Longitudinal assessment of autonomic nervous system in patients with first demyelinating event suggestive of multiple sclerosis.

BACKGROUND AND PURPOSE: As a high proportion of people with clinically isolated syndrome (pwCIS) exhibit sympathetic adrenergic and sudomotor dysfunction, the aim of this study was to investigate the evolution of autonomic nervous system (ANS) abnormalities in pwCIS over a 2-year follow-up. METHODS: This was a prospective cohort study in which 121 pwCIS were enrolled and followed for 2 years. After 2-year follow-up, data were available for 84 pwCIS. ANS symptoms were evaluated with the Composite Autonomic System Score-31 (COMPASS-31) and results of the ANS tests were expressed using the Composite Autonomic Scoring Scale (CASS) at baseline and visit at month 24. Symptomatic dysautonomia was defined if the patient had a COMPASS-31 value above the median of the whole cohort at baseline evaluation (COMPASS-31 > 6.79) and CASS score >0. RESULTS: Complete CASS data at baseline and month 24 were available for 62 patients; in 24 (38.7%) patients there was worsening, in 16 (25.8%) there was improvement and in 22 (35.5%) there was no change in CASS score. In 90% of pwCIS (72 of 80) there was no change in parasympathetic nervous system tests, whereas 47.3% (35 of 74) had either worsening or improvement in sympathetic adrenergic and 28.6% (20 of 70) had either worsening or improvement in sudomotor function. A multivariable regression model identified the total number of T2 lesions as an independent predictor for worsening of symptomatic dysautonomia. No predictors for worsening or improving of CASS score were identified. CONCLUSION: A substantial proportion of pwCIS experienced worsening of ANS abnormalities during the 2-year follow-up and magnetic resonance imaging parameters seemed to predict these abnormalities.

High-definition optical coherence tomography and reflectance confocal microscopy in the in vivo visualization of a reaction to permanent make-up.

BACKGROUND AND OBJECTIVES: After permanent make-up treatments, eczematous and granulomatous reactions may occur which need anti-inflammatory treatment. For the definite diagnosis oftentimes biopsies are recommended. In vivo imaging such as reflectance confocal microscopy (RCM) and high-definition optical coherence tomography (HD-OCT) has been successfully used in the non-invasive diagnosis of various dermatoses before. METHODS: Here, we report on non-invasive imaging of a reaction towards permanent make-up in a 40-year-old woman by using HD-OCT and RCM. RESULTS: Both in HD-OCT and in RCM subepidermal pigment and granulomatous changes could be visualized and correlated with the histopathological findings. Regression of the lesions in response to topical steroids and intralesional injections of steroids and 5-fluorouracil is reported and treatment options are discussed. CONCLUSION: Non-invasive imaging techniques such as HD-OCT and RCM allow the visualization and localization of exogenous pigment and help in the evaluation of adverse reactions due to permanent make-up tattooing.

Botulinum toxin A for the treatment of keloids.

INTRODUCTION: Keloids are the result of excessive scar tissue formation. Besides their poor aesthetic appearance, keloids can be associated with severe clinical symptoms such as pain, itching, and rigidity. Unfortunately, most therapeutic approaches remain clinically unsatisfactory. Recently, injections with botulinum toxin A (BTA) were proposed for the treatment of established keloids in a clinical trial. In this study, we aimed to verify the effects of intralesional BTA for the treatment of therapy-resistant keloids using objective measurements. In addition, the underlying molecular mechanisms were investigated using cultured keloid-derived fibroblasts. MATERIALS AND METHODS: Four patients received BTA (doses varying from 70 to 140 Speywood units per session) injected directly into their keloids every 2 months for up to 6 months. Differences in height and volume were evaluated clinically and measured with a 3-D optical profiling system. Keloid-derived fibroblasts were treated with different concentrations of BTA, and expression of collagen (COL)1A1, COL1A2, COL3A1, TGF-ß1, TGF-ß2, TGF-ß3, fibronectin-1, laminin-ß2, and α-SMA was determined by real-time quantitative PCR. MTT and BrdU assays were used to analyze the effects of BTA on fibroblast proliferation and metabolism. RESULTS: Intralesional administration of BTA did not result in regression of keloid tissue. No differences in expression of ECM markers, collagen synthesis, or TGF-ß could be observed after BTA treatment of keloid fibroblasts. In addition, cell proliferation and metabolism of keloid fibroblasts was not affected by BTA treatment. CONCLUSION: The suggested clinical efficiency of intralesional BTA for the therapy of existent keloids could not be confirmed in this study. Based on our data, the potential mechanisms of action of BTA on keloid-derived fibroblasts remain unclear.

Fifty-kDa hyaluronic acid upregulates some epidermal genes without changing TNF-α expression in reconstituted epidermis.

