[Decision criteria and patient characteristics for patient-oriented treatment of field cancerization : Standardized algorithm for personalized treatment concepts]. / Entscheidungskriterien und Patientencharakteristika zur patientenorientierten Therapie der Feldkanzerisierung : Ein standardisierter Bewertungsalgorithmus für individuelle Behandlungskonzepte.

BACKGROUND: Actinic keratosis (AK), which frequently affects larger skin areas (field cancerization), is characterized by chronic course. Weighing therapy-specific advantages and disadvantages of field-oriented therapy for individual patients is challenging. OBJECTIVES: The main objective was the development of patient-oriented decision criteria for the pragmatic classification of field-directed AK treatment options in patients with a predisposition for field cancerization (patient types 1-3). MATERIALS AND METHODS: The development of the decision criteria and patient typology was based on a nominal respectively structured multilevel group process. The developed algorithm was then subsequently applied for the systematic evaluation of field-directed AK therapies. RESULTS: Patient-relevant criteria for the treatment decision included (among others): effectiveness, selectivity, safety, duration of therapy, cosmesis, patient preference and comorbidities. With regard to the decision criteria and patient types in which field therapy was the treatment of choice, daylight photodynamic therapy notably met the requirement profile. CONCLUSION: The definition of patient-relevant and therapy-related decision criteria in AK field therapy allows a systematic yet practice-oriented approach to classify specific treatment options and to derive individual treatment decisions.

[Terbinafine-resistant dermatophytoses and onychomycosis due to Trichophyton rubrum]. / Terbinafin-resistente Dermatophytosen und Onychomykose durch Trichophyton rubrum.

BACKGROUND: In recent years, therapy-refractory courses of dermatophytoses have increasingly become the focus of attention. The most frequent pathogens are Trichophyton (T.) rubrum and T. mentagrophytes. In addition to local therapy, first-line treatment includes terbinafine, an allylamine antifungal agent that acts by inhibiting squalene epoxidase and thus interfering with ergosterol synthesis. In refractory cases, terbinafine resistance due to point mutation in the squalene epoxidase gene has been frequently detected. OBJECTIVES: The aim is to present specific aspects in the epidemiology of dermatophytoses with terbinafine resistance and to illustrate them on the basis of four patient cases including diagnostic procedures. MATERIALS AND METHODS: A review of handbook knowledge, a selective literature search, and a review of four patient cases were performed. RESULTS: Detection of the terbinafine resistance was performed by in vitro testing using the breakpoint method as well as sequencing of the Trichophyton isolate and detection of the point mutation with amino acid substitution at position L393F or F397L of squalene epoxidase. CONCLUSION: In refractory and recurrent dermatophytoses, terbinafine resistance should be considered, especially in T. mentagrophytes and T. rubrum, and in vitro resistance testing of the dermatophyte and point mutation analysis of squalene epoxidase (SQLE) should be performed. Therapeutically, intermittent administration of itraconazole in combination with antifungal local therapy is recommended. Nevertheless, a recurrent course is to be expected and long-term therapy with itraconazole is usually necessary.

A randomized, intraindividual, non-inferiority, Phase III study comparing daylight photodynamic therapy with BF-200 ALA gel and MAL cream for the treatment of actinic keratosis.

