of palmar and plantar HH.
RESULTS During needle insertion and injection of BTX-A, both the application of ice to the intended injection point followed by application of ice adjacent to the injection point (ice+ice) and the application of ice to the intended injection point followed by application of vibration adjacent to the injection point have been preferred by our patients to nerve block. These two techniques allow efficient treatment of both hands and/or both feet in a single session.
CONCLUSION By eliminating the need for nerve blocks, the techniques described here will enlarge the pool of physicians who can administer BTX-A for palmar and plantar HH, and will enlarge the pool of patients who are willing to have this treatment.     

The Therapeutic Potential of Botulinum Toxin

BACKGROUND: Botulinum toxin type A (BTX-A; commercial preparation BOTOX) is most well known for its effect on muscle contraction because of the BTX binding to the presynaptic nerve terminal, inhibiting the release of acetylcholine (ACH). The therapeutic benefit of BTX-A, however, can also be isolated to pain relief alone, suggesting that BTX-A also works through additional modes of action. OBJECTIVE: This article provides insight by an experienced physician into four different case reports. Each case demonstrates the therapeutic potential of BTX-A and the possibility of a different mechanism of action for BTX other than the inhibition of ACH release. RESULTS: Four patients, each with different symptoms such as relapsing-remitting multiple sclerosis, postherpetic neuralgia, peripheral neuropathy, and severe tingling caused by herniation of cervical vertebrae at the level of C8, were treated with BOTOX, and their symptoms were alleviated. CONCLUSIONS: The BTX-A mechanism providing pain relief is hypothesized to be something other than muscle relaxation by inhibiting the release of ACH at the neuromuscular juncture, such as inhibition of the release of substance P or the blocking of autonomic pathways, etc. This article is intended to continue to keep physicians using this substance for dermatologic indications aware of the potential unsuspected effects.     

Hitting below the belt (Bladder): Botulinum treatment of urethral and prostate disorders

Botulinum toxin type A (BTX-A) has been used to treat urethral and prostatic diseases (off-label uses). Injection of BTX-A into the external sphincter of patients with detrusor external sphincter dyssynergia has been shown to successfully lower postvoid residual volumes and detrusor pressures. Average efficacy is 3 to 4 months, but long-term effects on detrusor leak point pressures or renal function are unknown. Injection of BTX-A into the prostate has shown promising shortterm results (≤ 12 months) in improving the symptoms, postvoid residual volumes, maximal urinary flow rates, and prostate sizes in patients with benign prostatic hyperplasia. The mechanisms of action and long-term durability of this treatment modality are unknown. Evidence supporting the use of BTX-A in treating detrusor hypocontractility, pelvic floor dysfunction, postpubovaginal sling retention, urethral stricture, prostatitis, and chronic pelvic pain syndrome in men is preliminary and deserves further evaluation.     

Treatment of Phacomatosis Pigmentovascularis: A Combined Multiple Laser Approach

Background. Phacomatosis pigmentovascularis (PPV) consists of a capillary malformation with a variety of melanocytic lesions, which involve various regions of the body and are difficult to treat with conventional therapeutic tools.
Objective. We described two cases with PPV (type IIa and IIb) that were successfully treated with different lasers.
Methods. The areas involved by both melanocytic lesions and port-wine stains were treated using the Q-switched ruby laser, the Q-switched Alexandrite laser, and the flashlamp pumped pulsed-dye laser.
Results. Removal of a good portion of cutaneous and vascular lesions using combined multiple laser approach was achieved after 6 sessions in the first case under general anesthesia and after 31 sessions under local anesthesia in the second case.
Conclusion. PPV type II can be treated successfully by laser treatment. We prefer to start combined multiple laser treatment of PPV in childhood period under general anesthesia because it will reduce the number of treatment, improve the patient's quality of life, and increase the cost-effectiveness of the treatment.     

Apocrine poroma of the breast

Abstract: Poromas are sweat gland tumors classically reported to be of eccrine origin. However, it is now recognized that poromas may also be derived from apocrine glands. There are no prior reports of either type of poroma arising on the breast. We report the first case of a poroma of the breast. The lesion was localized to the areola of a 70-year-old woman and mimicked an underlying neoplasm of the breast. Because the histopathology demonstrated apparent continuity of a benign poroma with the infundibula of hair follicles, the diagnosis of apocrine poroma was made. The poroma in this case is of apocrine derivation. This report demonstrates that apocrine poromas should be considered in the clinical differential of acquired lesions on the areola, suggesting an underlying breast tumor. Apocrine poromas that are only partially biopsied may recur. Moreover, since apocrine poromas may potentially develop into apocrine porocarcinomas, analogous to eccrine poromas sometimes transforming into eccrine porocarcinomas, apocrine poromas should be completely excised.     

