Treatment of keloids using 5-fluorouracil in combination with crystalline triamcinolone acetonide suspension: evaluating therapeutic effects by using non-invasive objective measures.

BACKGROUND: Intralesional 5-fluorouracil (5-FU) in combination with triamcinolone acetonide (TAC) has been recommended as a promising alternative for keloids not responding to silicone-based products, cryotherapy or intralesional corticosteroids alone. Although numerous studies support the efficacy of this regime, there is a lack of objective data. OBJECTIVES: In this study, we evaluate the therapeutic effect of four courses of intralesional 5-FU in combination with TAC (3 : 1) utilizing 3D analysis (PRIMOS®pico ), ultrasound and scar scales such as the Patient and Observer Scar Assessment Scales (POSAS) and the Dermatology Life Quality Index (DLQI). METHODS: Twenty-five patients with keloids were treated using 5-FU and TAC every 4 weeks. Objective assessments were performed and the scar scales administered at baseline, as well as during consecutive visits at 1- and 12-month follow-up (FU). Routine laboratory tests were performed at baseline and at 1-month FU. RESULTS: 3D PRIMOS and ultrasound measurements revealed highly significant and stable reductions in height (baseline mean score: 4.0 ± 1.7 mm, 1-month FU mean score: 1.5 ± 0.8 mm, 12-month FU mean score: 1.8 ± 0.9 mm, P = <0.0001), volume (baseline mean score: 1,105 ± 911.5 mm3 , 1-month FU mean score: 416.1 ± 218.1 mm3 , 12-month FU mean sore: 431.2 ± 253.6 mm3 , P = <0.0001, respectively) and penetration depth of keloids (relative reduction between baseline and 12-month FU of 74.4%, P = <0.0001). The POSAS and DLQI scales confirmed significant objective and subjective improvements in scar appearance in all categories. The life quality associated with keloid appearance improved from a 'moderate effect' to a 'small effect' throughout the course of the study. CONCLUSIONS: Results of this study confirm the efficacy and safety of the combination of 5-FU and TAC in keloids. Treatments were well tolerated and demonstrated stable results at 12-month FU.

Methyl aminolevulinate daylight photodynamic therapy applied at home for non-hyperkeratotic actinic keratosis of the face or scalp: an open, interventional study conducted in Germany.

BACKGROUND: The efficacy and safety of methyl aminolevulinate daylight photodynamic therapy (MAL DL-PDT) for actinic keratosis (AK) treatment has previously been demonstrated in several studies. OBJECTIVE: To evaluate patient-reported outcomes, effectiveness and tolerability of patient self-applied MAL DL-PDT. PATIENTS AND METHODS: An open study was conducted in Germany in patients with thin or non-hyperkeratotic and non-pigmented AK. At baseline, the investigator delimited the target anatomical area and skin preparation was discretionary. On day 1, the patient performed MAL DL-PDT at home, in accordance with instructions (after applying sunscreen and skin preparation by abrasive pad). Patient questionnaires were completed on day 1 and 3 months post-treatment. Effectiveness was assessed by investigator at 3 months. Pain and adverse events (AE) were recorded. RESULTS: Patients (n = 50) were mostly elderly (mean age: 73.4 years) men (86%). After treatment on day 1, 94% of patients were overall satisfied or very satisfied with the treatment and 98% found the instructions convenient. At 3 months, most patients were satisfied or very satisfied with treatment effectiveness (88%) and aspect of their skin (80%). At 3 months, 62% of overall lesions were completely clear. The main related AEs were mild and expected (erythema, procedural pain and skin burning sensation). CONCLUSIONS: Patient self-application of MAL DL-PDT resulted in high levels of patient satisfaction, effectiveness and tolerability.

Evaluation of a non-ablative, fractional 1565 nm laser for the improvement of striae distensae albae.

