Paneth cell α-defensins HD-5 and HD-6 display differential degradation into active antimicrobial fragments.

Antimicrobial peptides, in particular α-defensins expressed by Paneth cells, control microbiota composition and play a key role in intestinal barrier function and homeostasis. Dynamic conditions in the local microenvironment, such as pH and redox potential, significantly affect the antimicrobial spectrum. In contrast to oxidized peptides, some reduced defensins exhibit increased vulnerability to proteolytic degradation. In this report, we investigated the susceptibility of Paneth-cell-specific human α-defensin 5 (HD-5) and -6 (HD-6) to intestinal proteases using natural human duodenal fluid. We systematically assessed proteolytic degradation using liquid chromatography-mass spectrometry and identified several active defensin fragments capable of impacting bacterial growth of both commensal and pathogenic origins. Of note, incubation of mucus with HD-5 resulted in 255-8,000 new antimicrobial combinations. In contrast, HD-6 remained stable with consistent preserved nanonet formation. In vivo studies demonstrated proof of concept that a HD-5 fragment shifted microbiota composition (e.g., increases of Akkermansia sp.) without decreasing diversity. Our data support the concept that secretion of host peptides results in an environmentally dependent increase of antimicrobial defense by clustering in active peptide fragments. This complex clustering mechanism dramatically increases the host's ability to control pathogens and commensals. These findings broaden our understanding of host modulation of the microbiome as well as the complexity of human mucosal defense mechanisms, thus providing promising avenues to explore for drug development.

Stable carbon and nitrogen isotopes explain methylmercury concentrations in stream food webs of Lake George, New York (USA).

Mercury has been studied extensively in lakes due to health risks associated with the consumption of contaminated fish, while stream ecosystems have received less attention. To better understand mercury bioavailability in the lower food web of streams, we collected macroinvertebrates (predators and detritivore) along with autochthonous (epilithic algae) and allochthonous (leaf litter) basal resources in eight streams entering Lake George. Samples were analyzed for methylmercury (MeHg), total mercury, and carbon and nitrogen isotopes (δ13C & δ15N) to determine how mercury concentrations in basal resources, biomagnification rates, and environmental factors (watershed characteristics and water chemistry) effected MeHg concentrations in predatory macroinvertebrates. While biomagnification rates, calculated as trophic magnification slope, explained between 68% and 98% of MeHg variability within a stream food web, the range was small (0.310-0.387) resulting in the biotic components following a consistent pattern of increasing MeHg among streams. The stream order was negatively related to basin slope for all biotic components and explained 70% of MeHg variability in predatory macroinvertebrates. Methylmercury concentrations were significantly and negatively related to δ13C in predators, epilithic algae, and leaf litter. We believe the biofilms on leaf litter utilized bacterial-respired carbon dioxide decreasing δ13C (<-28‰) and increasing MeHg while epilithic algal δ13C increased due to enhanced primary production resulting in biodilution of MeHg. Methylmercury in basal resources responded to δ13C similarly but through different processes. Our findings show shallow slopes elevate MeHg in basal resources and explain most of the predator MeHg variation among streams with little influence of biomagnification rates.

[Treatment of a terbinafine-resistant trichophyton mentagrophytes type VIII]. / Therapie eines Terbinafin-resistenten Trichophyton mentagrophytes Typ VIII.

This article reports on a patient suffering from terbinafine-resistant tinea corporis acquired in Asia. Trichophyton mentagrophytes type VIII was first isolated in India. In the past few years, it has gained clinical relevance by causing terbinafine-resistant tinea corporis and cruris. Therefore, in cases of recalcitrant tinea in persons returning from Asia, systemic itraconazole should be started. Specially formulated itraconazole enables high bioavailability despite lower dosage.

Recommendations for rosacea diagnosis, classification and management: update from the global ROSacea COnsensus 2019 panel.

