Helga Konrad

Managing adverse events associated with botulinum toxin type A: A focus on cosmetic procedures

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.

Treatment of common warts and actinic keratoses by Er:YAG laser

BACKGROUND AND OBJECTIVES: The use of ablative lasers in the treatment of common warts and precancerous actinic keratoses has been reported in the literature, showing variable response rates and relapse rates. The erbium:YAG laser (Er:YAG) with a wavelength of 2.94 w m allows precise ablation avoiding strong inflammation. The authors have evaluated the potential benefits of Er:YAG laser treatment for difficult-to-treat warts and actinic keratoses. PATIENTS AND METHODS: A total of 69 patients with difficult-to-treat warts (periungual or plantar) with a mean age of 30.1 - 16.1 years (range 11-58 years), and 29 patients with actinic keratoses with a mean age of 73.5 - 9.7 years (range 58-90 years) were treated by Er:YAG laser. Ablative therapy was performed with a spot size of 3 mm, a frequency between 8 Hz and 15 Hz, and a fluence of 5.7-11.3 J cm -2 (warts) or 5.7-7.1 J cm -2 (actinic keratoses). RESULTS: After a single laser treatment a complete response (CR) was observed in 50 patients with warts (72.5%). Plantar warts were more resistant (13.5% non-responder) compared with periungual warts (5.9% non-responder). Twelve patients with a CR showed a relapse within 3 months after treatment (24.0%). All but one suffered from plantar warts. Twenty-six patients with actinic keratoses showed a CR after a single laser treatment, and in three patients a partial response (PR) was achieved. None of the patients treated with Er:YAG laser developed pigment changes, wound infections or scarring. CONCLUSION: Treatment of common epithelial lesions such as common warts or actinic keratoses by Er:YAG laser is safe and effective. In patients with plantar warts, however, a significant rate of relapse may occur, requiring additional therapy.

Intracutaneous botulinum toxin A versus ablative therapy of Hailey-Hailey disease--a case report.

BACKGROUND: Hailey-Hailey disease is an autosomal-dominant blistering disease affecting the intertriginous skin. Dermabrasion and ablative laser treatment are known to be curative. Sweating is a common aggravating factor. Botulinum toxin A (BTXA) has been shown to inhibit sudoriferic nerves. OBJECTIVE: To evaluate whether a treatment with BTXA induces remissions and can compete with ablative therapy. To compare dermabrasion with erbium:YAG laser therapy. METHOD: Case report with side-by-side comparison. We used intracutaneous BTXA on both sides of the submammary region. Four days later a limited area of 25 cm 2 on each side was treated with either dermabrasion or erbium:YAG laser. The follow-up was 12 months. RESULTS: Wound healing was complete within 7 days after erbium:YAG laser and two weeks after dermabrasion. Areas treated with BTXA alone also showed complete remission within two weeks. During a follow-up, no relapse occurred with either treatment. CONCLUSION: BTXA is capable of inducing remissions of Hailey-Hailey disease without abrasion for at least 12 months. Among ablative treatments, erbium: YAG laser therapy leads to a more rapid wound closure than dermabrasion, with both causing complete remissions.

Botulinum toxin A for focal hyperhidrosis in leg amputees: a case report.