BACKGROUND AND OBJECTIVE: Striae distensae (SD) represent therapeutically challenging forms of dermal atrophic scarring. In addition to topical ointments, medical needling and various energy-based devices, non-ablative fractional lasers have been suggested for their improvement. However, objective evaluations of their efficacy are widely missing. In this study, we aimed to assess the clinical improvement of SD albae after three treatments with a non-ablative fractional 1565 nm Er: glass laser by employing three-dimensional analysis and several questionnaires. METHODS: A total of 16 Caucasians suffering from SD albae were included in this prospective study. Every patient received three treatments - one every 4 weeks - using a non-ablative, fractional 1565 nm laser (two passes: 300 µbeams/cm2 , 40 mJ inside the SD; 150 µbeams/cm2 , 50 mJ inside the SD and within the surrounding area). Questionnaires (DLQI, POSAS), digital photography and three-dimensional analysis employing PRIMOS® software and VECTRA® camera system were taken at baseline, 1 and 6 months after the last treatment. RESULTS: Evaluation of objective measurements at 6-month follow-up (FU) showed a significant reduction in depth of atrophic lesions by 31.7% and less skin irregularities with Smax at baseline of 621.2 µm decreasing to 411.6 µm (P < 0.01, respectively). Improvement in objective measurements was supported by significant changes in patients' rating of skin appearance. POSAS patient total score declined from 33.5 points to 17.5 points throughout the study (P < 0.001). From baseline to 6-month FU, patients' life quality improved by 68.0% (DLQI score). Procedures showed no lasting negative side-effects and little to no down time. CONCLUSION: The use of a fractional non-ablative 1565 nm laser represents a safe approach for the treatment of SD albae. Clinically observed improvements were supported by significant data from objective measurements. The results achieved at 1-month FU represented at 6-month FU, showing stable clinical improvements.

[Therapy of scars with lasers]. / Laser und Narben.

Scar formation is the consequence of trauma to the skin that affects the deep parts of the dermis. Different scar types like immature, mature, atrophic, hypertrophic, or keloid scars can develop depending on factors like age, anatomic localization, cause of trauma, the course of the healing process, and individual predispositions. Keloids and hypertrophic scars are often associated with itching, pain, tautness of the skin, and functional impairments, thus, leading to significantly reduced quality of life in some patients. However, even seemingly physiologically healed scars can cause tremendous psychological strain as is the case with self-harm scars. Despite increased research efforts, the exact pathomechanisms of excessive scarring are still scarcely understood, and dependably effective treatment options are often lacking. However, through continually improving scientific progress, scar treatment paradigms for a variety of scar types, thus far often dominated by conventional treatment methods, are increasingly complemented by new laser technologies and wavelengths.

Compact plasmonic optical biosensors based on nanostructured gradient index lenses integrated into microfluidic cells.

We report on a compact and cost-effective integrated label-free biosensor configuration which is based on the refractive index sensitivity of the localized surface plasmon resonance (LSPR) of gold nanostructures. Aiming for compactification and miniaturization of the sensor, arrays of nanodiscs were fabricated on the planar surface of a gradient index (GRIN) lens, which acts as a substrate as well as an imaging objective for the light scattered by the gold structures. Integration of the lens into a microfluidic flow cell enabled the controlled exchange of liquid media at the sensor surface. The light scattered by the nanostructures was investigated spatially and spectrally resolved making use of the imaging properties of the GRIN lens. Dynamic spectral analysis during refractive index changes was conducted, revealing high sensitivities of up to 372 nm per refractive index unit for the shift of the LSPR. Biosensing capabilities were demonstrated by the detection of binding of an analyte by means of a testosterone-immunoassay.

[Lidocaine-containing hyaluronic acid filler on a CPM® basis for lip augmentation : Experience from clinical practice]. / Lidocainhaltiger Hyaluronfiller auf CPM®-Basis zur Lippenaugmentation : Erfahrungsberichte aus der Praxis.