BACKGROUND: A transition from a subtyping to a phenotyping approach in rosacea is underway, allowing individual patient management according to presenting features instead of categorization by predefined subtypes. The ROSacea COnsensus (ROSCO) 2017 recommendations further support this transition and align with guidance from other working groups. OBJECTIVES: To update and extend previous global ROSCO recommendations in line with the latest research and continue supporting uptake of the phenotype approach in rosacea through clinical tool development. METHODS: Nineteen dermatologists and two ophthalmologists used a modified Delphi approach to reach consensus on statements pertaining to critical aspects of rosacea diagnosis, classification and management. Voting was electronic and blinded. RESULTS: Delphi statements on which the panel achieved consensus of ≥ 75% voting 'Agree' or 'Strongly agree' are presented. The panel recommends discussing disease burden with patients during consultations, using four questions to assist conversations. The primary treatment objective should be achievement of complete clearance, owing to previously established clinical benefits for patients. Cutaneous and ocular features are defined. Treatments have been reassessed in line with recent evidence and the prior treatment algorithm updated. Combination therapy is recommended to benefit patients with multiple features. Ongoing monitoring and dialogue should take place between physician and patients, covering defined factors to maximize outcomes. A prototype clinical tool (Rosacea Tracker) and patient case studies have been developed from consensus statements. CONCLUSIONS: The current survey updates previous recommendations as a basis for local guideline development and provides clinical tools to facilitate a phenotype approach in practice and improve rosacea patient management. What's already known about this topic? A transition to a phenotype approach in rosacea is underway and is being recommended by multiple working groups. New research has become available since the previous ROSCO consensus, necessitating an update and extension of recommendations. What does this study add? We offer updated global recommendations for clinical practice that account for recent research, to continue supporting the transition to a phenotype approach in rosacea. We present prototype clinical tools to facilitate use of the phenotype approach in practice and improve management of patients with rosacea.

The hip fracture surgery in elderly patients (HIPELD) study to evaluate xenon anaesthesia for the prevention of postoperative delirium: a multicentre, randomized clinical trial.

BACKGROUND: Postoperative delirium occurs frequently in elderly hip fracture surgery patients and is associated with poorer overall outcomes. Because xenon anaesthesia has neuroprotective properties, we evaluated its effect on the incidence of delirium and other outcomes after hip fracture surgery. METHODS: This was a phase II, multicentre, randomized, double-blind, parallel-group, controlled clinical trial conducted in hospitals in six European countries (September 2010 to October 2014). Elderly (≥75yr-old) and mentally functional hip fracture patients were randomly assigned 1:1 to receive either xenon- or sevoflurane-based general anaesthesia during surgery. The primary outcome was postoperative delirium diagnosed through postoperative day 4. Secondary outcomes were delirium diagnosed anytime after surgery, postoperative sequential organ failure assessment (SOFA) scores, and adverse events (AEs). RESULTS: Of 256 enrolled patients, 124 were treated with xenon and 132 with sevoflurane. The incidence of delirium with xenon (9.7% [95% CI: 4.5 -14.9]) or with sevoflurane (13.6% [95% CI: 7.8 -19.5]) were not significantly different (P=0.33). Overall SOFA scores were significantly lower with xenon (least-squares mean difference: -0.33 [95% CI: -0.60 to -0.06]; P=0.017). For xenon and sevoflurane, the incidence of serious AEs and fatal AEs was 8.0% vs 15.9% (P=0.05) and 0% vs 3.8% (P=0.06), respectively. CONCLUSIONS: Xenon anaesthesia did not significantly reduce the incidence of postoperative delirium after hip fracture surgery. Nevertheless, exploratory observations concerning postoperative SOFA-scores, serious AEs, and deaths warrant further study of the potential benefits of xenon anaesthesia in elderly hip fracture surgery patients. CLINICAL TRIAL REGISTRATION: EudraCT 2009-017153-35; ClinicalTrials.gov NCT01199276.

Fungal sensing of host environment.