Sir, Among the side-effects arising with a prosthesis, ®tting problems and dermatological complaints are the most frequent. The importance of prevention or early recognition of skin problems cannot be overemphasized to avoid bed rest and other handicaps (1). One major problem in leg amputees is stump hyperhidrosis. The use of silicone pads and other rather occlusive materials in prostheses aggravates hyperhidrosis, leading to lubrication. Whereas occlusion alone can cause hydration of the stratum corneum, the combination of lubrication with occlusion initiates prolonged disturbance of the skins barrier function (2). Hyperhidrosis is linked to discomfort and a number of skin complaints including malodour, folliculitis and other bacterial and mycological skin disease, and the development of irritant and allergic contact dermatitis (1). Several attempts have been made to treat hyperhidrosis including topical astringent agents and tap water iontophoresis (3). Recently, botulinum toxin A (BTXA) has been used to treat focal hyperhidrosis (4, 5). BTXA is a zinc endopeptidase. The toxin is internalized by endocytosis at the axon terminal and becomes fully activated by disulphide reduction once inside the cell. BTXA targets SNAP-25 involved in acetylcholine release (6). We report a patient with leg amputation and hyperhidrosis of the stump treated successfully with BTXA for stump hyperhidrosis. A 58-year-old man, with a lower leg amputation due to osteomyelitis in 1962, was referred to the Department of Dermatology because of suspected contact dermatitis. He suffered from diabetes mellitus, stump hyperhidrosis, and nummular microbial eczema. On examination we found a lower leg amputation stump with a suction stocking prosthesis. The itching, malodorous, exudating, hyperhidrotic skin showed erythematous scaling lesions and mild distal veruccous hyperplasia. Laboratory investigations, including differential blood count, creatinine, urea, bilirubin, serum enzymes, urine analysis, total IgE, and protein electrophoresis, were normal. Several swabs were taken from the exudating skin lesions. A mixed bacterial culture was found including aerobic (Acinetobacter iwof®, Corynebacterium spp., Sphingomonas paucimobilis and saprophytic staphylococci) and anaerobic species (Camphylobacter rectus, Propionibacteria, Peptostreptococci and Bacteroides spp.). Patch testing was performed according to the German Contact Dermatitis Research Group (7). No type-IV sensitization was found against the most common allergens of the standard test, textile colours, rubbers, topical ointments and conservatives, and materials of his own prosthesis. We performed topical treatment of the microbial eczema including a povidone-iod based disinfectant and topical corticosteroid creme (initially amcinonide; later on prednicarbat). Eczema and pruritus disappeared. After informed consent we treated his stump hyperhidrosis with BTXA. Hyperhidrotic areas were identi®ed by Minors iodineÐstarch test (8). As shown in Fig. 1, they were found on both the distal and the lateral part of the stump. For treatment, 100 U of BTXA (Botox; Allergan, Irvine, CA, USA; distributed by Merz Pharma Germany) were diluted with 4.0 ml 0.9% sterile physiological saline without preservative. The toxin was injected in amounts of 0.05 ± 0.1 ml (5 ± 10 U) strictly intracutaneous using a 30 gauge needle. Analgesic therapy was not necessary. The effect was evaluated by Minors iodineÐstarch test 3 days later (Fig. 2). The patient had a consultation 3 months later. He was still satis®ed with the anhidrotic effect. There was no relapse of the microbial eczema. The development of functional and aesthetic leg prostheses is a great advantage for amputees. The ongoing use of the prosthesis, however, may account for some discomfort and skin problems. Sweating inside the socket is annoying and Fig. 1. Identi®cation of hyperhidrotic areas after Minors sweat test.

Botulinum toxin in dermatology – beyond wrinkles and sweat

Botulinum toxin (BTX) types A and B have been used with success in cosmetic dermatology and hyperhidrosis treatment.

Optical tomography of human skin with subcellular spatial and picosecond time resolution using intense near infrared femtosecond laser pulses

We describe the novel high resolution imaging tool DermaInspect 100 for non-invasive diagnosis of dermatological disorders based on multiphoton autofluorescence imaging (MAI)and second harmonic generation. Femtosecond laser pulses in the spectral range of 750 nm to 850 nm have been used to image in vitro and in vivo human skin with subcellular spatial and picosecond temporal resolution. The non-linear induced autofluorescence originates mainly from naturally endogenous fluorophores/protein structures like NAD(P)H, flavins, keratin, collagen, elastin, porphyrins and melanin. Second harmonic generation was observed in the stratum corneum and in the dermis. The system with a wavelength-tunable compact 80 MHz Ti:sapphire laser, a scan module with galvo scan mirrors, piezoelectric objective positioner, fast photon detector and time-resolved single photon counting unit was used to perform optical sectioning and 3D autofluorescence lifetime imaging (t-mapping). In addition, a modified femtosecond laser scanning microscope was involved in autofluorescence measurements. Tissues of patients with psoriasis, nevi, dermatitis, basalioma and melanoma have been investigated. Individual cells and skin structures could be clearly visualized. Intracellular components and connective tissue structures could be further characterized by tuning the excitation wavelength in the range of 750 nm to 850 nm and by calculation of mean fluorescence lifetimes per pixel and of particular regions of interest. The novel non-invasive imaging system provides 4D (x,y,z,t) optical biopsies with subcellular resolution and offers the possibility to introduce a further optical diagnostic method in dermatology.

