Search

Purpose: To better understand the molecular mechanisms of malignant melanoma progression and metastasis, gene expression profiling was done of primary melanomas and melanoma metastases.Experimental Design: Tumor cell–specific gene expression in 19 primary melanomas and 22 melanoma metastases was analyzed using oligonucleotide microarrays after laser-capture microdissection of melanoma cells. Statistical analysis was done by random permutation analysis and support vector machines. Microarray data were further validated by immunohistochemistry and immunoblotting.Results: Overall, 308 genes were identified that showed significant differential expression between primary melanomas and melanoma metastases (false discovery rate ≤ 0.05). Significantly overrepresented gene ontology categories in the list of 308 genes were cell cycle regulation, mitosis, cell communication, and cell adhesion. Overall, 47 genes showed up-regulation in metastases. These included Cdc6, Cdk1, septin 6, mitosin, kinesin family member 2C, osteopontin, and fibronectin. Down-regulated genes included E-cadherin, fibroblast growth factor binding protein, and desmocollin 1 and desmocollin 3, stratifin/14-3-3σ, and the chemokine CCL27. Using support vector machine analysis of gene expression data, a performance of >85% correct classifications for primary melanomas and metastases was reached. Further analysis showed that subtypes of primary melanomas displayed characteristic gene expression patterns, as do thin tumors (≤1.0 mm Breslow thickness) compared with intermediate and thick tumors (>2.0 mm Breslow thickness).Conclusions: Taken together, this large-scale gene expression study of malignant melanoma identified molecular signatures related to metastasis, melanoma subtypes, and tumor thickness. These findings not only provide deeper insights into the pathogenesis of melanoma progression but may also guide future research on innovative treatments.

Supplementary Table 3 from Gene Expression Signatures for Tumor Progression, Tumor Subtype, and Tumor Thickness in Laser-Microdissected Melanoma Tissues

Supplementary Table 4 from Gene Expression Signatures for Tumor Progression, Tumor Subtype, and Tumor Thickness in Laser-Microdissected Melanoma Tissues

Supplementary Figure 1 from Gene Expression Signatures for Tumor Progression, Tumor Subtype, and Tumor Thickness in Laser-Microdissected Melanoma Tissues

Supplementary Table 1 from Gene Expression Signatures for Tumor Progression, Tumor Subtype, and Tumor Thickness in Laser-Microdissected Melanoma Tissues

Anogenital and oropharyngeal infections with human papilloma viruses (HPV) are common. Clinically manifest disease may significantly impact quality of life; the treatment of HPV-associated lesions is associated with a high rate of recurrence and invasive neoplasms, such as cervical, anal, vulvar, penile, and oropharyngeal cancers, which are characterized by significant morbidity and mortality. Vaccination against HPV is an effective and safe measure for the primary prevention of HPV-associated lesions, but immunization rates are still low in Germany. The present publication is an abridged version of the German evidence and consensus-based guideline "Vaccination recommendations for the prevention of HPV-associated lesions", which is available on the website of the German Association of the Scientific Medical Societies (AWMF). On the basis of a systematic review with meta-analyses, a representative panel developed and agreed upon recommendations for the vaccination of different populations against HPV. In addition, consensus-based recommendations were developed for specific issues relevant to everyday practice. Based on current evidence and a representative expert consensus, these recommendations are intended to provide guidance in a field in which there is often uncertainty and in which both patients and health care providers are sometimes confronted with controversial and emotionally charged points of view.

Diese Leitlinie richtet sich an Dermatologen, Ophthalmologen, HNO-Arzte, Padiater, Neurologen, Virologen sowie Infektiologen, Anasthesisten und Allgemeinmediziner in Klinik und Praxis und dient zur Information fur andere medizinische Fachrichtungen, die an der Behandlung des Zoster beteiligt sind. Daruber hinaus soll die Leitlinie Kostentragern und politischen Entscheidungstragern zur Orientierung dienen. Die Leitlinie wurde im formellen Konsensusverfahren (S2k) von Dermatologen, Virologen/Infektiologen, Ophthalmologen, HNO-Arzten, Neurologen, Padiatern und Anasthesisten/Schmerzmedizinern erstellt. Die Leitlinie stellt einen Uberblick uber die klinische und molekulare Diagnostik sowie den Antigennachweis, die Antikorperkultur und Viruskultur dar. Diagnostisch besondere Situationen und komplizierte Verlaufe der Erkrankung finden ebenfalls Berucksichtigung. Die antivirale Therapie des Zoster und der Postzosterneuralgie wird im Allgemeinen und fur besondere Situationen dargelegt. Detaillierte Angaben zur Schmerzbehandlung finden Erwahnung und sind in einer Ubersicht dargestellt. Ebenso werden die lokaltherapeutischen Masnahmen thematisiert.