BACKGROUND: Lip augmentation with hyaluronic acid fillers is an established procedure. As monophasic polydensified hyaluronic acid products with variable density CPM-HAL1 (Belotero® Balance Lidocaine) and CPM-HAL2 (Belotero® Intense Lidocaine) are qualified for beautification and particularly natural-looking rejuvenation, respectively. OBJECTIVES: Assessment of handling and outcome of lip augmentation using the lidocaine-containing hyaluronic acid fillers CPM-HAL1 and CPM-HAL2. MATERIALS AND METHODS: Data from patients who received lip augmentation by means of bautification and/or rejuvenation using CPM-HAL1 and/or CPM-HAL2 were documented. Observation period was 4 months, with assessment of natural outcome, evenness, handling, fluidity, distribution, malleability, tolerability, as well as patient satisfaction and pain. RESULTS: In total, 146 patients from 21 German centres participated. Physicians rated natural outcome and evenness as good or very good for > 95 % of patients. Handling, fluidity, distribution and malleability were assessed for both fillers as good or very good in > 91 % of patients. At every evaluation point, more than 93 % of patients were very or very much satisfied with the product. A total of 125 patients (85.6 %) experienced transient injection-related side effects. Pain intensity during the procedure was mild (2.72 ± 1.72 on the 0-10 pain assessment scale) and abated markedly within 30 min (0.42 ± 0.57). CONCLUSIONS: Lip augmentation with hyaluronic acid fillers produced a long-term cosmetic result. Due to the lidocaine content, procedural pain was low and transient. Accordingly, a high degree of patient satisfaction was achieved that was maintained throughout the observation period.

Non-invasive diagnosis of sweat gland dysplasia using optical coherence tomography and reflectance confocal microscopy in a family with anhidrotic ectodermal dysplasia (Christ-Siemens-Touraine syndrome).

BACKGROUND: Anhidrotic ectodermal dysplasia (AED) is an inherited syndrome, which originates mainly from genetic alteration of the ectodysplasin A (EDA) gene. It regularly affects the adnexa of the skin which results in a characteristic phenotype of the patients including hypo- or anhidrosis leading to severe disturbances in the regulation of body temperature. OBJECTIVES: To prevent the development of the symptoms in early childhood promising therapeutic approaches are currently under clinical investigation. In this context, timely diagnosis of this genetic syndrome is crucial. The purpose of our study was the investigation of modern non-invasive imaging methods such as optical coherence tomography (OCT) and reflectance confocal microscopy (RCM) in the immediate diagnosis of AED. METHODS: We examined a 3-year-old boy with the suspicion for an AED syndrome and his family members with RCM and OCT to document presence and characteristic features of sweat glands in comparison to non-affected individuals. RESULTS: The patient and the affected brother showed significantly reduced sweat glands in the imaging compared to the controls. The genetic analysis revealed a mutation of the EDA gene for hemizygosity previously associated with AED and the mother was revealed as the conductor of the genetic alteration. CONCLUSIONS: With the help of non-invasive imaging, we were able to detect sweat gland dysplasia in the affected family members without performing a biopsy which led us to the diagnosis of an AED. The application of modern dermatological imaging techniques might serve as valuable supplementary tools in the immediate, non-invasive diagnosis of genetic syndromes especially in newborns when early therapeutic approaches are planned.

[Therapeutic approaches for the treatment of facial aging]. / Therapiekonzepte zur Behandlung des "alternden Gesichts".

Over the last few decades, a magnitude of novel therapeutic approaches to battle the signs of facial aging have become available in esthetic dermatology. Comprehensive research in this area has significantly improved our understanding of the anatomy and physiology of facial aging. In order to successfully address age-related alterations in the human face, today's anti-aging treatment frequently necessitates multifaceted options. Alongside botulinum toxin and fillers, a plethora of different modalities are currently available to complete our esthetic portfolio, which are discussed in this review.

[Management and prevention of adverse events in esthetic interventions]. / Nebenwirkungen von ästhetischen Behandlungen und deren Vorbeugung.