Asymmetrical Smiles Corrected by Botulinum Toxin Serotype A

OBJECTIVE The objective was to identify the cause of an asymmetrical smile and to ascertain whether or not it would be correctable by injections of Botulinum toxin A (BTX-A).
METHODS Five patients with asymmetrical smiles were identified and found to lower one side of their lower lip in an exaggerated fashion when smiling or laughing. After close observation, it was determined that the ipsilateral depressor labii inferioris of the lower lip was hyperkinetic and retracted that side of the lips lower than its contralateral side when smiling or laughing. Injections of low-volume and low-dose BTX-A (BOTOX, Allergan, Inc.) were placed into the depressor labii inferioris on the side where the lower lip retracted the lowest.
RESULTS All of the five patients with asymmetrical smiles presented with unilateral hyperkinetic depressor labii inferioris and responded to injections of BOTOX. Their lower lips became level and their smiles were symmetrical within 1 week of the BOTOX treatments. Their lip symmetry lasted for at least 6 months after their initial treatment. With each additional treatment, the duration of BOTOX lasted even longer, averaging approximately 7 months.
CONCLUSION BOTOX is an effective, safe, and long-lasting treatment for lower lip asymmetries caused by a hyperkinetic depressor labii inferioris.     

Recurrent Pleural Effusion and Pulmonary Metastases from a Cutaneous Apocrine Tumour of the Axilla

Sweat gland carcinomas are very rare and they are differentiated between tumours of apocrine or eccrine origin. The axilla is the most common site for apocrine gland carcinoma for its great abundance of these glands. There are no recommendations in literature regarding appropriate treatment schedules for apocrine gland carcimonas in advanced stages. We report a case of recurrent left pleural effusion in a 76-year old man with metastatic cutaneous apocrine tumour of the right axilla. We describe the clinical and histological features, with management options and a review of the relevant literature on apocrine gland carcinoma.     

Recurrent pleural effusion and pulmonary metastases from a cutaneous apocrine tumour of the axilla

Sweat gland carcinomas are very rare and they are differentiated between tumours of apocrine or eccrine origin. The axilla is the most common site for apocrine gland carcinoma for its great abundance of these glands. There are no recommendations in literature regarding appropriate treatment schedules for apocrine gland carcimonas in advanced stages. We report a case of recurrent left pleural effusion in a 76-year old man with metastatic cutaneous apocrine tumour of the right axilla. We describe the clinical and histological features, with management options and a review of the relevant literature on apocrine gland carcinoma.     

What Is the Role of Additional Pharmacotherapy and Neuromodulation in Patients with Marginal Benefit from Botulinum Toxin Injection?

Purpose of Review

Third-line therapies for patients with overactive bladder (OAB) can improve symptoms for those who have failed conservative therapies. Options include percutaneous tibial nerve stimulation (PTNS), cystoscopic injection of onabotulinumtoxinA (BTX-A), and sacral neuromodulation (SNM). This paper aims to review the current literature on the treatment of patients with idiopathic OAB who have undergone BTX-A injections and have not responded or have undesirable side effects from the therapy.

Recent Findings

There are no randomized control trials examining the role of concurrent medical therapy and BTX-A; rather, there are observational studies in the neurogenic population. Furthermore, there are two observational studies on the role of SNM in BTX-A refractory idiopathic OAB patients demonstrating its safety and efficacy.

Summary

There are many options available to the patient who fails BTX-A. Further research in this specific patient population is necessary to determine why patients have suboptimal responses and to delineate the next step in treatment.

     

Treatment of Hypertrophic Scars With Intralesional Botulinum Toxin Type A Injections: A Preliminary Report

Background  Hypertrophic scar is the abnormal appearance of wound healing that usually causes major physical, psychological, and cosmetic problems. Treatment of the hypertrophic scar still is a dilemma due to the lack of effective and excellent methods and agents. Recent reports show that botulinum toxin type A (BTX-A) improves wound healing. Therefore, the authors hypothesized that BTX-A may be favorable for the improvement of hypertrophic scars. Methods  A total of 19 patients were randomly assigned to a prospective clinical study. At 1-month intervals, BTX-A (2.5 U per cubic centimeter of lesion) was injected in these patients for a total of 3 months. All the patients were followed up for at least half a year. Therapeutic satisfaction was recorded, and the lesions were assessed for erythema, itching sensation, and pliability. Results  The study was completed by 19 patients. At the half-year follow-up visits, all the patients showed acceptable improvement, and the rate of therapeutic satisfaction was very high. The erythema score, itching sensation score, and pliability score after the BTX-A injection all were significantly lower than before the BTX-A injection. The differences all were statistically significant (P < 0.01). Conclusion  For the treatment of hypertrophic scars, doctors and patients both found BTX-A acceptable because of its better therapeutic results. Its effect of eliminating or decreasing hypertrophic scars was promising. Zhibo Xiao and Fengmin Zhang are the primary authors of this article.     