The present guidelines are aimed at residents and board-certified specialists in the fields of dermatology, ophthalmology, ENT, pediatrics, neurology, virology, infectious diseases, anesthesiology, general medicine and any other medical specialties involved in the management of patients with herpes zoster. They are also intended as a guide for policymakers and health insurance funds. The guidelines were developed by dermatologists, virologists, ophthalmologists, ENT physicians, neurologists, pediatricians and anesthesiologists/pain specialists using a formal consensus process (S2k). Readers are provided with an overview of the clinical and molecular diagnostic workup, including antigen detection, antibody tests and viral culture. Special diagnostic situations and complicated disease courses are discussed. The authors address general and special aspects of antiviral therapy for herpes zoster and postherpetic neuralgia. Furthermore, the guidelines provide detailed information on pain management including a schematic overview, and they conclude with a discussion of topical treatment options.

Sexually transmitted infections and sexually transmitted diseases such as syphilis are a great problem for public health systems worldwide. Syphilis can be curatively treated with penicillin after early diagnosis, competent therapy and consistent monitoring. The fundamentals of syphilis diagnostics are direct and serological methods for pathogen detection. Prevention of syphilis includes exposition prophylaxis and in particular the routine use of condoms and the consistent education of affected persons and their sexual contacts.

In Germany more than 3,500 people become infected with syphilis annually. As elsewhere in Western Europe there is a low level endemicity with a concentration among population subgroups with high rates of partner exchange, such as men who have sex with other men. In Germany after initially reduced numbers of cases, the incidence rate has increased after the turn of the millennium. In 2011 the incidence reached 4.5 cases per 100,000 inhabitants, which is the highest incidence since the introduction of the Infection Protection Act of 2001. Syphilis, like other sexually transmitted infections and diseases with its manifold clinical manifestations and complex diagnostics, is a large global problem for public health systems. The recent resurgence of syphilis presents a challenge for all physicians but particularly for dermatologists and venereologists because the skin and adjacent mucous membranes are initially affected. Rapid diagnosis, differential diagnosis, consequent treatment and monitoring can cure the disease. Prevention of misdiagnosis is essential otherwise severe, sometimes fatal cardiovascular complications, neurosyphilis and transfer to unborn and newborn children can occur. The synergy of syphilis and sexually transmitted human immunodeficiency virus (HIV) is of special importance. Syphilis together with genital herpes and other sexually transmitted genital and oral ulcers is an important pacemaker for HIV.

Background Nephrogenic systemic fibrosis (NSF) represents a rare fibrosing disorder occurring after administration of gadolinium-containing contrast agents during renal insufficiency. In order to prove the effect of gadolinium elimination on clinical signs, we identified and quantified gadolinium in skin biopsies of a 62-year-old patient with NSF with regard to improving skin lesions after recovery of renal function. Methods Gadolinium deposits were visualized and identified in NSF skin biopsies by light microscopy and transmission electron microscopy (EM) and by scanning EM. Inductively coupled plasma-mass spectrometry (ICPMS) was used for quantifying gadolinium concentration. Results Transmission EM studies revealed electron-dense material in connective matrix around blood vessels and inside lysosomes of histiocytes and fibroblasts. A remarkable reduction of gadolinium deposits was observed in transmission EM and scanning EM and confirmed by ICPMS in follow-up biopsies. After spontaneous recovery of renal function, his skin induration improved notably over the next 2 years. Conclusions The reduction of clinical and histomorphological signs of NSF correlated with decreasing gadolinium concentration in skin biopsies within 3 years. Our study suggests a possible pathogenetic mechanism of NSF including a chance for recovery after elimination of gadolinium and reduced histamine liberation by mast cells.