Response of spider leg veins to pulsed diode laser (810 nm): a clinical, histological and remission spectroscopy study.

BACKGROUND: Spider leg veins are common. Their treatment with laser or intensed light therapy shows generally variable success rates and often adverse side effects such as hyper‐ or hypopigmentation. This study was performed to investigate whether pulsed diode laser (810 nm) treatment is effective and safe. METHODS: Thirty‐five female patients with spider leg veins were included in this prospective trial. They were treated twice with a pulsed diode laser (810 nm; spot size 12 mm, frequency 2–4 Hz, pulse width 60 msec, fluence 80–100 Jcm−2). Laser therapy was performed on day 0 and day 14. Clinical assessments were carried out before and immediately after the first laser therapy, after 2 weeks, 8 weeks, and one year. Skin biopsies were taken before and immediately after the first laser treatment, and after 10 weeks. Contact‐free remittance spectroscopy was performed before laser treatment, immediately after the first treatment, after 2 weeks and 8 weeks. RESULTS: After the first treatment 15 patients showed a complete disappearance (CR) of spider leg veins; in the remaining 20 patients a remarkable improvement (RI) was noted (n=35). After six months of follow‐up CR was seen in 6 patients, RI in 6, a stable situation in 9, and scar formation in 1 patient (n=21). The effect was almost completely stable during one year of follow‐up. The examination of histological specimens before and after laser treatment showed no cellular inflammatory reaction. The mean vascular area was significantly reduced after the first (p<0.05) and after the second (p<0.05) laser treatment. Spectral analysis showed a marked decrease of peaks for oxygenized haemoglobin immediately after laser treatment and during the follow‐up. Safety profile was excellent without purpuric reaction or pigmentary changes. Mild scarring was observed in two patients at the end of follow‐up. CONCLUSIONS: Pulsed diode laser therapy (810 nm) is an effective and safe treatment option for spider leg veins. The effects can be seen immediately. Objective monitoring by non‐invasive remission spectroscopy and histology of biopsy specimens demonstrates selectivity of the laser action.

Recessive Epidermolysis Bullosa Dystrophicans (Hallopeau-Siemens)—Improvement of Wound Healing by Autologous Epidermal Grafts on an Esterified Hyaluronic Acid Membrane

Epidermolysis bullosa dystropicans of the Hallopeau‐Siemens type (HS‐EBD) is an autosomal‐recessive blistering disease. Skin fragility due to mutations in structural proteins is responsible for further development of chronic and painful wounds, skin infections and sepsis. There is no causative treatment available. We present a case report with HS‐EBD and longstanding painful wounds treated with autologous keratinocytes on an esterified hyaluronic acid membrane. Two out of three wounds treated showed a complete take of the graft. They improved markedly with a stable result over 12 months until now. Even autologous keratinocyte grafting may have a beneficial effect on chronic wounds in HS‐EBD despite the fact that the genetic defects are unchanged.

Vis-NIR spectroscopic and clinical evaluations of the response of spider leg veins to a high-powered, pulsed diode laser (810 nm) therapy

Spider leg veins represent an important aesthetic problem. This clinical study was performed to investigate the pulsed near-infrared diode laser (810 nm) treatment of spider leg veins. 35 female patients were enrolled in this study and treated twice with laser densities of energy (fluence) between 60 - 100 J/cm2 and a spot size of 50 mm2. Histological examinations were performed to investigate morphological and functional effects. Spectroscopic investigations were used as a non-invasive evaluation tool. After the first laser treatment 15 patients showed a complete disappearance (CR); in the remaining 20 patients a remarkable improvement (RI) was seen (N=35). After six months of follow-up CR was noted in 6 patients, RI in 6, a stable situation in 9, and scar formation in one patient (N=21). The histological examination before and after laser treatment showed no cellular inflammatory reactions. The mean vascular areas were significantly reduced after the laser treatments. Vis-NIR spectroscopic investigations showed almost an immediate occurrence of the haemoglobin double peak and a prompt decrease of the visible remittance after laser treatment of the skin. Pulsed diode laser therapy is a safe and effective option for the treatment of spider leg veins. Objective in vivo- monitoring by remission spectroscopy and the histology of biopsy specimens show the immediate and long-term laser effects of the irradiated skin in detail.