State of the art: systemic rosacea management.

Based on numerous trials, oral tetracyclines and most commonly their second-generation derivative doxycycline have become the main pillar in systemic rosacea treatment. However, the only preparation that has been approved so far in this setting is 40 mg doxycycline in an anti-inflammatory dosage and with a modified release formulation. With the introduction of this once-daily, non-antibiotic dosing of doxycycline, oral therapy is more commonly prescribed as first-line treatment in moderate to severe papulopustular rosacea. In addition, topical and oral strategies are often used in combination due to the more substantial improvements compared to monotherapy. Although several other non-approved oral agents like macrolides, isotretinoin, and carvedilol have been evaluated for systemic treatment and showed promising results, yet the experience with these drugs in rosacea is limited, and thus they should be reserved for special situations.

Aktueller Stand der systemischen Rosazea-Therapie.

Basierend auf den Daten zahlreicher Studien sind orale Tetracycline - und hier insbesondere Doxycyclin als Tetracyclin der zweiten Generation - die Grundpfeiler der systemischen Rosazea-Therapie. Bisher ist dafür jedoch nur Doxycyclin 40 mg in antientzündlicher Dosierung mit veränderter Wirkstofffreisetzung zugelassen. Seit Einführung der Therapie mit Doxycyclin einmal täglich in nicht antibiotischer Dosierung wird die orale Therapie häufiger als Erstbehandlung bei mittelschwerer bis schwerer papulopustulöser Rosazea verschrieben. Oft wird diese Behandlung aufgrund der besseren Wirksamkeit im Vergleich zur Monotherapie auch mit einer topischen Behandlung kombiniert. Obwohl in der Systemtherapie weitere, nicht zugelassene Wirkstoffe wie Makrolide, Isotretinoin und Carvedilol mit viel versprechenden Ergebnissen untersucht wurden, ist die vorliegende Erfahrung bisher begrenzt, so dass diese Substanzen speziellen Situationen vorbehalten bleiben sollten.

Rosazea-Management: Update über allgemeine Maßnahmen und topische Therapieoptionen.

Obwohl bislang für die Rosazea keine kurative Therapie besteht, können verschiedene Optionen zur Behandlung der Symptome und zur Vorbeugung von Exazerbationen empfohlen werden. Neben Selbsthilfemaßnahme wie der Vermeidung von Triggerfaktoren und einer geeigneten Hautpflege sollte das Rosazea-Management bei Patienten mit erythematöser und leichter bis schwerer papulopustulöser Rosazea die Anwendung topischer Präparate als First-Line-Therapie umfassen. Da Überlappungen der charakteristischen Rosazea-Symptome im klinischen Alltag die Regel sind, sollte die medikamentöse Therapie auf die individuellen Symptome zugeschnitten werden; auch eine Kombinationstherapie kann erforderlich sein. Zu den für die Behandlung der Hauptsymptome der Rosazea zugelassenen Wirkstoffen gehören Brimonidin gegen das Erythem sowie Ivermectin, Metronidazol oder Azelainsäure gegen entzündliche Läsionen. Ihre Wirksamkeit wurde in zahlreichen validen, gut kontrollierten Studien belegt. Darüber hinaus existieren verschiedene nicht zugelassene topische Behandlungsmöglichkeiten, deren Wirksamkeit und Sicherheit noch in größeren, kontrollierten Studien zu untersuchen ist.

Rosacea Management: Update on general measures and topical treatment options.

Although there is presently no cure for rosacea, there are several recommended treatment options available to control many of the symptoms and to prevent them from getting worse. In addition to self-help measures like avoidance of trigger factors and proper skin care, rosacea management should include topical medications as one of the first-line choices for patients with erythematous and mild to severe papulopustular rosacea. Since mixed forms of characteristic rosacea symptoms are more common, medical treatment must be symptom-tailored for each individual case and will often involve a combination therapy. Approved topical agents for the major symptoms of rosacea encompass brimonidine for erythema and ivermectin, metronidazole or azelaic acid for inflammatory lesions, all of which have shown their efficacy in numerous valid, well-controlled trials. In addition, there are several other, not approved topical treatments which are possible options that require further validation in larger well-controlled studies.

Superiority of ivermectin 1% cream over metronidazole 0·75% cream in treating inflammatory lesions of rosacea: a randomized, investigator-blinded trial.

