An open, multicentre, randomized clinical study in patients with bullous pemphigoid comparing methylprednisolone and azathioprine with methylprednisolone and dapsone.

BACKGROUND: Current treatment of bullous pemphigoid (BP) is based on the long-term use of topical and/or systemic corticosteroids, which are associated with a high rate of adverse events and increased mortality. OBJECTIVES: To study the corticosteroid-sparing potential of azathioprine and dapsone. METHODS: This was a prospective, multicentre, randomized, nonblinded clinical trial that compared the efficacy and safety of two parallel groups of patients with BP treated with oral methylprednisolone 0·5 mg kg-1 per day in combination with either azathioprine 1·5-2·5 mg kg-1 per day or dapsone 1·5 mg kg-1 per day. Nine German and Austrian departments of dermatology included 54 patients based on clinical lesions, positive direct immunofluorescence (IF) microscopy and detection of serum autoantibodies by indirect IF microscopy, immunoblotting or enzyme-linked immunosorbent assay. The primary end point was the time until complete tapering of methylprednisolone, and the most important secondary end point was the cumulative corticosteroid dose. RESULTS: In eight patients (five azathioprine, three dapsone), methylprednisolone could be discontinued after a median time of 251 days in the azathioprine group and 81 days in the dapsone group. The median cumulative corticosteroid dose was 2·65 g for azathioprine compared with 1·92 g for dapsone (P = 0·06). The median numbers of days when corticosteroids were applied were 148 and 51, respectively (P = 0·24). No significant difference in the number of adverse events was seen between the treatment arms. Four patients (8%) died within the observation period of 12 months. CONCLUSIONS: Due to the lower than intended number of patients, the results of the primary and secondary end points were not or only barely significant. Dapsone appeared to have a moderately higher corticosteroid-sparing potential than azathioprine. The combination regimen of either drug with oral methylprednisolone is associated with a relatively low 1-year mortality in this vulnerable patient population.

The impact of adverse reactions to injectable filler substances on quality of life: results from the Berlin Injectable Filler Safety (IFS) - study.

BACKGROUND: Injectable filler substances are commonly used in aesthetic medicine. Adverse reactions are rare, but may cause severe impact on quality of life (QoL). To the best of our knowledge, data on the impact of adverse reactions caused by injectable filler substances on QoL is missing. OBJECTIVE: To evaluate the impact of adverse filler reactions on the QoL. MATERIAL AND METHODS: The Injectable Filler Safety (IFS) - study is a partially population-based registry for adverse reactions due to injectable filler substances. In 2008, the Dermatology Life Quality Index (DLQI) questionnaire was added to the questionnaires of the IFS study. For this analysis, only patients with a completed DLQI were included in the analysis. RESULTS: One hundred and four patients of the IFS study were analysed. A total of 88.5% were female with an average age of 49.2 years. Here, 50.0% were treated with biodegradable and 40.4% with permanent fillers. The most common adverse reactions were nodule formation and hardening. Most patients experienced mild to moderate adverse reactions. Impact on QoL was moderate with an average of 8.9 (±8.4 SD) in patients with adverse reactions to biodegradable and 10.5 (±9.4 SD) to permanent products. However, 24.0% and 13.4% showed a large or a very large impact on QoL. CONCLUSION: Adverse reactions to injectable filler products can have a considerable impact on the QoL, comparable to severe chronic inflammatory skin diseases such as psoriasis.

[The satisfied patient in aesthetic dermatology. Consensus work on patient satisfaction in botulinum toxin A treatment]. / Der zufriedene Patient in der ästhetischen Dermatologie. Konsensusarbeit zur Patientenzufriedenheit in der Behandlung mit Botulinumtoxin A.

Patient satisfaction is an important factor for successful therapy. Many consensus reports have been published regarding correct treatment with botulinum toxin A (BTX-A). However, the focus of most of these publications has been on technical aspects and the important topic of patient satisfaction was often only one aspect among others. The Swiss Group of Esthetic Dermatology and Skincare (SGEDS) pursued these questions in a two-day consensus meeting. Patients of aesthetic dermatology are healthy and therefore place higher demands in contrast to ill patients of medical dermatology. This demands a great deal of the physician, the practice staff and the conditions in the practice to accommodate the special requirements of aesthetic clients. Informative consultation and patient education are of major importance; this also holds true for clinical performance and care before, during and after treatment with BTX-A. This publication aims at finding ways to gain greater patient satisfaction in daily practice.