BACKGROUND: Esthetic interventions are an integral part of today's dermatology. A plethora of novel agents and techniques is currently being launched on the market accompanied by a variety of side effects. METHOD: We summarize the most common adverse events of fillers, laser treatments, and injection of botulinum toxin and present feasible means of prevention and management. RESULTS: The profile of adverse events is more favorable in temporary fillers such as hyaluronic acid than in permanent ones. The most common filler-related adverse events include changes of skin color and unspecific swelling. Neural and vascular dysfunctions are observed less frequently, but may result in severe tissue necrosis or loss of vision. Undesirable events of laser treatments largely depend on the applied modality, localization, and indication. Local effects comprise erythema, swelling, crusting, blister formation, and weeping in extreme cases. The formation of laser-induced scarring is more likely to occur in lasers with high energies. Most adverse events of botulinum toxin are mild and transient. Pain and redness around the sites of injection are common. However, a poor injection technique and injection of too many units can trigger major motoric impairment with ptosis and dysarthria. CONCLUSION: Excellent results can be achieved with esthetic interventions. To guarantee a maximum amount of safety and to minimize risks it is of paramount importance to work with clear indications and respect contraindications. It is important to recognize early adverse events to achieve satisfactory results and avoid severe complications.

[Fillers and associated side effects]. / Filler und ihre Nebenwirkungen.

BACKGROUND: A variety of fillers is commonly used for tissue augmentation as well as skin rejuvenation, and consist of a large heterogeneous group of biomaterials. The objective was to provide an overview and classification of the most commonly injected filler materials and filler-related complications including therapy. METHOD: A summary of the current literature and common associated side effects is provided from a personal clinical perspective. RESULTS: According to degradability, filler materials can be classified as temporary (degradable), semi-permanent, and permanent (nondegradable). Temporary fillers such as hyaluronic acid and collagen are completely degraded by the surrounding tissue within several months. Semi-permanent fillers are degradable, but may induce longer-lasting secondary effects. Permanent fillers such as silicone and mineral oil derivatives are not biodegradable and have been increasingly abandoned because of severe and irreversible side effects. The most common filler-related adverse events include pigmentation changes, edema and post-injection deformations. Visible or palpable nodules can be due to filler accumulation, formation of granuloma, or infection. CONCLUSIONS: Substantial knowledge of the chemical and clinical features of the injected materials is indispensable for safe and efficient application. Early recognition of filler-related adverse effects is important to avoid severe complications and to achieve optimal results.

The dermatology life quality index as a means to assess life quality in patients with different scar types.

BACKGROUND: Measuring quality of life through questionnaires is a common method to evaluate the impact of different afflictions on the patient's well-being, especially in the field of dermatology where appearance changing afflictions are common. OBJECTIVES: A variety of questionnaires has been used to distinguish different skin conditions like psoriasis, atopic dermatitis and scars. Using the Dermatology Life Quality Index (DLQI), we investigated different scar types regarding their impact on quality of life. METHODS: We assessed the quality of life in 130 patients presenting to our outpatient scar clinic for the first time using the DLQI. Scars were analysed according to their clinical appearance (physiological scars, keloids, hypertrophic scars, atrophic scars, self-harm scars). Physiological scars were established as a baseline for further comparison between groups. RESULTS: Patients in the physiological scar group scored a mean DLQI score of 2.07 ± 3.56, patients in the keloid-, hypertrophic scar-, atrophic scar- and self-harm scar group scored values of 6.06 ± 4.00, 2.53 ± 2.48, 7.26 ± 6.72 and 12.00 ± 3.85 respectively. When compared to the baseline group the difference in the overall score for keloids was +3.99 (P < 0.001), hypertrophic scars scored +0.45 (ns), atrophic scars +5.19 (P < 0.01) and self-harm scars +9.93 (P < 0.001). CONCLUSION: Using the DLQI, we could demonstrate that different subsets of pathological scars do affect patients in a different magnitude. The DLQI provides a promising adjunct for quantifying the quality of life in patients suffering from keloids, atrophic- and self-harm scars and may constitute an interesting additional tool for monitoring the progress of scar treatments.

[Massive granuloma formation after long-term use of dermal fillers]. / Ausgeprägte Granulombildung nach langjähriger dermaler Fillerinjektion.

BACKGROUND: Since dermal fillers were introduced in 1981, millions of patients have undergone wrinkle treatment with dermal fillers. Except for autologous fat, all fillers can act as potential foreign bodies, which have the potential ability to induce an immune reaction. Persisting material may induce activation of the immune system and finally granuloma formation. Frequency, histology, and clinical presentation of such foreign body reactions may vary depending on the filler used. CASE REPORT: This case describes a patient who received innumerable filler injections over the last two decades presenting with massive facial granulomas.

