Dermatomycological guidelines: 10 years of experience in Germany.

Since the mid-1990s of the last century, dermatomycological guidelines have been prepared and published in Germany. This has been achieved by a group of experts encompassing leading representatives of Deutschsprachige Mykologische Gesellschaft, Deutsche Dermatologische Gesellschaft as well as Berufsverband Deutscher Dermatologen. Preparation of guidelines is based on a defined procedure. The first draft is prepared by one to three experts and then forwarded to all members of the working group for further discussion and improvement. This can be by way of either conventional mail or electronic mail. All aspects turning up in the process are reflected by the head of the working group and these aspects are used to prepare another version, which is again distributed to all members of the working group. Following up to three or four pertinent rounds of optimisation, a final version based on general consensus will be available at the end. All guidelines are subject to adaptation in a period of 3-5 years at the latest or if needed even earlier.

Onychomycosis.

The guideline on onychomycosis, as passed by the responsible German medical societies, is presented in the present study.

Tinea capitis: ringworm of the scalp.

The guideline tinea capitis, as passed by three German medical societies, is presented in the present study.

Prior immunisation of patients with malignant melanoma with vaccinia or BCG is associated with better survival. An European Organization for Research and Treatment of Cancer cohort study on 542 patients.

There is increasing evidence that infections and vaccinations play an important role in the normal maturation of the immune system. It was therefore of interest to determine whether these immune events also affect the prognosis of melanoma patients. A cohort study of 542 melanoma patients in six European countries and Israel was conducted. Patients were followed up for a mean of 5 years and overall survival was recorded. Biometric evaluations included Kaplan-Meier estimates of survival over time and Hazard Ratios (HRs), taking into account all known prognostic factors. During the follow-up between 1993 and 2002, 182 of the 542 patients (34%) died. Survival curves, related to Breslow's thickness as the most important prognostic marker, were in accordance with those observed in previous studies where the cause of death was known to be due to disseminated melanoma. In a separate analysis of patients, vaccinated with vaccinia or Bacille Calmette-Guerin (BCG), HRs and the corresponding 95% Confidence Intervals (CIs) were 0.52 (0.34-0.79) and 0.69 (0.49-0.98), respectively. Joint analyses yielded HRs (and 95% CIs) of 0.55 (0.34-0.89) for patients vaccinated with vaccinia, 0.75 (0.30-1.86) with BCG, and 0.41 (0.25-0.69) with both vaccines. In contrast, infectious diseases occurring before the excision of the tumour had little, or, at the most, a minor influence on the outcome of the melanoma patients. These data reveal, for the first time, that vaccination with vaccinia in early life significantly prolongs the survival of patients with a malignant tumour after initial surgical management. BCG vaccination seems to have a similar, although weaker, effect. The underlying immune mechanisms involved remain to be determined.

[Modern antimycotics. What the treating physician needs to know]. / Moderne Antimykotika. Was der behandelnde Arzt darüber wissen sollte.

The treatment of dermatophytoses is a complex process influenced by the properties of the antimycotic and the causative agent as well as by patient-related factors. Both the minimal inhibition concentration and the drug concentration in the infected tissue influence treatment success. Dermatophytes can be present as arthrospores in the skin, nails or hair. Non-proliferating dermatophytes (arthrospores) are less susceptible to antimycotics than proliferating ones, particularly to antibiotics which act through the inhibition of fungal ergosterol synthesis. Non-proliferating dermatophytes do not synthesize ergosterol, a essential component of fugal cell membranes. Also, dermatophytes accumulating in hollow spaces mostly in the nail plate, cannot be reached by antimycotics. The concentration of terbinafine and itraconazole is very high in sebum. This is of importance in the treatment of dermatophytoses localized to in the stratum corneum and in or around the hair. Preadolescent children do not have functioning sebaceous glands; this explains the difficulties in the treatment of pediatric tinea capitis.

Guideline vulvovaginal candidosis: guideline of the German Dermatological Society, the German Speaking Mycological Society and the Working Group for Infections and Infectimmunology of the German Society for Gynecology and Obstetrics.

The Guideline vulvovaginal candidosis, as passed by three German medical societies, is presented.

Oral vinorelbine in combination with cisplatin: a novel active regimen in advanced non-small-cell lung cancer.