Reduction of unwanted submental fat with ATX-101 (deoxycholic acid), an adipocytolytic injectable treatment: results from a phase III, randomized, placebo-controlled study.

BACKGROUND: Unwanted submental fat (SMF) is aesthetically unappealing, but methods of reduction are either invasive or lack evidence for their use. An injectable approach with ATX-101 (deoxycholic acid) is under investigation. OBJECTIVES: To evaluate the efficacy and safety of ATX-101 for the reduction of unwanted SMF. METHODS: In this double-blind, placebo-controlled, phase III study, 363 patients with moderate/severe SMF were randomized to receive ATX-101 (1 or 2 mg cm(-2) ) or placebo injections into their SMF at up to four treatment sessions ~28 days apart, with a 12-week follow-up. The co-primary efficacy endpoints were the proportions of treatment responders [patients with ≥ 1-point improvement in SMF on the 5-point Clinician-Reported Submental Fat Rating Scale (CR-SMFRS)] and patients satisfied with their face and chin appearance on the Subject Self-Rating Scale (SSRS). Secondary endpoints included skin laxity, calliper measurements and patient-reported outcomes. Adverse events were monitored. RESULTS: Significantly more ATX-101 recipients met the primary endpoint criteria vs. placebo: on the clinician scale, 59·2% and 65·3% of patients treated with ATX-101 1 and 2 mg cm(-2) , respectively, were treatment responders vs. 23·0% for placebo (CR-SMFRS; P < 0·001); on the patient scale, 53·3% and 66·1%, respectively, vs. 28·7%, were satisfied with their face/chin appearance (SSRS; P < 0·001). Calliper measurements showed a significant reduction in SMF (P < 0·001), skin laxity was not worsened and patients reported improvements in the severity and psychological impact of SMF with ATX-101 vs. placebo. Most adverse events were transient and associated with the treatment area. CONCLUSIONS: ATX-101 was effective and well tolerated for nonsurgical SMF reduction.

[Adverse reaction to fillers. Diagnosis and management]. / Komplikationen auf injizierbare Füllmaterialien. Diagnose und Therapie.

Injectable fillers are an established component of aesthetic medicine. In general they are safe to use. However, adverse reactions are possible for the whole spectrum of products. These reactions can occur immediately, subacute or delayed, e.g. after years. Erythema, edema, abscesses, nodule formation or even ulcerations can be observed. A correct diagnoses of these reactions is important to allow an appropriate treatment, taking into consideration the clinic, the injected material and if applicable other diseases/treatments that might contribute to these reactions. All of these reactions should be reported either to specialized registries and/or to the appropriate national agencies. Only then will we be able to learn more about these reactions and the best possible treatment.

[Injectable fillers: adverse reactions and their management]. / Injizierbare Füllmaterialien: Nebenwirkungen und Management.

Injectable fillers are one of the corner stones of aesthetic medicine. In general they are safe to use. However, adverse reactions may occur. These reactions may be acute, subacute or delayed, e.g. after decades. It is important to know these reactions and to be prepared so that they can be adequately treated, in view of the clinical symptoms, the injected material and if applicable other diseases/treatments that might trigger these reactions. Last but not least, all reactions should be reported either to specialized registries or regulatory agencies. Only then we are able to learn more about these reactions and their best possible treatment.

Efficacy and safety of methantheline bromide (Vagantin(®) ) in axillary and palmar hyperhidrosis: results from a multicenter, randomized, placebo-controlled trial.