Pentacyclic triterpenes from Terminalia arjuna show multiple benefits on aged and dry skin.

BACKGROUND: Pentacyclic triterpenoids improve epidermal barrier function and induce collagen production. Here, their effects on cutaneous aging by means of objective instrumental measurements were elucidated. METHODS: Reconstituted human epidermis, cultivated keratinocytes and fibroblasts were incubated with Terminalia arjuna triterpenes (T. arjuna bark extract), and mRNA and protein expression of various genes was determined using microarray analysis, qRT-PCR and ELISA techniques. Clinical efficacy of T. arjuna bark extract versus vehicle control cream was elucidated in 30 patients and transepidermal water loss (TEWL), skin hydration and elasticity were measured. Another 30 female patients in their postmenopausal phase were treated with a similar regime, and skin sebum content, cutaneous blood microcirculation and skin density/echogenicity were assessed. RESULTS: Incubation with T. arjuna triterpenes increased FGF-2, TSP-1, TGF-ß and CTGF expression, and VEGF secretion in vitro. Elevated lactate dehydrogenase release upon sodium dodecyl sulphate challenge was reversed by the application of T. arjuna bark extract. T. arjuna bark extract decreased TEWL, improved skin moisturization, reduced scaliness and led to significantly improved skin elasticity. Also, increases in blood microflow and skin sebum content as well as improved skin thickness/echogenicity were noted on postmenopausal skin, resulting in visible reduction of sagging skin on the jowls as demonstrated by digital photography. CONCLUSION: T. arjuna bark extract appears as an innovative active ingredient that exerts versatile antiaging properties in vitro and in vivo.

Erythema a computatro.

Historically, erythema ab igne (EAI) was commonly seen on the shins of individuals working in front of coal stoves or sitting close to a fireplace. In the more recent past, this condition has been primarily observed after repeated application of heating pads. Today, unintentional and unperceived exposure to heat from laptop computers needs to be considered as a potential trigger. A rising number of laptop-induced cases of EAI have been reported recently. For this modern-age version of classic EAI, we propose thus the more accurate neo-Latin term erythema a computatro.

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.

[Unusual faces of syphilis]. / Die ungewöhnlichen Gesichter der Syphilis.

The challenging "great masquerader" is resurgent! For several years syphilis has shown an increasing incidence across Europe and its variable manifestations necessitate its inclusion amongst many differential diagnoses. Using serological tests, it is possible to accurately diagnose syphilis, initiate stage-appropriate therapy and exclude co-infections. In this article, we feature nine unusual presentations of secondary syphilis. In four cases, serology confirmed HIV co-infection.

Development of a modified grating coupler in application to geosciences.

A grating coupler system has been developed to measure refractive index gradients with high spatial (6.7 µm) and temporal (milliseconds) resolution. The system was applied to two-phase model systems consisting of water and non-aqueous pollution liquids. Refractive index gradients at the interfaces between the aqueous and organic phase of 1-butanol, hexane, and 1-heptanol were monitored under steady-state conditions. The temporal resolution was utilized in diffusion experiments with glycerol and sodium chloride in water, where the formation of a concentration gradient was studied. In a further application, the grating coupler system was modified to monitor low-level concentrations of aqueous pollution profiles as are caused by bacterial degradation in the aqueous phase. Toluene was selected as contaminant. The sensor sensitivity was improved by coating the sensor with the pre-concentrating polymers polydimethylsiloxane and Teflon(®) AF-2400. With the grating coupler setup, a multi-purpose instrument was created to measure high-resolution refractive index gradients with high temporal and spatial resolution in different fields of application. The new sensor system can be used to measure absolute refractive indices by covering parts of the sensing area with cover media of known refractive index. Coatings can be used for sensitivity improvement by pre-concentrating the sample, for selectivity by utilizing filtering properties of the coating, and as calibration standard for absolute refractive index measurements.