BACKGROUND: A phase II trial of alternating i.v. and oral vinorelbine in combination with cisplatin was designed to determine the response rate, safety profile, progression-free survival, overall survival and quality of life (QoL) in advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Fifty-six chemotherapy-naïve patients received cisplatin 100 mg/m(2) and i.v. vinorelbine 25 mg/m(2) on day 1, followed by oral vinorelbine 60 mg/m(2) on days 8, 15 and 22, every 28 days. RESULTS: After an independent review, the response rate was 33% [95% confidence interval (CI) 20% to 46%]. Median progression-free and overall survival were 5.5 months (95% CI 3.7-6.4) and 8.9 months (95% CI 8.8-11.7), respectively. The most frequent hematological toxicities were neutropenia (grade 3-4 in 73% of patients) and anemia (grade 3-4 in 11% of patients). Grade 3-4 infections and non-hematological toxicities occurred occasionally. QoL for lung cancer related symptoms was stable or improved. CONCLUSIONS: The efficacy and safety of the alternating vinorelbine schedule (i.v. on day 1, oral on days 8, 15 and 22) in combination with cisplatin in advanced NSCLC are similar to those of the standard regimen using exclusively i.v. vinorelbine, whereas ease of administration and patient comfort may favor the novel approach.

Impact of vaccinations and infectious diseases on the risk of melanoma--evaluation of an EORTC case-control study.

A significant correlation between a reduced risk of melanoma and BCG and vaccinia vaccination in early childhood or infectious diseases later in life has already been reported from the FEBrile Infections and Melanoma (FEBIM) multicentre case-control study. This correlation is further evaluated in this study based on 603 incident cases of malignant melanoma and 627 population controls in six European countries and Israel by means of a joint analysis of the influence of vaccinations and infectious diseases. In addition, the previously unconsidered impact of influenza vaccinations is evaluated for the whole study population. The strong effects of the frequently given BCG and vaccinia vaccinations in early childhood, as well as of uncommon previous severe infectious diseases, were apparently not cumulative. With the Odds Ratio (OR) being set at 1 in the absence of vaccinations and infectious diseases, the OR dropped to 0.37 (95% Confidence Interval (CI): 0.10-1.42) when subjects had experienced one or more severe infectious diseases, associated with a fever of > 38.5 degrees C, and had not been vaccinated with BCG or vaccinia. The OR was 0.29 (CI: 0.15-0.57) in those who had had a severe infectious disease and were vaccinated with either BCG or vaccinia and 0.33 (CI: 0.17-0.65) for those with 1 or more severe infectious diseases and who had received both vaccinations. We conclude that both vaccinations as well as previous episodes of having a severe infectious disease induced the same protective mechanism with regards to the risk of melanoma. Because of a 'masking effect' by the vaccinia vaccination, the protective effect of the BCG vaccination and of certain infectious diseases against cancer has remained undetected. The vaccinations contributed more to the protection of the population than a previous episode of having an infectious disease. In view of the termination of vaccinations with vaccinia in all countries and of BCG in many of them, these findings call for a re-evaluation of vaccination strategies.

[The change of dermatophyte spectrum in dermatomycoses]. / Zur Veränderung des Dermatophytenspektrums bei dermatologisch relevanten Erkrankungen.

The spectrum of dermatophytes out of mycotic skin lesions had changed in last 70 years. Before the Second World War in Germany Microsporum audouinii and Epidermophyton floccosum held the first position, since the fifties of last century Trichophyton rubrum is the most frequently isolated dermatophyte accounting for 80-90% of the strains, followed by T. mentagrophytes. This development is typical for Central and North Europe and is connected with the increase in the incidence of tinea pedis. In contrast to this, in Southern Europe and in Arab countries zoophilic dermatophytes, such as M. canis and T. verrucosum, are the most frequently isolated dermatophytes. An analysis of the frequency and distribution of tinea pedis in different occupations and the route of infection is also reported. The epidemiologic findings are contrary to the assumption that patients are genetically predisposed to T. rubrum infection in a dominant autosomal pattern.

Survival probabilities and hazard functions of malignant melanoma in Germany 1972-1996, an analysis of 10433 patients. Evolution of gender differences and malignancy.

The evaluation of the impact of prevention activities on the course of survival in conjunction with the individual hazard rate of dying is described using data from a follow-up study of 10433 melanoma patients during three observation periods (1972-1980, 1981-1988, 1989-1996). Kaplan-Meier survival curves combined with hazard functions were calculated. At all observation periods, survival of men was lower compared with women and their maximum dying risk was earlier (70 versus 100 months after removal of the primary tumour). In 1989-1996, differences in the survival rates were approximately halved compared with those for 1972-1980 or 1981-1988, respectively. This improvement was predominantly seen in young men. There was a lower survival rate of men compared with women with identical thickness categories. The maximum dying risk for those men with tumours >4 mm peaked at approximately 60 months, the other thickness categories showing a lower and later maximum; in women, the maximum dying risk for tumours >4 mm was also seen at approximately 60 months, but less pronounced. Over time, the influence of Breslow thickness on the survival rates remained constant in women; in men, with the exception of thick tumours, there was a trend towards a better survival. Melanoma awareness campaigns conducted in Germany since the late 1980s have resulted in a trend towards a remarkable increase of thin tumours in recent years, whereas the number of new cases with thick tumours has remained constant.