BACKGROUND: The most effective treatment modality for actinic keratosis (AK) is photodynamic therapy (PDT). Major obstacles of PDT are the need of a special illumination device and pain accompanying the illumination. These issues may be overcome by replacing an artificial high-power light source with natural daylight for more extended illumination at lower light doses. OBJECTIVE: To determine whether BF-200 ALA (a nanoemulsion gel containing 7.8% 5-aminolaevulinic acid) is non-inferior to MAL (a cream containing 16% methyl-aminolaevulinate) in the treatment of mild-to-moderate AK with daylight PDT (dPDT). Non-inferiority of the primary efficacy variable (total lesion clearance rate per patient's side 12 weeks after PDT) is established if the mean response for BF-200 ALA is no worse than for MAL, within a statistical margin of Δ = -12.5%. METHODS: The study was performed as an intraindividual comparison with 52 patients in seven centres in Germany and Spain. Each patient received one dPDT. Results include clinical endpoints as well as 1-year follow-up results. RESULTS: Twelve weeks after a single dPDT, 79.8% of the AK lesions treated with BF-200 ALA gel and 76.5% of the lesions treated with MAL cream were completely cleared. The median of differences was 0.0 with a one-sided 97.5% CI of 0.0, establishing non-inferiority (P < 0.0001). Results for secondary efficacy parameters were in line with the primary outcome. Recurrence rates 1 year after the treatment were 19.9% for lesions treated with BF-200 ALA and 31.6% for lesions treated with MAL. Adverse reactions including pain were mostly mild and transient and identical to those previously described for dPDT. CONCLUSION: Daylight PDT of AK with BF-200 ALA is well-tolerated and non-inferior to MAL/dPDT. The study demonstrates a trend towards higher efficacies after 3 months and significantly lower recurrence rates after 1 year follow-up.

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.

A randomized, multinational, noninferiority, phase III trial to evaluate the safety and efficacy of BF-200 aminolaevulinic acid gel vs. methyl aminolaevulinate cream in the treatment of nonaggressive basal cell carcinoma with photodynamic therapy.

BACKGROUND: Basal cell carcinoma (BCC) represents the most common nonmelanoma skin cancer worldwide, affecting mainly adult, fair-skinned individuals. The World Health Organization distinguishes aggressive and nonaggressive forms, of which prototypical variants of the latter are primary nodular and superficial BCC. OBJECTIVES: To demonstrate noninferiority of BF-200 ALA (a nanoemulsion gel containing 5-aminolaevulinic acid) compared with MAL (a cream containing methyl aminolaevulinate) in the treatment of nonaggressive BCC with photodynamic therapy (PDT). Noninferiority of the primary efficacy variable (overall patient complete response 12 weeks after last PDT) would be declared if the mean response for BF-200 ALA was no worse than that for MAL, within a statistical margin of Δ = -15%. METHODS: The study was a randomized, phase III trial performed in Germany and the U.K. with ongoing 5-year follow-up. Of 281 randomized patients, 138 were treated with BF-200 ALA and 143 with MAL. Patients received two PDT sessions 1 week apart. Remaining lesions 12 weeks after the second PDT were retreated. Illumination was performed with a red light source (635 nm, 37 J cm-2 ). The results shown include clinical end points and patients' reassessment 12 months after the last PDT. The study was registered with EudraCT (number 2013-003241-42). RESULTS: Of the BF-200 ALA-treated patients, 93·4% were complete responders compared with 91·8% in the MAL group. The difference of means was 1·6, with a one-sided 97·5% confidence interval of -6·5, establishing noninferiority (P < 0·0001). The results for secondary efficacy parameters were in line with the primary outcome. Recurrence rates 12 months after the last treatment were ≤ 10%. CONCLUSIONS: Treatment of nonaggressive BCC with BF-200 ALA-PDT is highly effective and well tolerated with proven noninferiority to MAL-PDT. It demonstrates low recurrence rates after 1 year of follow-up.

A randomized, double-blind, phase III, multicentre study to evaluate the safety and efficacy of BF-200 ALA (Ameluz(®) ) vs. placebo in the field-directed treatment of mild-to-moderate actinic keratosis with photodynamic therapy (PDT) when using the BF-RhodoLED(®) lamp.