Summary Background: No consistent data are available on the currently employed diagnostic tools for autoimmune bullous diseases in Germany. The aim of this survey was to describe currently performed diagnostic methods for bullous autoimmune diseases in German dermatology departments. Methods: A standardized questionnaire evaluated the available diagnostic methods i. e. direct immunofluorescence microscopy (IFM), indirect IFM, commercial ELISA systems, and non-commercial serological tests as well as the number of samples per year in all 34 university and 39 non-university dermatology departments. Results: The overall return rate was 89 %, 100 % and 79 % for the university and non-university departments, respectively. Direct IFM was the most frequently used method and was applied in 98 % of the responding departments. In 74 % of the responding departments, indirect IFM was used mainly on monkey esophagus and human salt-split skin. Commercial ELISA systems were employed in 58 % of the clinics; all of them used anti-desmoglein ELISA, while anti-BP180 and anti-BP230 ELISA were established in 49 % and 48 % of departments, respectively. Non-commercial analytic methods were only performed in 22 % of the departments. Conclusions: The high return rate of this survey allows a relatively precise description of the current diagnostic methods used in German dermatology departments. Standard diagnostic tests are available nationwide and in bullous pemphigoid and pemphigus, the antigen-specific detection of autoantibodies is routinely performed in half of the departments. Rare disorders may be diagnosed by cooperation with some specialized centers.

Background: Although rice (Oryza sativa) is one of the most common cereals produced and consumed around the world, there have been only a few reports on immediate hypersensitivity reactions after ingestion of rice. Few clinical studies on rice allergy in Asia have been reported concerning rhinitis, asthma and atopic dermatitis. In this case study, we identify allergens presumably responsible for anaphylaxis after ingestion of rice in a German patient. Methods: Prick-to-prick tests, determination of specific IgE and the basophil activation test (BAT) were performed to confirm IgE-mediated allergy. IgE reactivity was further analyzed by immunoblotting of protein extracts from cooked commercial rice products. Rice allergens were purified, subjected to N-terminal sequencing and characterized by IgE binding and IgE inhibition assays using additional sera from 8 subjects with sensitization to rice and/or a history of hypersensitivity symptoms after rice ingestion. Results: Prick-to-prick tests were positive to raw and cooked rice (basmati rice and long-grain rice) and preparations of different rice extracts. Specific IgE against rice (f9) was 1.87 kUA/l. The BAT showed specific IgE-mediated activation of basophils after stimulation with rice extracts. Four IgE-reactive rice proteins with an apparent molecular weight of 49, 52, 56 and 98 kDa were identified. Interestingly, only binding to the 56-kDa glycoprotein was at least partially independent from cross-reactive carbohydrate determinants (CCD), whereas IgE binding to the other rice proteins was completely inhibited by pre-incubation with the CCD MUXF derived from bromelain. Conclusions: Yet unidentified high-molecular-weight allergens from rice seeds, predominantly a 56-kDa glycoprotein, seem to be responsible for anaphylaxis after consumption of rice in a German patient.

Trotz einiger hoffnungsvoller therapeutischer Entwicklungen, wie z. B. die Lokaltherapie mit einer Salbe aus Derivaten des grunen Tees, bleibt die Therapie der anogenitalen Warzen ein Problem. Sowohl arztliche Behandlungen als auch die Selbstbehandlung durch die Patienten sind nicht vollig zufriedenstellend. Die aktuellen Therapieformen mit hohen Rezidivquoten zusammen mit der zunehmenden Inzidenz und Krankheitslast sind Indikatoren dafur, dass die quadrivalente prophylaktische VLP („virus like particle“)-HPV-6-, -11-, -16-, -18-Vakzine zur Kontrolle HPV-assoziierter Neoplasien wie anogenitale Warzen vermehrt eingesetzt werden sollte.

Persistent infection with HPV 16 and 18 has been causally associated with the development of cervical cancer and its precursor lesions as well as with other carcinomas and their precursors, e.g. some vulvar and vaginal cancers. Furthermore HPV 6 and 11 are responsible for anogenital condylomata acuminata in more than 90% of cases. With the recently developed prophylactic bivalent (HPV 16 and 18) and quadrivalent (HPV 6, 11, 16 and 18) vaccines, it is possible to prevent infection of the cervical epithelium and other squamous epithelia, the development of premalignant lesions and, in the case of the quadrivalent vaccine, the development of condylomata acuminata. The following paper represents a summary of the full-text version of the German evidence-based Guidelines, including all evidence-based recommendations regarding the safety as well as the efficacy of the vaccines in preventing CIN, VIN/VaIN, genital warts and other HPV-associated lesions.