Metallic Taste: An Unusual Reaction to Botulinum Toxin A

BACKGROUND: Botulinum neurotoxin formulations are safe and effective agents for the treatment of facial rhytides. OBJECTIVES: A patient is described who complained of metallic taste after each treatment with botulinum toxin A (BTX-A). RESULTS: The sensation of metallic taste diminished after successive treatments with BTX-A, despite adequate dosing for cosmetic purposes. CONCLUSION: Metallic taste is associated with the use of numerous medications; however, the pathogenesis remains unclear. Alteration in zinc metabolism, which may occur with BTX-A administration, has been suggested as a possible mechanism. Although this is the first known report of dysgeusia after BTX-A, physicians and patients may be reassured that the taste alteration was self-limited and was not significantly problematic for the patient in our case.     

Botulinum A Toxin (BOTOX) in the Lower Eyelid: Dose-Finding Study

BACKGROUND: Botulinum toxin type A (BTX-A, BOTOX) is an excellent therapeutic option for hyperkinetic facial lines. It improves wrinkles by relaxing the muscles of facial expression, which underlie the rhytids. Periocular wrinkles such as lateral orbital rhytids respond well to treatment. BOTOX can be used in the lower eyelid to improve wrinkles and widen the eye. OBJECTIVE: To determine whether there is additional benefit in using more than 2 U of BTX-A to improve infraorbital wrinkles and widen the eye. METHODS: Nineteen women had BTX-A injected into the orbicularis oculi muscle. Eleven women had 4 U injected into the lower eyelid bilaterally, 3 mm below the ciliary margin, and 12 U of BTX-A injected into one lateral orbital (crow's feet) area. Eight patients had 8 U injected bilaterally into the lower eyelid and 12 U placed unilaterally into the crow's feet. Physicians and patients independently evaluated the degree of improvement (grade 3=dramatic improvement, grade 2=moderate improvement, grade 1=mild improvement, and grade 0=no improvement). Single investigator analysis was used to measure, in actual millimeters, the amount of increase in palpebral aperture. Side effects were noted. RESULTS: Improvement was noted in lower eyelid wrinkles by both physicians and patients at both dose groups. When only the lower lid was injected, patients reported an improvement of 1.18 with 4 U and a grade of 1.63 with 8 U. When both the lower eyelid the lateral orbital area were treated, an improvement of 1.73 was reported with 4 U and a grade of 2.25 reported with 8 U in the lower eyelid. Physician evaluations had grades of 1.85 for 4 U alone and 1.85 with 8 U alone. Grades of 2.35 and 2.25 were obtained for 4 U plus 12 U and 8 U plus 12 U, respectively. An increase in palpebral aperture (IPA) occurred in all subjects. Subjects who received 4 U in the lower eyelid alone had a 1.8-mm IPA at rest and a 2.6-mm increase at full smile. Subjects who received 8 U of BTX-A alone in the lower lid had an IPA of 2.2 mm at rest and 2.9 mm at full smile. Eyes treated with 12 U in the bilateral orbital area plus 4 U in the lower eyelid had an IPA of 2.2 at rest and 4.5 mm at full smile. Those treated with 8 U in the lower lid plus the crow's feet had an IPA of 1.5 at rest and 4.0 at full smile. Side effects increased with dosage, with eight of eight subjects in the 8-U dose groups reporting bothersome side effects such as lower eyelid edema and incomplete sphincter function. CONCLUSION: A dose-response curve is seen with increasing doses of BTX-A used in the lower eyelid. Treatment of the lateral orbital area in combination with the lower lid produces a synergistic response at lower doses, but at higher doses, a plateau effect is suggested. Although increasing doses of BTX-A increases eye widening, unattractive results and side effects are seen at higher doses. The authors recommend that lower 2- or 4-U doses of BTX-A be used in the lower eyelid and specifically discuss techniques.