BACKGROUND: Few therapeutic alternatives currently exist in the treatment of papulopustular rosacea (PPR). OBJECTIVES: To demonstrate superiority of once-daily ivermectin 1% cream (IVM 1%) once daily vs. twice-daily metronidazole (MTZ 0·75%) cream, regarding percentage reduction of inflammatory lesions in subjects with moderate to severe PPR. METHODS: In this Phase 3, investigator-blinded, randomized, parallel-group study, subjects received IVM 1% once daily, or MTZ 0·75% twice daily over 16 weeks. Efficacy assessments were inflammatory lesion counts and Investigator's Global Assessment (IGA). Safety assessments included incidence of adverse events (AEs) and local tolerance parameters. Subjects evaluated their disease following a 5-grade scale and completed questionnaires. RESULTS: A total of 962 subjects were randomized to receive IVM 1% (n = 478) or MTZ 0·75% (n = 484). At week 16, IVM 1% was significantly superior to MTZ 0·75% in terms of reduction from baseline in inflammatory lesions (83·0% vs. 73·7%; P < 0.001), observed as early as week 3 (Last Observation Carried Forward, LOCF). IGA results (subjects 'clear' or 'almost clear') also favoured IVM 1%: 84·9% vs. 75·4%, respectively (P < 0.001). Incidence of AEs was comparable between groups and local tolerability was better for IVM 1%. More subjects receiving IVM rated their global improvement as 'excellent' or 'good.' CONCLUSIONS: Ivermectin 1% cream was significantly superior to MTZ 0·75% cream and achieved high patient satisfaction.

[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.

Treatment of Darier disease with oral alitretinoin.

Darier disease (DD) is an autosomal dominant skin disease. Treatment is often difficult and unsatisfactory because of the chronic nature of the condition and the irritant potential of various therapeutic agents. Systemic vitamin A derivatives such as acitretin and isotretinoin are the treatment of choice, but their use is often limited by class-specific side-effects. Alitretinoin (9-cis-retinoic acid), has antiproliferative and anti-inflammatory potential, and is licensed for the systemic treatment of chronic hand eczema in a number of countries. Unlike acitretin, alitrenoin requires contraception in women of childbearing age to be extended for only 1 month after the end of treatment. There is evidence that alitretinoin might be a well-tolerated alternative for the systemic treatment of various retinoid-responsive skin diseases. We present two cases of women with refractory DD successfully treated with alitretinoin without marked side-effects, who both obtained near-complete remission of their skin lesions.

Knowledge of sexually transmitted HPV infection, genitoanal warts, cancer and their prevention among young females after vaccine introduction in Germany.

BACKGROUND: Sexually transmitted human papillomavirus (HPV) high-risk types cause carcinoma and low-risk types lead to warts of genitoanal area. Since the HPV vaccine has been introduced, awareness of HPV infection, prevention and health-related behaviour have not been studied in a large sample of young women in Germany. OBJECTIVES: Assessment of awareness and health-related behaviour regarding HPV infection and prevention among young German females. METHODS: In 2010, a postal cross-sectional survey was conducted with a random representative sample size (n = 2000) of females aged 19-35 attending Germany's largest (comprehensive) university, which was designed to obtain data about socio-demographics, the awareness of sexually transmitted HPV, genitoanal neoplasms and their prevention, HPV vaccine, immunisation and cervical cancer screening. RESULTS: Of the 547 (27.3%) participants, 69.1% had heard of HPV, 62.5% were aware of the vaccine, 14.4% were vaccinated and 6.9% reported a history of sexually transmitted infection, including HPV (2.7%). The HPV-related knowledge among those who had heard of it was high (75.1-99.7%), except of that HPV affects men (52.9%) and HPV's causative role in genital (54.2%) and anal (35.6%) warts, and smoking (11.3%) as an HPV risk factor. The lower HPV knowledge score (

[Recurrent fibrosarcomatous dermatofibrosarcoma protuberans. Ultrasound imaging]. / Rezidiv eines fibrosarkomatösen Dermatofibrosarcoma protuberans. Sonographische Darstellung.

Dermatofibrosarcoma protuberans (DFSP) is a rare dermal tumor of intermediate malignancy with a locally aggressive growth behavior with a high rate of recurrence. Wide local excision with histographic margin control as well as regular follow-ups including clinical as well as ultrasound examination are crucial to detect local recurrence or metastasis. Ultrasound imaging can not only identify recurrences but also asses their extent. We report on a patient with a relapse of fibrosarcomatous DFSP, which could be demonstrated by ultrasound imaging.