In the present report, the possible role of a recently described functional polymorphism of the osteopontin (OPN) promoter at position −443 (−443T/C) for OPN expression in melanoma cells was addressed. As shown by real-time PCR analysis, melanoma metastases that were homozygous for the −443C allele expressed significantly higher levels of OPN mRNA compared with those that were either heterozygous (−443T/C) or homozygous for the −443T allele. In line with this, immunoblotting showed significantly enhanced baseline and bFGF-induced OPN protein expression in melanoma cell lines which were homozygous for the −443C allele, compared with cell lines with other allelic variants. Similar results were obtained in in vitro luciferase assays. Chromatin immunoprecipitation (ChIP) demonstrated binding of c-Myb to the −443 OPN promoter region, and binding could significantly be enhanced after bFGF stimulation. Moreover, as shown by electrophoretic mobility shift assays (EMSA), recombinant DNA-binding domain of c-Myb bound in a sequence-specific manner to this region. Finally, the role of c-Myb for OPN gene regulation via binding to the −443 promoter region could be further substantiated by ectopic overexpression of c-Myb in melanoma cells, using different reporter gene constructs. Taken together, it is demonstrated that the −443 promoter region exerts influence on OPN gene expression in melanoma cells, and differential binding of c-Myb transcription factor appears to play a major role in this process. These findings might be a feasible explanation for different OPN expression levels in metastatic tumors and may also have prognostic and therapeutic relevance. © 2008 Wiley-Liss, Inc.

Der gegen die HPV-Typen 6, 11, 16 und 18 gerichtete prophylaktische tetravalente Impfstoff ist nicht nur hoch wirksam gegen HPV-16- und -18-assoziierte Zervixkarzinome und deren Vorstufen sowie gegen hochgradige prakanzerose Lasionen der Vulva und Vagina, sondern auch gegen HPV-6- und -11-assoziierte Genitalwarzen. Damit fallt die HPV-Impfung auch in den Verantwortungsbereich der Dermatologen. Eine Umfrage, an der sich 770 deutsche Dermatologen beteiligten, zeigt eine grose Zustimmung zur HPV-Impfung: Zwei Drittel der Befragten wird die Impfung ihren Patienten empfehlen, wenn sie diese als medizinisch sinnvoll erachten – unabhangig von einer Kostenerstattung und der STIKO-Empfehlung. Zugleich wird deutlich, dass die HPV-Impfung im Praxisalltag der Dermatologen noch nicht ausreichend etabliert ist. Vor dem Hintergrund der breiten Wirksamkeit des tetravalenten HPV-Impfstoffs sollten jedoch auch Dermatologen ihre Patienten aktiv auf die HPV-Impfung ansprechen. Grundlage und Orientierungshilfe ist die aktuelle AWMF-S3-Leitlinie zur „Impfpravention HPV-assoziierter Neoplasien“.

Persistent condylomata acuminata in a 21-year-old patient with diabetes mellitus were treated with highly purified interferon-alpha (IFN-alpha) obtained by recombinant DNA technology. Daily dose was 1.5 X 10(6) IU, given subcutaneously. Already during treatment the condylomata regressed. Two weeks after the end of therapy, i.e. after a total dose of 10.5 X 10(6) IU IFN-alpha, all condylomata had completely receded. Blood glucose levels remained constant with concomitant insulin therapy. Toxic side-effects or antibodies to IFN-alpha were not observed.

Contrast material is generally well tolerated although approximately 1% of patients who receive low-osmolar nonionic contrast material will develop anaphylaxis symptoms. Because most anaphylactic reactions are mild and nonallergic, clinically mimicking immunoglobulin E (IgE)-mediated allergy, diagnostic skin testing has been discussed controversially in the past and prophylactic pretreatment drug regimens are recommended instead. In the past 6 years, all patients with contrast material-induced anaphylaxis have been subjected to allergologic diagnostic procedures to clearly differentiate allergic and nonallergic anaphylaxis. Thus the purpose of our study was to identify and differentiate IgE-mediated allergy and nonallergic contrast material-induced hypersensitivity. Furthermore, the objective of our diagnostic procedures was not only to identify the culprit contrast material but also to find alternative contrast material for future radiologic interventions.We evaluated 96 patients with anaphylaxis symptoms after contrast material application using standardized intradermal skin testing. In patients with positive skin tests, the IgE-mediated allergy was further evaluated with in vitro and challenge tests.In four patients (suffering from anaphylaxis grades 2 and 3) out of the 96 (4.2%), skin tests and basophil activation tests strongly suggested IgE-mediated allergy to the contrast materials iopromide (two patients), iomeprol, and iopentol. In two patients with allergies to iopromide and iomeprol, alternative nonionic monomer contrast materials were tolerated, as identified in controlled challenge tests with iopamidol and iopromide, respectively.The evaluation of patients with contrast material-induced anaphylaxis (at least those with anaphylaxisor = grade 2) should always include appropriate skin tests ensuring that patients with an IgE-mediated allergy are not missed. Moreover, allergologic testing may identify a contrast material of the group of nonionic monomers that will be tolerated in future radiologic interventions.