BACKGROUND: Multiple actinic keratosis (AK) lesions may arise from the cancerization of large, sun-damaged skin areas. Although photodynamic therapy (PDT) is considered the most effective therapeutic option, the efficacy and safety of field treatment of multiple AK lesions with PDT has never before been tested in a pivotal trial. OBJECTIVES: To evaluate the efficacy, safety and cosmetic outcome of BF-200 ALA (a nanoemulsion formulation containing 10% aminolaevulinic acid hydrochloride) combined with the BF-RhodoLED(®) lamp for the field-directed treatment of mild-to-moderate AK with PDT. METHODS: The study was performed as a randomized, multicentre, double-blind, placebo-controlled, parallel-group, phase III trial with BF-200 ALA and placebo in seven centres in Germany. A total of 94 patients were enrolled in this study; 87 were randomized (55 patients received BF-200 ALA, 32 received placebo). Patients received one PDT. If residual lesions remained at 3 months after treatment, PDT was repeated. Illumination was performed with the PDT lamp BF-RhodoLED (635 nm ± 9 nm) until a total light dose of 37 J cm(-2) was achieved. RESULTS: BF-200 ALA was superior to placebo with respect to patient complete clearance rate (91% vs. 22%, P < 0·0001) and lesion complete clearance rate (94·3% vs. 32·9%, P < 0·0001) after a maximum of two PDTs. The confirmatory analysis of all key secondary variables supported this superiority" should not be skipped since this is an important result. Treatment-emergent adverse events (TEAEs) were experienced by 100% of the BF-200 ALA group and 69% of the placebo group. The most commonly reported TEAEs were TEAEs of the application site. The cosmetic outcome was improved in the BF-200 ALA group compared with placebo. CONCLUSIONS: Field-directed therapy with BF-200 ALA and BF-RhodoLED lamp is highly effective and well tolerated for multiple mild-to-moderate AK lesions, providing greatly improved skin quality.

[Therapy of hypertrophic scars and keloids]. / Therapie hypertropher Narben und Keloide.

Keloids mostly occur between the ages of 10 and 30 years and grow continuously beyond the original margins of the scar. Beside the cosmetic impairment they often lead to pruritus, pain, contractures and decrease in quality of life. Advances in the understanding of the genetics and pathogenesis of hypertrophic scars and keloids have led to new therapeutic options. Nevertheless treatment remains a challenge and there is no single treatment modality which is appropriate for all types of scars. Combined approaches are becoming more widely employed as they are more effective than single treatment modalities. This article gives an overview of hypertrophic scars and keloids, their pathogenesis and recommended therapeutic approaches.

Proxy assessment of patients before and after radiotherapy for brain metastases. Results of a prospective study using the DEGRO brain module.

PURPOSE: Proxies of patients with poor performance status could give useful information about the patients' quality of life (QoL). We applied a newly developed questionnaire in a prospective QoL study of patients undergoing radiotherapy for brain metastases in order to make the first move to validate this instrument, and we compared the results with scores obtained using validated patient-completed instruments. MATERIALS AND METHODS: From January 2007 to June 2010, 166 patients with previously untreated brain metastases were recruited at 14 centers in Germany and Austria. The EORTC-QLQ-C15-PAL and the brain module BN20 were used to assess QoL in patients at the start of treatment and 3 months later. At the same time points, 141 of their proxies estimated the QoL with the new DEGRO brain module (DBM), a ten-item questionnaire rating the general condition as well as functions and impairment by symptoms in areas relevant to patients with brain metastases. RESULTS: At 3 months, 85 of 141 patients (60%) with initial response by a proxy were alive. Sixty-seven of these patients (79% of 3-month survivors) and 65 proxies completed the second set of questionnaires. After 3 months, QoL significantly deteriorated in all items of proxy-assessed QoL except headache. Correlations between self-assessed and proxy-assessed QoL were high in single items such as nausea, headache, and fatigue. CONCLUSIONS: The high correlation between self-assessment and proxy ratings as well as a similar change over time for both approaches suggest that in patients with brain metastases, proxy assessment using the DBM questionnaire can be an alternative approach to obtaining QoL data when patients are unable to complete questionnaires themselves. Our self-constructed and first applied DBM is the only highly specific instrument for patients with brain metastases, but further tests are needed for its final validation.

[Seborrheic dermatitis]. / Seborrhoisches Ekzem.