To survive inside a host, fungi have to adapt to a changing and often hostile environment and therefore need the ability to recognize what is going on around them. To adapt to different host niches, they need to sense external conditions such as temperature, pH and to recognize specific host factors. The ability to respond to physiological changes inside the host, independent of being in a commensal, pathogenic or even symbiotic context, implicates mechanisms for sensing of specific host factors. Because the cell wall is constantly in contact with the surrounding, fungi express receptors on the surface of their cell wall, such as pheromone receptors, which have important roles, besides mediating chemotropism for mating. We are not restricting the discussion to the human host because the receptors and mechanisms used by different fungal species to sense their environment are often similar even for plant pathogens. Furthermore, the natural habitat of opportunistic pathogenic fungi with the potential to cause infection in a human host is in soil and on plants. While the hosts' mechanisms of sensing fungal pathogens have been addressed in the literature, the focus of this review is to fill the gap, giving an overview on fungal sensing of a host-(ile) environment. Expanding our knowledge on host-fungal interactions is extremely important to prevent and treat diseases of pathogenic fungi, which are important issues in human health and agriculture but also to understand the delicate balance of fungal symbionts in our ecosystem.

Updating the diagnosis, classification and assessment of rosacea: recommendations from the global ROSacea COnsensus (ROSCO) panel.

BACKGROUND: Rosacea is currently diagnosed by consensus-defined primary and secondary features and managed by subtype. However, individual features (phenotypes) can span multiple subtypes, which has implications for clinical practice and research. Adopting a phenotype-led approach may facilitate patient-centred management. OBJECTIVES: To advance clinical practice by obtaining international consensus to establish a phenotype-led rosacea diagnosis and classification scheme with global representation. METHODS: Seventeen dermatologists and three ophthalmologists used a modified Delphi approach to reach consensus on statements pertaining to critical aspects of rosacea diagnosis, classification and severity evaluation. All voting was electronic and blinded. RESULTS: Consensus was achieved for transitioning to a phenotype-based approach to rosacea diagnosis and classification. The following two features were independently considered diagnostic for rosacea: (i) persistent, centrofacial erythema associated with periodic intensification; and (ii) phymatous changes. Flushing, telangiectasia, inflammatory lesions and ocular manifestations were not considered to be individually diagnostic. The panel reached agreement on dimensions for phenotype severity measures and established the importance of assessing the patient burden of rosacea. CONCLUSIONS: The panel recommended an approach for diagnosis and classification of rosacea based on disease phenotype.

Rosacea treatment update: recommendations from the global ROSacea COnsensus (ROSCO) panel.

BACKGROUND: Rosacea is currently treated according to subtypes. As this does not adequately address the spectrum of clinical presentation (phenotypes), it has implications for patient management. The ROSacea COnsensus panel was established to address this issue. OBJECTIVES: To incorporate current best treatment evidence with clinical experience from an international expert panel and establish consensus to improve outcomes for patients with rosacea. METHODS: Seventeen dermatologists and three ophthalmologists reached consensus on critical aspects of rosacea treatment and management using a modified Delphi approach. The panel voted on statements using the responses 'strongly disagree', 'disagree', 'agree' or 'strongly agree'. Consensus was defined as ≥ 75% 'agree' or 'strongly agree'. All voting was electronic and blinded. RESULTS: The panel agreed on phenotype-based treatments for signs and symptoms presenting in individuals with rosacea. First-line treatments were identified for individual major features of transient and persistent erythema, inflammatory papules/pustules, telangiectasia and phyma, underpinned by general skincare measures. Multiple features in an individual patient can be simultaneously treated with multiple agents. If treatment is inadequate given appropriate duration, another first-line option or the addition of another first-line agent should be considered. Maintenance treatment depends on treatment modality and patient preferences. Ophthalmological referral for all but the mildest ocular features should be considered. Lid hygiene and artificial tears in addition to medications are used to treat ocular rosacea. CONCLUSIONS: Rosacea diagnosis and treatment should be based on clinical presentation. Consensus was achieved to support this approach for rosacea treatment strategies.

