Effect of botulinum toxin concentration on reduction in sweating: a randomized, double-blind study.

Dose-response studies of botulinum toxin for reduction of sweating are sparse in the literature. The aim of this study was to determine the most appropriate concentrations of Botox®, Dysport®, Xeomin® and NeuroBloc®, respectively, in order to achieve the greatest reduction in sweating, thus reducing the costs and increasing the safety of treatment. Four concentrations of each product were investigated. Intradermal injections of all products and concentrations were applied to the backs of 20 consenting subjects, in a randomized, double-blind manner. Areas of anhidrotic and hypohidrotic skin were measured with an iodine-starch test after 4, 8 and 12 weeks, respectively. Optimal concentrations were found to be 25 U/ml for Botox and Xeomin, approximately 100 U/ml for Dysport, and 50 U/ml for NeuroBloc. When comparing the mean anhidrotic area per unit for 100 U/ml of each product, the calculated dose conversion ratios were 1:1.6:1.2:1.3 (Botox:Dysport:Xeomin:NeuroBloc). If, instead, the optimal concentration for each product was compared, the dose conversion ratios were 1:4.8:1.3:2.2. Thus, it is crucial to consider botulinum toxin concentration in a treatment regimen.

Bilateral forearm intravenous regional anesthesia with prilocaine for botulinum toxin treatment of palmar hyperhidrosis.

BACKGROUND: Treatment of palmar hyperhidrosis with botulinum toxin (BTX) requires effective anesthesia, but previous methods have not provided enough pain relief or have resulted in a prolonged impaired hand function. OBJECTIVE: This is a study of bilateral forearm intravenous regional anesthesia using prilocaine for BTX treatment of palmar hyperhidrosis. METHODS: In all, 166 patients (100 female and 66 male) were treated bilaterally with intracutaneous BTX type A injections using intravenous regional anesthesia with prilocaine (5 mg/mL). In a subgroup of patients, forearm nerves were studied with neurophysiologic methods and blood concentrations of prilocaine were measured. Pain evaluation with a visual analog scale was accompanied with a questionnaire about the treatment. RESULTS: In all, 95% of the patients answering the questionnaire (response rate 89%) were satisfied with the anesthetic effect. No serious adverse events occurred. There was a fast recovery of motor function (in median 6 minutes) and sensory function (in median 20 minutes). No subclinical signs of sensory nerve damage were found. LIMITATIONS: Recall and reporting bias are potential sources of limitations in this study. CONCLUSION: Bilateral forearm intravenous regional anesthesia provides an effective and well-tolerated anesthesia during BTX treatment of palmar hyperhidrosis.

[Hyperhidrosis is a silent handicap]. / Hyperhidrose er et tavst handicap.

Hyperhidrosis affects 2.8% of the population and has severe negative influence on life quality. The disease is represented in many specialties but can unfortunately be incorrectly treated or not treated at all. Primary hyperhidrosis is the most common form. Secondary hyperhidrosis is most often excluded by a few anamnestic data. Botulinum toxin and anticholinergics are adequate treatment options when aluminium chloride is insufficient. This article describes the disease from the physician's as well as the patient's perspective. Furthermore, examination procedures and treatment procedures are presented.

Rituximab in paediatric onset multiple sclerosis: a case series.

Paediatric onset multiple sclerosis (POMS) is characterized by high inflammatory activity. No disease modifying treatment has been approved for POMS. The objective of this report was to report the use of rituximab, a B cell depleting monoclonal anti-CD20-antibody, in POMS. This is a retrospective case series at four specialized MS centres in Sweden. Participants were identified through the Swedish MS-registry and our own patient stocks. Data were collected through medical charts review. We identified 14 POMS patients treated with i.v. rituximab 500-1000 mg every 6th to 12th months. Median age at disease onset was 14.7 years, median age at rituximab treatment initiation was 16.5 years, and median treatment duration was 23.6 months. No relapses were reported, and the EDSS scores remained stable or decreased in 13 of 14 cases during rituximab treatment. Beyond 6 months from initiating rituximab treatment, only one new lesion was detected on MRI. No serious AEs were reported. The drug survival was 86%. Our data indicate that rituximab treatment is safe, effective and well tolerated in children with MS. Nine POMS cases treated with rituximab have previously been published. They had higher disease activity pre-rituximab, but similar safety and efficacy outcomes after treatment. An RCT of rituximab in POMS is warranted.