SCORAD 75: a new metric for assessing treatment outcomes in atopic dermatitis.

OBJECTIVE: The scoring atopic dermatitis (SCORAD) is a well-established severity-scoring tool for atopic dermatitis (AD). Dead Sea climatotherapy (DSC) is a natural selective balneo-phototherapy utilized for many years to treat severe AD. The study's goal was to evaluate the impact of DSC on AD patients through assessment of SCORAD scores and to identify parameters associated with greater improvement. METHODS: The files of 78 European patients (37 male patients and 41 female patients, mean age 37.8 years) with AD undergoing DSC were included in this retrospective study. Three sub-groups were delineated based on disease severity (as determined using the SCORAD). Demographic and clinical parameters as well as treatment characteristics--maximal and cumulative sun exposure doses--were recorded. SCORAD values were again recorded for assessment of treatment response. SCORAD 75 was defined as ≥75% decrease in SCORAD values following therapy. Statistical analysis including logistic regression models was used in multivariable analysis. RESULTS: After an average of 30 days of treatment, mean SCORAD values dropped from 50.5 to 11 (76.7%, P<0.001). 64.1% of all patients, regardless of sub-group, reached SCORAD 75, whereas 78.9% of patients with severe disease achieved this result. In a multivariate logistic regression, factors associated with achieving SCORAD 75 were maximal sun exposure, family history of AD and age at disease onset (P=0.002, P=0.009 and P=0.040 respectively). CONCLUSION: Dead Sea climatotherapy is a particularly effective treatment method for the sub-population of adults with severe AD. The SCORAD 75 can be useful for defining sub-populations in which treatment is more likely to be successful.

[Surgical management of Pyoderma gangrenosum]. / Chirurgische Therapie beim Pyoderma gangraenosum.

Pyoderma gangrenosum is a rare affection of unknown etiology, which is often associated with systemic diseases such as chronic inflammatory bowel disease, hematologic disorders, carcinomas and arthritis. Treatment may include topical corticosteroids or calcineurin inhibitors in combination with systemic corticosteroids, cyclosporine A, azathioprine, cyclophosphamide, mycophenolate mofetil, intravenous immunoglobulins or monoclonal antibodies against TNFα but all these approaches are off-label. Surgical therapy is difficult because of pathergy. Nevertheless, after having stopped the inflammation, the ulcers can be treated by split thickness skin grafts and simultaneous immunosuppression. We present three cases with successful surgical treatment.

[Ulcers following therapy with hydroxyurea. Three case reports and review of the literature]. / Ulzerationen unter Therapie mit Hydroxyharnstoff. Drei Fallberichte mit Literaturüberblick.

Hydroxyurea is frequently used for therapy of myeloproliferative disorders. One cutaneous side-effect is painful, therapy-resistant ulcers which have bizarre configurations and occur at atypical sites for venous ulcers. Improvement or healing often first occurs when hydroxyurea is discontinued. We report on one patient with essential thrombocythemia and two with polycythemia vera, who developed such ulcers during hydroxyurea therapy. In one case, the ulcers developed shortly after hydroxyurea was started. In addition we give a short overview of the current literature.

Topical treatment of perianal eczema with tacrolimus 0.1%.

BACKGROUND: Perianal eczema is an inflammatory skin disease with a high prevalence in most industrialized countries. As general practitioners and dermatologists frequently see patients with perianal eczema the need for efficient, fast and safe therapies is high. Topical calcineurin inhibitors such as tacrolimus (FK506) ameliorate cutaneous inflammation and associated pruritus in an array of inflammatory dermatoses. OBJECTIVES: To investigate the effect of topical tacrolimus in perianal eczema. METHODS: Twenty-four patients with perianal eczema were treated with tacrolimus 0.1% ointment twice daily on the affected skin area for 2 weeks. RESULTS: All returning patients showed clinical improvement as assessed by macroscopic appearance and clinical score (modified SCORAD index). CONCLUSIONS: In this short-term trial we demonstrate that topical tacrolimus 0.1% is safe, efficient and well tolerated in patients with perianal eczema irrespective of the underlying cause.

Targeted treatment of pyoderma gangrenosum in PAPA (pyogenic arthritis, pyoderma gangrenosum and acne) syndrome with the recombinant human interleukin-1 receptor antagonist anakinra.