Systemic therapy of ocular and cutaneous rosacea in children.

BACKGROUND: In paediatric rosacea, ocular symptoms are often predominant. Literature about systemic therapy of paediatric ocular rosacea is sparse, though. OBJECTIVE: Analysis of children with ocular rosacea treated systemically, particularly addressing remission and recurrence rates. METHODS: Retrospective study reviewing the medical records of children with ocular rosacea treated with systemic antibiotic therapy. Nine of 19 patients were chosen for detailed analysis. To our knowledge, this is the first study in paediatric ocular rosacea requiring systemic therapy with a larger patient group and a longer follow-up (mean follow-up = 30.2 months). RESULTS: 17 patients (89.5%) suffered from blepharitis, 15 patients (78.9%) from conjunctivitis, twelve patients (63.2%) from chalazia/styes and nine female patients (47.4%) from corneal involvement. We used erythromycin (n = 9) or roxithromycin (n = 1) in patients younger than 8 years and doxycycline (n = 8) or minocycline (n = 1) in patients older than 8 years. Seven of nine patients treated with erythromycin, one of eight patients treated with doxycycline and the patient treated with minocycline achieved a complete remission of ocular and cutaneous symptoms. Two of nine patients treated with erythromycin, seven of eight patients treated with doxycycline and the patient treated with roxithromycin achieved a partial remission. Relapses occurred in the patient treated with minocycline (cutaneous), two of eight patients treated with doxycycline (ocular and cutaneous) and one of nine patients treated with erythromycin (cutaneous). CONCLUSION: To achieve a complete remission of cutaneous and ocular rosacea, a long-term anti-inflammatory treatment of at least 6 months is necessary. The relapse rates seem to be lower than in adults especially in the patients treated with erythromycin.

Dual anti-inflammatory and anti-parasitic action of topical ivermectin 1% in papulopustular rosacea.

BACKGROUND: Recently, therapy of rosacea with inflammatory lesions (papulopustular) has improved substantially with the approval of topical ivermectin 1% cream. It is assumed to have a dual mode of action with anti-inflammatory capacities and anti-parasitic effects against Demodex, which however has not yet been demonstrated in vivo. AIM: To find scientific rationale for the dual anti-inflammatory and anti-parasitic mode of action of topical ivermectin 1% cream in patients with rosacea. METHODS: A monocentric pilot study was performed including 20 caucasion patients with moderate to severe rosacea, as assessed by investigator global assessment (IGA score ≥3) and a Demodex density ≥15/cm2 . Patients were treated with topical ivermectin 1% cream once daily (Soolantra® ) for ≥12 weeks. The density of Demodex mites was assessed with skin surface biopsies. Expression of inflammatory and immune markers was evaluated with RT-PCR and by immunofluorescence staining. RESULTS: The mean density of mites was significantly decreased at week 6 and week 12 (P < 0.001). The gene expression levels of IL-8, LL-37, HBD3, TLR4 and TNF-α were downregulated at both time points. Reductions in gene expression were significant for LL-37, HBD3 and TNF-α at both follow-up time points and at week 12 for TLR4 (all P < 0.05). Reduced LL-37 expression (P < 0.05) and IL-8 expression were confirmed on the protein level by immunofluorescence staining. All patients improved clinically, and 16 of 20 patients reached therapeutic success defined as IGA score ≤1. CONCLUSION: Topical ivermectin 1% cream acts by a dual, anti-inflammatory and anti-parasitic mode of action against rosacea by killing Demodex spp. in vivo, in addition to significantly improving clinical signs and symptoms in the skin.

A multicentre, randomized, single-blind, parallel-group study comparing the efficacy and tolerability of benzoyl peroxide 3%/clindamycin 1% with azelaic acid 20% in the topical treatment of mild-to-moderate acne vulgaris.