Sweat gland morphology and periglandular innervation in essential palmar hyperhidrosis before and after treatment with intradermal botulinum toxin.

BACKGROUND: Intradermal botulinum toxin (Btx) produces long-lasting relief of focal hyperhidrosis, but its mechanism of action is poorly understood. OBJECTIVE: To study the effect of Btx A on the size and innervation of sweat glands in patients with palmar hyperhidrosis. METHODS: Palmar skin biopsy was performed in 26 hyperhidrotic patients before scheduled Btx treatment and in 11 controls. Twelve of the patients also underwent biopsy 1 to 6 months after the Btx injections. Sweat gland morphology was investigated by light microscopy; the cross-sectional area of the secretory tubule and its lumen was measured by image analysis. Immunofluorescence (IF) with antibodies to the neural markers protein gene product 9.5 (PGP 9.5) and growth-associated protein 43 (GAP 43), and to vasoactive intestinal peptide (VIP) and calcitonin gene-related peptide (CGRP), was used to analyze the periglandular innervation. RESULTS: The gross morphology of the sweat glands was similar in patients and controls, with no significant differences in tubular and luminal areas between the groups. After Btx treatment, the tubular dimensions remained unchanged, but the lumen tended to be smaller ( P = .07). Around the glands, increased GAP 43 staining indicating sprouting was seen within 3 months after Btx treatment ( P = .016); whereas the PGP 9.5 staining was decreased in most specimens ( P = .09) indicating lack of functional nerve growth. No change in VIP or CGRP immunoreactivity was observed. CONCLUSIONS: The sweat glands appear structurally normal in hyperhidrotic patients before Btx therapy, whereas after therapy the luminal area of the gland is frequently diminished. The IF data GAP 43/PGP 9.5 suggest that Btx therapy induces long-standing functional denervation of the sweat glands, which might explain its anti-transpiratory efficacy.

Clinical experience of dose conversion ratios between 2 botulinum toxin products in the treatment of cervical dystonia.

OBJECTIVES: The units of different botulinum toxin products are not identical, and the dose equivalence has been debated for several years. In the year 2000, our clinic changed the recommended botulinum toxin product from Botox to Dysport for the treatment of cervical dystonia. Based on published reports, where dose conversion ratios from 1:1 to 1:6 (Botox:Dysport) had been used, and our own clinical experience, the dose conversion ratio was set to 1:2. The objective of this study was to retrospectively monitor the used doses of each product and the subsequent clinical effect. METHODS: A retrospective study, using casebook notes from 75 patients, was done to investigate treatment doses, subjective clinical effect, and the appearance of adverse events. RESULTS: The median dose conversion ratio that had been used at the product switch was 1:2.3 (Botox:Dysport). After clinical adjustment, the ratio was 1:2.1 at the next 3 treatments. There was a tendency for a more effective treatment and more adverse events after the product switch. A follow-up was performed 6.5 years later using casebook notes from 53 of the same patients. By this time, the doses had been reduced, and the median dose conversion ratio had decreased to 1:1.7 (Botox:Dysport). The adverse events reported at this point were fewer for the patients treated. CONCLUSIONS: In this study, the most appropriate dose conversion ratio to use when switching from Botox to Dysport was 1:1.7.

Dose equivalence of two commercial preparations of botulinum neurotoxin type A: time for a reassessment?

BACKGROUND: The units of different preparations of botulinum neurotoxin type A (BoNT-A) have different potencies, and dosing recommendations for each product are not interchangeable. Historically, there has been debate concerning the dose-equivalence ratio that should be used in clinical practice. METHODS: Published evidence was considered to establish an appropriate dose-conversion ratio for the two main commercially available preparations of BoNT-A--Dysport (Dp) and Botox (Bx). RESULTS: Four key areas of evidence were identified: nonclinical and preclinical studies; studies exploring the diffusion characteristics and effects of complexing proteins; comparative experimental data from human studies; and clinical studies. Nonclinical data indicate that the principal reasons for differences in unit potency between the two products are dilution artefacts in the mouse assay. Use of saline as a diluent, at high dilutions, results in significant loss of potency in the Bx assay, whereas use of gelatin phosphate buffer in the Dp assay procedure protects the toxin during dilution. The published data on mouse assays show a Dp : Bx unit ratio range of 2.3-2.5 : 1 in saline and 1.8-3.2 : 1 in gelatin phosphate buffer. Data indicate that complexing proteins or size of the complex, which is highly pH sensitive, play no role in toxin diffusion and that Dp and Bx have similar diffusion characteristics when used at comparable doses. Randomized, controlled clinical studies indicate that 3 : 1 is more appropriate than 4 : 1, but the two products are not equivalent at this ratio. Comparative human experimental studies using the extensor digitorum brevis test, facial lines and anhidrotic action halo tests support dose-conversion ratios less than 3 : 1. LIMITATIONS: Data comparing dose equivalence ratios from the non-clinical setting should be extrapolated into the clinical setting with some caution. CONCLUSIONS: Dose-conversion ratios between Dp and Bx of 4 : 1 and greater are not supported by the recent literature.