Seborrheic dermatitis is a frequent skin disorder in infancy and adulthood. It also often occurs in patients with HIV or neurologic disorders like Parkinson disease or mood disorders. It is characterized by greasy, yellow flakes or scales in areas of high sebaceous gland activity like the scalp, face, chest and upper back. Additionally, erythema and itching can be present. The etiology and pathogenesis of seborrheic dermatitis is unknown; however, the focus lies on the involvement of Malassezia yeasts or fatty acid metabolites of Malassezia, on hormones and immunologic factors. The diagnosis is usually a clinical one, based on history and the appearance and site of lesions. The therapy consists mainly of antifungal agents, corticosteroids, immunomodulators, and keratolytics. Because of the chronicity of the illness with frequent relapses, a treatment strategy in which effectiveness and potential side effects are weighed should be used.

Validation of Dermaphot(®) for the assessment of steroid-induced skin atrophy.

Currently, there are no accurate and simple methods available to measure this risk of atrophy in patients treated with topical glucocorticosteroids. In the present clinical trial, we validated a new score (Dermaphot(®) score) to assess the atrophogenic potential of glucocorticosteroids. 36 healthy adult volunteers were included in an investigator-initiated, blinded, randomized, intra-individual comparison, vehicle controlled multi-centre study. Subjects were treated in a randomized manner for 3 weeks with pimecrolimus cream 1 %, mometasone furoate (1 mg/g), clobetasol propionate 0.05 % and vehicle. In addition, ultrasound examination for skin thickness was performed. Data demonstrated a direct correlation of the achieved Dermaphot(®) score and the ultrasound thickness measurements. Our study shows that the Dermaphot(®) score can be used as a simple method to evaluate the atrophogenic potential of glucocorticosteroids. Respectively, we showed that the new score is an easy, valid and sensitive new tool for early detecting and quantifying even subclinical glucocorticosteroid-induced skin damage. We demonstrated that the score is able to differentiate the extent of skin atrophy (damage) after 3 weeks of topical glucocorticosteroid application with different levels of skin transparency and levels of telangiectasia.

[Extensive Fournier gangrene. A dermatologic emergency]. / Ausgedehnte Fournier-Gangrän. Ein Notfall in der Dermatologie.

Fournier gangrene is a necrotizing fasciitis of the perineal and genital region, which almost exclusively affects men. The cause is a polymicrobial infection associated with superficial trauma, urological diseases and operations, as well as colorectal diseases. Diabetes mellitus, alcoholism, immunosuppression and other severe illnesses are frequent co-factors. Immediate administration of systemic broad-spectrum antibiotic therapy with coverage of both gram-positive and gram-negative bacteria combined with surgical debridement and intensive medical care can lower the high mortality rate of this condition.

[Topical treatment of psoriasis: a systematic update]. / Aktuelle Aspekte der topischen Psoriasisbehandlung.

Classical topical treatment regimens in psoriasis including dithranol and corticosteroids are widely used and have been supplemented in recent years by topical vitamin D preparations, by vitamin D analogues and topical retinoids. The combination of these preparations with each other, with UV light or with systemic drugs often lead to improved effectiveness and tolerability when compared with the respective monotherapy. In private offices, the combination of calcipotriol with various corticosteroids is very commonly prescribed for patients with mild to moderate psoriasis. This combination can be sequentially applied twice daily or--in a newly introduced fixed preparation--once daily. In severe psoriasis requiring systemic treatment a concomitant effective topical treatment regimen can greatly improve the overall longtime management in affected patients.

[The treatment of keloids]. / Keloide und ihre Therapie.

Keloids are benign fibrous growths with characteristic clinical features, whose underlying pathogenic mechanisms are not fully understood. While numerous treatment approaches are available, there is little evidence for efficacy based on controlled clinical studies. Therapeutic results are often not satisfactory. The best approach employs multiple modalities appropriate for the stage of the lesion. Combining invasive methods such as cryotherapy, surgery, intralesional steroid injections, laser or radiotherapy with external or physical approaches has helped to optimize treatment efficacy. Newer clinical studies with intralesional substances such as interferons which may directly influence collagen metabolism show promising results; these substances may be valuable therapeutic additions.