BACKGROUND: Mild-to-moderate acne vulgaris is treated with a range of mono- and combination therapies; however, clinical evidence is still required to optimize treatment recommendations. OBJECTIVE: To compare the efficacy, tolerability and safety of a combination of benzoyl peroxide 3% and clindamycin 1% (BPO + CLN) with azelaic acid 20% (AzA) for the topical treatment of mild-to-moderate acne vulgaris. METHOD: This was a randomized, assessor-blinded, parallel-group, multicentre study conducted in Germany. Patients with a confirmed diagnosis of acne vulgaris, aged 12-45 years, were randomized 1 : 1 to once-daily BPO + CLN gel or twice-daily AzA cream for up to 12 weeks. The primary endpoint was the percentage change in inflammatory lesions from baseline at Week 4. Secondary endpoints included total and inflammatory lesion counts and tolerability assessments. For selected secondary endpoints, inductive statistical analysis was performed post hoc. Patient safety was assessed by adverse event (AE) monitoring. RESULTS: Efficacy was assessed in the modified intent-to-treat (mITT) population [patients using ≥1 dose of study medication (ITT), plus baseline and ≥1 post-baseline lesion count (n = 215)]. There was a statistically significant difference in the primary endpoint, with a median decrease of -52.6% for BPO + CLN (n = 107) vs.-38.8% for AzA (n = 108; P = 0.0004). There was also a greater difference in secondary lesion endpoints at Week 12, with a median decrease in inflammatory lesions of -78.8% and -65.3% and total lesions of -69.0% and -53.9% with BPO + CLN and AzA, respectively (both P < 0.0001). Tolerability was acceptable for both treatments. Overall, 55.6% (BPO + CLN) and 69.7% (AzA) of patients reported treatment-emergent AEs, and 15.7% and 35.8% of patients experienced application site reactions with BPO + CLN (24 events; 17 patients) and AzA (60 events; 39 patients) treatment, respectively (ITT population). CONCLUSION: BPO + CLN demonstrated greater efficacy than AzA in the treatment of mild-to-moderate acne vulgaris and has a positive tolerability and safety profile.

[Pathogenesis, clinical picture, and current therapy of rosacea]. / Pathogenese, Klinik und aktuelle Therapie der Rosazea.

Rosacea is a common chronic inflammatory disease, especially in patients with fair skin and positive family history. Typical locations are forehead, nose, cheeks and chin; the periorbital region is usually not involved. Clinical features can be very heterogeneous. Besides different subtypes (erythematotelangiectatic rosacea, papulopustular rosacea, phymatous rosacea), which often overlap, various special forms of rosacea exist. Up to 60% of patients with cutaneous rosacea suffer from ocular rosacea. In Germany, brimonidine, metronidazol, azelaic acid, and ivermectin are approved for topical therapy of rosacea; for systemic therapy, doxycycline at a subantimicrobial dose (40 mg/day) is the only approved substance. In case of resistance to this therapy, contraindications or side effects, various alternative therapies are available, however off-label.

[Requirements for mycological diagnostics in accordance with the guideline of the German Medical Association for quality assurance of medical laboratory tests]. / Anforderungen für die mykologische Diagnostik entsprechend der Richtlinie der Bundesärztekammer (Rili-BÄK) zur Qualitätssicherung laboratoriumsmedizinischer Untersuchungen.

The ability of recognizing various clinical manifestations of mucocutaneous mycosis, making a diagnosis, and establishing a treatment is part of a dermatologist's daily routine. However, due to the fact that clinical manifestations, laboratory diagnostics, and treatment are performed in one hand, laboratory findings are properly classified and interpreted. Since new binding guidelines of the German Medical Association on quality assurance measures in medical laboratory testing came into force, there is much concern among dermatologists of how to comply with these new regulations. It is the intention of the authors to help our readers to implement these new rules in order to make sure that mycological diagnostics continue to be part of a dermatologist's professional work.