Equipotent concentrations of Botox and Dysport in the treatment of palmar hyperhidrosis.

There are indications that the dilution of botulinum toxin affects dose-response. This must be considered when comparing different products. The aim of this study was to estimate a concentration of Dysport in physiological saline that is approximately equivalent to Botox 100 U/ml with respect to anhidrotic and muscular effect. Thirty-six patients with primary palmar hyperhidrosis were treated with multiple intradermal injections of 0.02 ml botulinum toxin. Botox(R) was injected in one hand and Dysport in the other in a random order. The concentrations of Dysport were 200 U/ml (n=18), 150 U/ml (n=11) and 100 U/ml (n=7). Muscular effect was measured as the reduction in compound muscle action potential in 3 muscles in the hand and anhidrotic effect was indicated by an iodine-starch test 4 weeks after treatment. Dysport at 200 U/ml was more potent than Botox at 100 U/ml with regard to both anhidrotic and muscular effect. The equipotent concentration of Dysport, compared with Botox 100 U/ml, was found to be in the range 100-150 U/ml.

Anhidrotic effect of intradermal injections of botulinum toxin: a comparison of different products and concentrations.

Botulinum toxin is used in various fields of medicine, including in the treatment of hyperhidrosis. Three products containing botulinum toxin are commercially available in Sweden; Botox, Dysport and Neurobloc. In the literature dose-response has varied with respect to these 3 products. We hypothesized that the dilution level of botulinum toxin is of importance for the effect and we therefore investigated anhidrosis after intradermal injections of each product in 3 different concentrations. Nine healthy subjects received 0.1 ml injections in the back. The anhidrotic areas were identified by an iodine-starch test after 3 weeks. When the 3 products were diluted to 100 U/ml level the achieved mean anhidrotic areas were approximately the same. This is in strong contrast with the large dose conversion factors suggested for intramuscular injections of the products. Furthermore, the lowest used concentrations for Botox(R) (25 U/ml) and Neurobloc (100 U/ml) led to the largest anhidrotic mean area per unit, respectively. The optimal concentration in this study was 25 U/ml for Botox, 100 U/ml for Dysport and 100 U/ml for Neurobloc, but for Botox and Neurobloc the optimal concentrations may be even lower.

Treatment of dyshidrotic hand dermatitis with intradermal botulinum toxin.

BACKGROUND: Botulinum toxin (Btx A) has recently been used in the treatment of focal hyperhidrosis. Hyperhidrosis is also an aggravating factor in nearly 40% of patients with dyshidrotic hand eczema. OBJECTIVE: The objective of this study was to evaluate the effect of intradermal injections of Btx A on dermatitis in patients with vesicular hand dermatitis. METHODS: Ten patients with vesicular dermatitis were treated on one hand with intradermal Btx A (mean, 162 U BOTOX, Allergan Pharmaceuticals, Irvine, Calif) with the untreated side as a control. RESULTS: Self-assessment at follow-up 5 to 6 weeks after injection on a 5-point scale (none, slight, moderate, good, or very good effect) showed that 7 of 10 patients experienced good or very good effect. A decrease in itching was shown with a visual linear analogue scale (VAS) for itching, with mean 39% on the treated side compared with an increase by 52% on the untreated side. These findings were supported by the evaluation of clinical signs. Six of 7 patients who experienced good or very good effect also had aggravating hand sweating or worsening during the summer. CONCLUSION: Btx A can be a valuable alternative for patients with treatment-refractory hand eczema of the vesicular type, especially with hyperhidrosis or worsening during the summer.