BACKGROUND: Due to its strong water binding potential, hyaluronic acid (HA) is a well-known active ingredient for cosmetic applications. However, based on its varying molecular size, skin penetration of HA may be limited. Recent studies have demonstrated that low-molecular-weight HA (LMW HA) may show a certain proinflammatory activity. We thus aimed to characterize an LMW-sized HA molecule that combines strong anti-aging abilities with efficient skin penetration but lacks potential proinflammatory effects. METHODS: Total RNA and total protein were isolated from reconstituted human epidermis following incubation with HAs of various molecular weights (20, 50, 130, 300, 800 and 1,500 kDa). Tumor necrosis factor-α expression was determined using quantitative PCR. Genomic and proteomic expression of various junctional proteins was determined using Affymetrix and common Western blotting techniques. RESULTS: LMWHA of approximately 50 kDa did not significantly alter tumor necrosis factor-α expression compared to 20-kDa HA, but revealed significantly higher skin penetration rates than larger sized HA associated with increased expression of genes and proteins known to be involved in tight junction formation and keratinocyte cohesion. CONCLUSION: LMW HA of approximately 50 kDa shows better penetration abilities than larger-sized HA. In addition, LMW HA influences the expression of various genes including those contributing to keratinocyte differentiation and formation of intercellular tight junction complexes without showing proinflammatory activity. These observations contribute to current knowledge on the effects of LMW HA on keratinocyte biology and cutaneous physiology.

[Fillers. An overview]. / Dermatofiller. Ein aktueller Uberblick.

The demand for minimally invasive cosmetic procedures is increasing rapidly every year. In addition to botulinum toxin and laser treatments, the injection of dermal fillers is one of the most relevant methods. Dermal fillers can be used for a multitude of indications: wrinkles (fine to deep), lip augmentation, facial deformities, sunken scars, and HIV-related lipoatrophy in hands, neck and décolleté. There are currently 160 dermal fillers on the market. They differ greatly in terms of origin (own or cadaveric-derived, animal, bacterial fermentation or synthesis), duration of the effect and breakdown properties (temporary, semi-permanent, permanent), injection depth (dermal, subcutaneous, supraperiosteal), and risk profile. Physicians who administer dermal fillers should have a thorough knowledge of their characteristics and of the anatomy of the area to be treated. This is essential for correct administration and optimal aesthetic results. Prior to any treatment, details of the procedure, the desired effects, durability, and potential risks of the filler to be injected should be discussed with the patient. The choice of dermal filler, the injection technique, and the volume to be administered are determined according to the anatomic site, the type of defect, the desired effect, and physician experience.

Pimecrolimus cream (1%) efficacy in perioral dermatitis - results of a randomized, double-blind, vehicle-controlled study in 40 patients.

BACKGROUND: Perioral dermatitis (POD) is a common skin disease and difficult to treat. Pimecrolimus cream (1%) successfully controls atopic eczema. OBJECTIVE: Our aim was to investigate its efficacy in POD. STUDY DESIGN: Single-centre, randomized, double-blind, vehicle-controlled study including 40 POD patients with a 4-week treatment and a 4-week follow-up. Efficacy was assessed by a novel Perioral Dermatitis Severity Index (PODSI) and Finlay's Dermatology Life Quality Index (DLQI). SETTING: Outpatient clinics of a large dermatological hospital in Munich, Germany. RESULTS: During treatment, the PODSI was significantly lower in the pimecrolimus group compared with vehicle (P = 0.005-0.02) whereas at follow-up, no significant differences were observed. At week 2, the responder rates (> or = 50% PODSI improvement) were 50% with pimecrolimus cream (1%) and 25% with vehicle (P = 0.095). DLQI was improved in pimecrolimus group compared with vehicle. CONCLUSION: Results suggest that pimecrolimus cream (1%) effectively treats acute-stage POD.

Anti-microbial and -inflammatory activity and efficacy of phytosphingosine: an in vitro and in vivo study addressing acne vulgaris.

Lipids are important constituents of the human epidermis. Either free and organized into broad lipid bilayers in the intercorneocytes spaces, or covalently bound to the corneocyte envelope, they play a crucial role in permeability barrier function and are major contributors to cutaneous anti-microbial defense. Free sphingoid bases are a recent addition to this family of active lipids, which emerged from studies of breakdown products from ceramides. Phytosphingosine (PS) is a lipid occurring naturally in the stratum corneum, both in its free form and as a part of the major fraction of ceramides. The biotechnological production of PS patented by Degussa yields to PS with the correct configuration present in the skin. So, application of a PS containing formulation leads to its integration into the natural lipid structures of the skin. In acne, different pathogenetic factors contribute to the inflammation process, defect in keratinization, increased sebaceous gland activity and increased colonization of Propionibacterium acnes. The results of in vitro and in vivo studies confirm the previous reports on strong anti-microbial effectiveness of skin-identical PS produced by Degussa in vitro and in vivo. In addition, PS shows excellent clinical results in the context of skin care in acne, based on both anti-inflammatory and anti-microbial activity. These results demonstrate the potential of PS to enhance or complement existing acne therapies acting as an active cosmetic ingredient.

[Diagnosis and treatment of eyelid eczema. An interdisciplinary challenge]. / Diagnostik und Therapie des Lidekzems. Eine interdisziplinäre Herausforderung.

Eyelid eczemas are clinically and therapeutically clearly delineated, but remain a pathogenetically heterogeneous entity. The anatomic and functional conditions in the periorbital region make treatment difficult. Thus, in addition to frequent resistance to therapy and a tendency to recur, they pose a considerable diagnostic and therapeutic challenge to dermatologists and ophthalmologists. Even a comparatively small area of eyelid eczema can cause substantial suffering because of the burdensome symptoms and high aesthetic significance of this body region. This interdisciplinary overview deals in particular with current pathogenetic and therapeutic aspects of eyelid eczemas.