BACKGROUND: Focal hyperhidrosis can severely affect quality of life. So far, knowledge on the effect of systemic therapy of focal hyperhidrosis is limited. OBJECTIVE: To assess the efficacy and safety of methantheline bromide (MB) in the treatment of axillary and palmar-axillary hyperhidrosis. METHODS: A multicenter controlled randomized double-blind clinical trial was conducted in patients with axillary or palmar-axillary hyperhidrosis defined by a sweat production >50 mg/5 min. Patients received 3 × 50 mg MB daily or placebo over a period of 28 ± 1 days. Main outcome criterion was the reduction of sweat as measured by gravimetry on day 28 ± 1. Quality of life was assessed by Dermatology Life Quality Index (DLQI) and Hyperhidrosis Disease Severity Score (HDSS). RESULTS: A total of 339 patients were randomly assigned to receive MB or placebo. On day 28 ± 1, the mean axillary sweat production was 99 mg for MB and 130 mg for placebo compared with 168 mg and 161 mg respectively at baseline (P = 0.004). Patient's HDSS score decreased in the MB group from 3.2 to 2.4 compared with 3.2 to 2.7 for placebo (P = 0.002). Similar results could be obtained for the DLQI with 9.7 for MB and 12.2 for placebo, which decreased from 16.4 or 17 respectively (P = 0.003). Tolerability was good for both groups. The most frequent adverse event was dry mouth. CONCLUSION: Fifty milligrams methantheline bromide three times a day is an effective and safe treatment of axillary hyperhidrosis.

[Focal hyperhidrosis.Quality of life, socioeconomic importance and use of internal medicinal therapy]. / Fokale Hyperhidrose. Lebensqualität, sozioökonomische Bedeutung und der Einsatz interner medikamentöser Therapien.

Focal hyperhidrosis can have a substantial influence on the professional, physical, emotional and social life of those affected. This becomes clear when the results of quality of life studies and Health Service Research studies are reviewed, e.g. affected patients were prepared to contribute additional money for treatment of hyperhidrosis. The systemic therapy of focal hyperhidrosis with oral anticholinergic agents is a quite economical treatment strategy. These products can be administered continuously or sporadically. However, only good clinical date for the continous treatment exists. Focal hyperhidrosis is a disease which requires our full attention. It should be discussed whether e.g. QoL questionnaires should be used routinelly.

Efficacy of systemic therapies for moderate-to-severe psoriasis: a systematic review and meta-analysis of long-term treatment.

BACKGROUND: Despite the chronicity of psoriasis, most systematic reviews focus on short-term treatment. METHODS: The systematic search strategy and results from the German Psoriasis Guidelines were adapted. To update the data a literature search in Medline, Embase and the Cochrane Library was conducted. The proportion of participants achieving ≥75% decrease in Psoriasis Area and Severity Index (PASI) as well as Dermatology Life Quality Index (DLQI) reduction at different time points were assessed. Trials were summarized with respect to time periods and study designs. Suitable trials were included in a meta-analysis. Particular attention was paid to statistical approaches of handling dropouts. RESULTS: A total of 33 articles including 27 trials totaling 6575 patients with active treatment were included in the systematic review. Seven randomized controlled trials were eligible for the meta-analysis. Over a 24 week treatment period infliximab [risk difference (RD) 78%, 95% confidence interval (CI) 72-83%] and ustekinumab 90 mg every 12 weeks (RD 77%, 95% CI 71-83%) were the most efficacious treatments. Adalimumab (RD: 60%, 95% CI 45-74%) showed results within the range of different etanercept dosages (etanercept 50 mg once weekly: RD 62%, 95% CI, 52-72%), (etanercept 25 mg twice weekly: RD 45%, 95% CI 34-56%), (etanercept 50 mg twice weekly: RD 56%, 95% CI 49-62%) and (etanercept 50 mg twice weekly until week 12, then 25 mg twice weekly: RD 50%, 95% CI 42-57%). After 24 weeks a decrease in efficacy for inflximab, adalimumab and etanercept was observed. CONCLUSIONS: More sufficient data is required to draw reliable conclusions in extended long-term treatment and head-to-head comparisons are necessary.

German S3-guidelines on the treatment of psoriasis vulgaris (short version).