[History of Medical Mycology in the former German Democratic Republic]. / Zur Geschichte der medizinischen Mykologie in der ehemaligen DDR.

After the Second World War the development of medical mycology in Germany had taken a very different course in the east and west parts depending on the political division. In this respect our contribution deals with the situation in the former German Democratic Republic. Efficient mycological centres were founded step by step almost in all medical universities on the basis of the mycological laboratories in dermatological hospitals competent for diagnostic work, but also for teaching and scientific research. In this context biologists were the main stay of mycology, they finally were integrated to the same degree in the universities like physicians. The effectiveness of the Gesellschaft für Medizinische Mykologie der DDR (GMM), its board of directors and its working groups as well as the topics of human and animal mycology during this period are described. Especially the merger of the GMM with the Deutschsprachige Mykologische Gesellschaft after the reunification of Germany without problems and the kind co-operation of Prof. Dr. Johannes Müller during this procedure are emphasized.

A multicenter, open-label study of the efficacy and safety of ciclopirox nail lacquer solution 8% for the treatment of onychomycosis in patients with diabetes.

This multicenter, open-label, uncontrolled, noncomparative, observational, postmarketing study assessed the efficacy and safety of ciclopirox nail lacquer solution 8% in 3666 patients for the treatment of onychomycosis. Results of an analysis in a subset of 215 (5.9%) patients with diabetes are summarized here. Patients applied ciclopirox nail lacquer once daily to affected toenails and fingernails for 6 months. Efficacy parameters included the decrease from baseline of the affected area of the nail. Physicians rated the level of onychomycosis at 3 months and the efficacy of ciclopirox nail lacquer at 6 months. Treatment with ciclopirox nail lacquer reduced the mean affected nail area from 64.3% at baseline to 41.2% at 3 months and 25.7% at 6 months. At 3 months, physicians rated onychomycosis as improved in 88.7% of patients. unchanged in 9.8%, and worse in 1.5%. The efficacy of ciclopirox nail lacquer was good in 62.0% of patients, satisfactory in 23.9%, and unsatisfactory in 14.1%. Adverse events were mild to moderate, with no serious events reported. Ciclopirox nail lacquer is safe and effective for the topical treatment of onychomycosis in patients with diabetes and produced results similar to those observed in the general population.

[Mortality of invasive malignant cutaneous melanoma. A review with special consideration of gender distribution]. / Zur Sterblichkeit am kutanen invasiven malignen Melanom. Ubersicht unter besonderer Berücksichtigung der Geschlechterverteilung.

BACKGROUND AND OBJECTIVE: The final goals of malignant melanoma prevention are lowering incidence and mortality. We assessed the parameter "survival" for both men and women as the beginning point for future gender-directed prevention campaigns. We compared the periods 1972-1980, 1981-1988, 1989-1996, and determined the influence of age and of Breslow' tumor thickness on survival. PATIENTS/METHODS: We had sufficient follow-up on 10.433 patients. We calculated survival curves according to Kaplan-Meier and defined differences by the logrank test. RESULTS: At all periods of time, survival of women was higher compared with men, but with no impressive changes over time. This was especially true for younger men. The most important prognostic factor was the Breslow tumor thickness. Within all periods of time, its median was higher in men. A trend downwards for both genders could be observed with higher influence on survival in men. CONCLUSIONS: Our findings justify melanoma prevention campaigns addressed to men. Evaluation of such campaigns has to take into account an already existing upwards trend for male survival, which exceeds that of female survival.

Immunohistochemical panels for differentiating epithelial malignant mesothelioma from lung adenocarcinoma: a study with logistic regression analysis.