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.

Pathogenesis and clinical presentation of rosacea as a key for a symptom-oriented therapy.

Rosacea is a common chronic inflammatory skin disorder that typically occurs in adults and affects the face. Synonyms of rosacea include "acne rosacea", "couperose" and "facial erythrosis", in German also "Kupferfinne" and "Rotfinne". The disorder is characterised by a chronic and flaring course and is caused by a genetically predisposed, multifactorial process. A higher incidence is seen in people with fair skin and a positive family history. The characteristic rosacea symptoms manifest primarily, but not exclusively centrofacially, with forehead, nose, chin and cheeks significantly affected. Based on the various main symptoms a classification of the individual clinical pictures can be performed. However, a classification often does not reflect the clinical reality, since the various symptoms commonly coexist. The present review provides an introduction on pathogenesis and clinical manifestations of rosacea and prefers a symptom-oriented therapy approach.

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.

Pathogenese und Klinik der Rosazea als Schlüssel für eine symptomorientierte Therapie.

Rosazea ist eine häufige chronisch-entzündliche Hauterkrankung, die typischerweise bei Erwachsenen vorkommt und das Gesicht betrifft. Synonyme der Rosazea sind Acne rosacea, Kupferfinne, Rotfinne, Couperose und Rosacea. Die Erkrankung ist durch einen chronischen und schubartigen Verlauf gekennzeichnet und wird durch ein genetisch prädisponiertes, multifaktorielles Geschehen bedingt. Ein vermehrtes Auftreten wird bei hellem Hauttyp und positiver Familienanamnese verzeichnet. Die charakteristischen Rosazea-Symptome manifestieren sich vorwiegend, aber nicht ausschließlich zentrofazial, wobei Stirn, Nase, Kinn und die Wangen maßgeblich betroffen sind. Dabei werden unterschiedliche Hauptsymptome voneinander unterschieden, anhand derer eine Klassifikation der verschiedenen klinischen Bilder vorgenommen werden kann. Eine Klassifizierung wird oftmals jedoch nicht der klinischen Realität gerecht, da die verschiedenen Symptome häufig gemeinsam auftreten. Diese Übersichtarbeit führt in die Pathogenese und Klinik der Rosazea ein und plädiert für einen symptomorientierten Therapieansatz.

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.

Comparison of user-friendliness and treatment cost of Loceryl® vs. Ciclopoli®--a patient's perspective.

Topical monotherapy is a valid therapeutic approach in onychomycosis. Due to its lengthy course and its non-reimbursed product status, cost and compliance are important issues and non-pharmacological properties such as over-the-counter price and ease of use should be considered when deciding which product to recommend. We investigated surrogate parameters for patient-friendliness and treatment cost in Germany in a questionnaire-based prospective, comparative, intra-individual, open-label trial of the two common topical antifungal nail lacquers Loceryl(®) (amorolfine 5%) and Ciclopoli(®) (ciclopirox 8%) in eight patients with clinically diagnosed onychomycosis. The 2.5 ml bottle of Loceryl(®) covered a treatment period of 308 days, resulting in treatment costs of €0.10 per day in comparison to the 3.3 ml bottle of Ciclopoli(®), covering 127 days at €0.21 per day, given once-daily application for Ciclopoli(®) and once-weekly application for Loceryl(®) in accordance with regulatory approval. Six out of eight patients favoured the Loceryl(®) treatment regimen. Furthermore, four out of eight patients found Loceryl(®) easier to apply, whereas three preferred Ciclopoli(®). In total, seven out of eight stated a clear preference for Loceryl(®) over Ciclopoli(®). Loceryl(®) therapy is less expensive and less time-consuming. The therapeutic period that can be covered is longer and more patients stated a clear preference for Loceryl(®) in comparison to Ciclopoli(®). The differences are statistically significant, underlining probable clinical relevance.