Psoriasis vulgaris is a common and often chronic inflammatory skin disease. The incidence of psoriasis in Western industrialized countries ranges from 1.5 to 2%. Patients afflicted with severe psoriasis vulgaris may experience a significant reduction in quality of life. Despite the large variety of treatment options available, patient surveys have revealed insufficient satisfaction with the efficacy of available treatments and a high rate of medication non-compliance (Richards et al. in J Am Acad Dermatol 41(4):581-583, 1999). To optimize the treatment of psoriasis in Germany, the Deutsche Dermatologische Gesellschaft (DDG) and the Berufsverband Deutscher Dermatologen (BVDD) have initiated a project to develop evidence-based guidelines for the management of psoriasis first published in 2006 and now updated in 2011. The Guidelines focus on induction therapy in cases of mild, moderate, and severe plaque-type psoriasis in adults. This short version of the guidelines presents the resulting series of therapeutic recommendations, which were based on a systematic literature search and discussed and approved by a team of dermatology experts. In addition to the therapeutic recommendations provided in this short version, the full version of the guidelines includes information on contraindications, adverse events, drug interactions, practicality, and costs, as well as detailed information on how best to apply the treatments described (for full version please see Nast et al. in JDDG Suppl 2:S1-S104, 2011 or http://www.psoriasis-leitlinie.de ).

Adverse reactions caused by consecutive injections of different fillers in the same facial region: risk assessment based on the results from the Injectable Filler Safety study.

BACKGROUND: The combination of different injectable fillers in one area is considered to increase the risk of adverse reactions. OBJECTIVES: To characterize adverse reactions in patients who received more than one filler in the same facial region. METHODS: Data (up to July 2009) of the Injectable Filler Safety Study, a German-based registry for adverse filler reactions, was analysed descriptively. All cases were discussed individually. RESULTS: In 22 of the 161 patients (13.7%), two or more different fillers were injected consecutively into the same facial region. All patients were female with an average age of 50.6 (SD 13.6) years. In 12 of the 22 patients (54.5%), a specific filler could be attributed to the adverse reactions whereas in the other 10 patients (45.5%), the filler was not clearly attributable to one filler substance causing the adverse reactions. CONCLUSIONS: With the continuous changes in the filler market, the combination of different fillers in one area becomes more likely. Based on our data, there is not a lot of evidence that the combination of different injectable fillers, specifically biodegradable fillers, in the same region increases the risk of adverse reactions.

International consensus recommendations on the aesthetic usage of botulinum toxin type A (Speywood Unit)--Part II: Wrinkles on the middle and lower face, neck and chest.

BACKGROUND: Azzalure® (Galderma SA), a newly approved European botulinum neurotoxin type A (BoNT-A), is derived from Dysport™ (Ipsen Ltd.), which has a 20-year history of product consistency and has been widely used for various aesthetic and therapeutic applications. Azzalure® and Dysport™ are collectively referred to as BoNT-A (Speywood Unit) after the unit of their activity, and are distinct from other commercial BoNT-A preparations. Consensus has been developed for the treatment of upper facial wrinkles with BoNT-A (Speywood Unit). OBJECTIVE: To provide consensus recommendations on the treatment with BoNT-A (Speywood Unit) for wrinkles on the middle and lower face, neck and chest region. METHODS: The members of the International Board on Botulinum toxin Azzalure (IBBA) convened to develop consensus based on their extensive experience. RESULTS: The recommended final concentration of BoNT-A (Speywood Unit) is 200 Speywood Units/ml after reconstitution. The consensus recommendations were provided for nine indications, including lower eyelid wrinkles, bunny lines, drooping nasal tip, perioral wrinkles, masseter hypertrophy, drooping mouth corners, dimpled chin, platysmal bands and décolleté wrinkles. For each indication, anatomy of the region to be treated was discussed, as were potential side-effects. The consensus recommendations included the number and location of the injection points, dose range of each point and the total injection, as well as specific injection technique. CONCLUSION: These recommendations provide a guideline for physicians who wish to perform safe and efficacious treatment with BoNT-A (Speywood Unit) on the less commonly treated middle and lower face, neck and chest region.

On the development of the European S3 guidelines on the systemic treatment of psoriasis vulgaris: structure and challenges.