Immunohistochemistry provides an important indicator for differential diagnosis between pleural malignant mesothelioma and lung adenocarcinoma, which have complex therapeutic and medicolegal implications. To pinpoint a reliable, restricted panel of markers, the authors evaluated the efficacy of select commercial antibodies in a series of patients with confirmed clinicopathologic diagnosis of mesothelioma or lung adenocarcinoma with the aid of multiple logistic classification tables. Specimens of 46 mesotheliomas and 20 lung adenocarcinomas were examined with calretinin, thrombomodulin, cytokeratins (CKs) 5/6, and high-molecular weight CKs (indicators of mesothelioma), alongside MOC 31, Ber-EP4, and carcinoembryonic antigen (CEA; indicators of lung adenocarcinoma). Of the mesotheliomas, 40 of 46 (87%) were positive with calretinin, 29 of 46 (63%) with thrombomodulin, 40 of 46 (87%) with CKs 5/6, and 41 of 46 (89%) with high-weight CKs; five of 46 mesotheliomas (11%) were focally reactive with MOC 31, four of 46 (9%) with Ber-EP4, and two of 46 (4%) with CEA. Of the lung adenocarcinomas, 18 of 20 (90%) were positive with MOC 31, 20 of 20 (100%) with Ber-EP4, and 17 of 20 (85%) with CEA; and two of 20 (10%) were focally reactive with calretinin, one of 20 (5%) with thrombomodulin, none of 20 (0%) with CKs 5/6, and five of 20 (25%) with high-weight CKs. Multiple logistic modeling indicated two batteries of three antibodies permitting more than 98% overall accuracy: Ber-EP4 plus CKs 5/6 plus calretinin, and Ber-EP4 plus CKs 5/6 plus CEA.

[Epidemiology, clinic and treatment of dermatomycoses caused by zoophilic dermatophytes] . / Epidemiologie, Klinik und Therapie von Dermatomykosen durch zoophile Dermatophyten.

In the last 50 years the spectrum of agents of dermatophytoses changed. The change is remarkable especially in the case of zoophilic dermatophytes. Microsporum canis has displaced Trichophyton verrucosum. In the period from 1966 to 1970 2822 dermatophytoses were registered as occupational dermatoses in the former German Democratic Republic. In the following years the number of these diseases was continuously reduced, between 1981 and 1985 down to 995 cases. This reduction is predominantly the result of active immunoprophylaxis by means of inactivated, hydrolized vaccines, mainly by the Soviet live vaccine LTF-130. The scientific basis of this vaccination was established by Kielstein and co-workers. The treatment of Microsporum canis infection of the scalp requires the administration of systemically acting antimycotics over a long period (6-8 weeks).

[Candida in dermatology]. / Candida in der Dermatologie.

Regarding Candida in dermatology, two pathogenetic pathways must be taken into account: 1. on infection of the skin 2. immunological reactions with skin alterations as a result of Candida infection or colonization in the mouth and/or intestine. Case reports describe typical situations of napkin dermatitis, intertriginous candidosis, the intrauterine Candida infection of the foetus, Candida granuloma, Candida folliculitis and Candida paronychia. In the second part results of investigations of patients suffering from psoriasis, atopic dermatitis and urticaria are presented. There were no differences in the colonization with Candida albicans and in the level of Candida antibody titres between patients and a healthy control group.

Infections and melanoma risk: results of a multicentre EORTC case-control study. European Organization for Research and Treatment of Cancer.

Immune function plays a prominent role in the defence against cutaneous malignant melanoma and the increased risk of melanoma development during immunosuppression. Since the immune system is challenged beyond its routine activity by an infection, the effect of previous infectious diseases on the risk of melanoma may also be crucial. In a European Organization for Research and Treatment of Cancer (EORTC) case-control study performed in six European countries and Israel, we compared the history of severe infections in 603 melanoma patients with that in 627 population controls. We calculated adjusted odds ratios (ORs) to estimate the effect of infectious diseases on melanoma risk. The ORs for melanoma risk were below 1 for nearly all types of infections (except two) if body temperature was not taken into consideration, and for all infections with a body temperature above 38.5 degrees C. In the latter category significantly lowered ORs were found for pulmonary tuberculosis (0.16; 95% confidence interval [CI] 0.01-0.98), Staphylococcus aureus infections (0.54; 95% CI 0.31-0.94), sepsis (0.23; 95% CI 0.06-0.70), influenza and related infections (0.65; 95% CI 0.48-0.86) and pneumonia (0.45; 95% CI 0.27-0.73). Analysis of the cumulative influence revealed a consistent pattern of results pointing to a reduction in melanoma risk with increasing numbers of recorded infections and fever height. This apparent dose-response relationship suggests a causal association. Speculations on the underlying mechanism include a Shwartzman-like phenomenon when melanoma formation precedes the infection and/or an infection-related Th1-cell activation preventing the establishment of the tumour.