The triad of sterile pyogenic arthritis, pyoderma gangrenosum and acne is known by the acronym of PAPA syndrome. It is a rare autosomal dominant disease of early onset. The treatment of pyoderma gangrenosum is challenging as there is often only partial response to systemic glucocorticosteroids and immunosuppressive therapies. We report the rapid and lasting response of pyoderma gangrenosum to the targeted treatment with the recombinant human interleukin-1 receptor antagonist (rHuIL-1Ra) anakinra in a patient with PAPA syndrome.

An innovative water-soluble biopolymer improves efficacy of ciclopirox nail lacquer in the management of onychomycosis.

BACKGROUND: A new 8% ciclopirox-medicated nail lacquer (P-3051), based on a new technology, revealed superior properties in terms of affinity to keratin, nail permeation, and ease of use. OBJECTIVE: This study aims to assess the efficacy and safety of P-3051 vs. the market 8% ciclopirox nail lacquer. METHODS: This is a multicentre, randomized, three-arm, placebo-controlled, parallel groups, evaluator-blinded study. Overall, 467 patients with onychomycosis of at least one big toenail were randomized to receive P-3051, the reference drug or placebo in a 2 : 2 : 1 ratio for a 48-week treatment by daily application, followed by a 12-week follow-up. RESULTS: The study satisfied its objective by demonstrating that P-3051 was both superior to placebo and non-inferior to reference in the complete cure rate after a 48-week active treatment period. Switching the non-inferiority to superiority hypothesis, the superiority of P-3051 vs. reference was nearly significant at week 48 (confirmed at week 52), and it was significant at week 60 (cure rate for P-3051 is 119% higher than reference; P < 0.05). Altogether, the results on primary endpoint exceed expectations; superiority test was performed also on secondary endpoints to confirm the superiority trend of the study. At the end of follow-up, percentages of patients who achieved the endpoint 'responder' in the P-3051 group were 66% higher than reference (P < 0.05), and those who achieved the endpoint 'decrease of diseased nail' were 40% higher (P < 0.05). CONCLUSION: Ciclopirox 8% hydrolacquer is more active than reference ciclopirox nail lacquer in the treatment of onychomycosis.

Proactive treatment of atopic dermatitis in adults with 0.1% tacrolimus ointment.

BACKGROUND: Long-term treatment for atopic dermatitis (AD) using low dose, intermittent, topical anti-inflammatory agents may control acute disease and prevent relapses. This 12-month, European, multicentre, randomized study investigated whether the proactive use of 0.1% tacrolimus ointment applied twice weekly can keep AD in remission and reduce the incidence of disease exacerbations (DE). METHODS: During the initial open-label period, 257 adults with AD applied 0.1% tacrolimus ointment twice daily (b.i.d.) for up to 6 weeks to affected areas. When an Investigator Global Assessment (IGA) score of < or =2 was achieved, the patient entered the disease control period (DCP) and was randomized to either proactive tacrolimus (n = 116) or vehicle ointment (n = 108) twice weekly for 12 months. Exacerbations were treated with 0.1% tacrolimus ointment b.i.d. until an IGA < or =2 was regained, then randomized treatment was restarted. The primary endpoint was the number of DEs during the DCP that required a substantial therapeutic intervention. RESULTS: Proactive tacrolimus 0.1% ointment application significantly reduced the number of DEs requiring substantial therapeutic intervention (median difference 2; P < 0.001; Wilcoxon rank sum test), the percentage of DE treatment days (median difference: 15.2%; P < 0.001; Wilcoxon rank sum test) and increased the time to first DE (median 142 vs 15 days; P < 0.001; stratified log-rank test). The adverse event profile was similar for the two treatment approaches. CONCLUSION: A 12-month, twice weekly proactive tacrolimus ointment application was an effective treatment in most study patients which prevented, delayed and reduced the occurrence of AD exacerbations.

Proactive disease management with 0.03% tacrolimus ointment for children with atopic dermatitis: results of a randomized, multicentre, comparative study.

BACKGROUND: Long-term treatment for atopic dermatitis (AD) using low-dose, intermittent, topical anti-inflammatory agents may control acute disease and prevent exacerbations. OBJECTIVES: This 12-month, European, multicentre, randomized study investigated if proactive, twice-weekly application of 0.03% tacrolimus ointment can keep AD in remission and reduce the incidence of disease exacerbation (DE) in children. PATIENTS AND METHODS: During the initial open-label period, 267 children with AD applied 0.03% tacrolimus ointment twice daily for up to 6 weeks to all affected areas. When an Investigator Global Assessment (IGA) score of