BACKGROUND: The development of evidence based guidelines is a demanding and time consuming process. Therefore it is important to share the knowledge and discuss the structure of these guidelines in detail. OBJECTIVES: To present a method report on the development process of the European evidence based guidelines on the systemic treatment of psoriasis vulgaris with the aim to offer guidance to other guidelines groups with lesser experience and to critically appraise the methodology of the guidelines development process. METHODS: The guidelines are based on the previously evaluated literature from three European national evidence based guidelines and an additional systematic search and evaluation of new literature. Further steps included a structured consensus conference and a DELPHI procedure to develop the recommendations, as well as several internal and external reviews. All steps were coordinated by the Division of evidence based medicine in cooperation with a group of methodologists. RESULTS: A total of 114 studies were included, serving as base for the efficacy chapters of the intervention. The recommendations, based on the efficacy and the level of evidence of the included studies were discussed and finally consented by the guidelines group. After subsequent reviews the guidelines were presented to the European Dermatology Forum, European Academy of Dermatology and Venereology and Union Européenne des Médicins Spécialistes for approval and published in October 2009. CONCLUSION: The development of European evidence based guidelines requires a coordinated structure which can be achieved by the integration of an experienced group of methodologists. Nevertheless further improvements are imaginable and might be considered for an update or other European evidence based guidelines.

International consensus recommendations on the aesthetic usage of botulinum toxin type A (Speywood Unit)--Part I: Upper facial wrinkles.

BACKGROUND: Azzalure (Galderma SA) is a newly approved European botulinum neurotoxin type A (BoNT-A). It is derived from Dysport (Ipsen Pharma), which has a long history of usages in various applications. Azzalure and Dysport are collectively referred to as BoNT-A (Speywood Unit) and are different from other BoNT-A preparations. OBJECTIVE: To provide consensus recommendations on the treatment of upper face wrinkles with BoNT-A (Speywood Unit). METHODS: The members of the International Board on Botulinum toxin Azzalure (IBBA) convened to develop consensus on the treatment of upper facial wrinkles based on their own extensive experience. RESULTS: The consensus recommendations address the general issues regarding treatment and provide specific guidelines on the anatomy, injection points, dose, injection technique and safety precautions concerning each common upper face indication. The recommended final concentration of BoNT-A (Speywood Unit) is 200 s.U/mL (10 s.U/0.05 mL) after reconstitution. For glabellar lines, the members recommend a total of five injection points with 10 s.U/point. For forehead wrinkles, the members recommend four to six injections into the frontalis with 5-10 s.U/point. For crow's feet, the members recommend three injections per side with 5-10 s.U/point at the lateral part of the orbicularis oculi. For lateral eyebrow lift, the members recommend one point at each eyebrow tail and an additional one in each side of the frontalis with 5-10 s.U/point. CONCLUSION: This guideline provides a framework for physicians who wish to perform safe and efficacious injection of BoNT-A (Speywood Unit).

Treatment of glabellar lines with botulinum toxin type A (Speywood Unit): a clinical overview.

Azzalure (Galderma) is a newly approved European botulinum neurotoxin type A (BoNT-A) specifically designed for aesthetic usages. It is sourced from Dysport (Ipsen Ltd.), which has a 20-year product consistency and has been used widely for various therapeutic and aesthetic applications. Azzalure and Dysport are collectively referred to as BoNT-A (Speywood Unit; s.U) (or abobotulinumtoxinA in the U.S.) after their biological activity unit, which is unique and not interchangeable with units of other commercial BoNT-A preparations. Azzalure is approved for the treatment of moderate-to-severe glabellar lines, with a total dose of 50 s.U distributed evenly among 5 injection points. To ensure optimal treatment outcomes with BoNT-A (s.U), it is crucial for injectors to adopt proper methods of reconstitution and injection, which can be acquired through training. We review here the method of reconstitution for BoNT-A (s.U), as well as the injection dose, points and techniques for glabellar line treatment. We also review the efficacy and safety results of BoNT-A (s.U) demonstrated in 11 clinical studies, most of which were randomized, double-blind and placebo-controlled. The studies included assessments after single injections as well as after up to 6 repeated treatment sessions. We summarize the clinical efficacy results, which include the responder rate 1 month post-injection, onset of response and duration of action, as well as safety results, which include incidence of treatment-emergent adverse events and specifically eyelid ptosis. The efficacy and safety profiles reported here are unique to BoNT-A (s.U) and cannot be generalized to other BoNT-A products.