Treatment of genital warts (condylomata acuminata) is still not completely satisfactory, despite the introduction of imiquimod 5% cream. With the development of Polyphenon E 15% ointment, progress has been made towards optimized, patient-friendly treatment of genital warts. Polyphenon E is a mixture of different polyphenols/catechins from green tea extracts (Camilla sinensis), which are known to have antioxidative, antiinflammatory, anti-proliferative and anticancer activities. In 3 placebo-controlled clinical studies safety and efficacy of Polyphenol E 15% ointment was studied in a total of 1400 patients with genital warts from Europe, North- and South America as well as South Africa. Complete responses with total healing of genital warts were seen in 54.9% of the patients in contrast to 35.4% of patients receiving placebo (p >0.001) (Combined study data). The recurrence rate was 6.2%. Polyphenon E offers special advantages with regard to its very good safety profile. Systemic adverse reactions are unlikely. Mild to moderate local reactions are of short duration. "Drug-holidays" are not necessary and the ointment does not have to be washed off. There is no contraindication for uncircumcised men with genital warts.

Die prophylaktischen HPV-L1-VLP-quadrivalenten und -bivalenten Impfstoffe sind von groser Bedeutung fur Patienten, die von Dermatologen und Venerologen betreut werden. Beide Impfstoffe schutzen vor HPV16- und HPV18-assoziierten genitoanalen Karzinomen und vor Karzinomen der Mundhohle, des oberen Respirationstrakts und extragenitalen Karzinomen der Haut v. a. im Bereich der Finger und der periungualen Region. Die quadrivalente HPV6-, -11-, -16-, -18-Vakzine schutzt auch vor genitoanalen Warzen. Hierbei handelt es sich um die haufigsten gutartigen Neoplasien des Genitale und der Perianalregion. Seit Oktober ist Gardasil® in Deutschland fur junge Madchen zwischen 9 und 16 Jahren und fur junge Frauen zwischen 16 und 26 Jahren zugelassen. Zahlreiche Experten votieren dafur, Knaben und mannliche Jugendliche in HPV-Immunisierungsprogramme mit einzuschliesen. Manner wurden direkt von einem Impfstoff profitieren, der vor der HPV-Infektion, vor genitoanalen Warzen und vor dem Peniskarzinom sowie dem Analkarzinom schutzt. Da bei immunsupprimierten organtransplantierten und bei HIV-seropositiven Patienten ausgepragte und oft chronische Krankheitsbilder resultieren und rascher bzw. haufiger maligne Tumore auftreten, ware die Einfuhrung der prophylaktischen HPV-Impfung fur diese Personen von besonders groser Bedeutung.

Received 3 December 2006; returned 26 February 2007; revised 20 March 2007; accepted 18 April 2007Objectives: Aminopenicillin-induced exanthema poses a problem in the management of infectious dis-eases. Due to theoretically possible immunological cross-reactivity, all b-lactam drugs, i.e. penicillins,penicillin derivatives and cephalosporins, are usually avoided. The available alternative antibiotics(macrolides, quinolones and glycopeptides) may be less effective, have more side effects, and theiruse increases medical costs. Moreover, their use contributes to the increasing bacterial resistance toantibiotics. The aim of the study is to demonstrate that patients with aminopenicillin-inducedexanthema may receive specific b-lactams for future antibiotic therapy.Methods: Skin testing followed by oral challenges to identify b-lactams that are tolerated by patientsdespite confirmed delayed-type non-immunoglobulin E (IgE)-mediated allergic hypersensitivity to ami-nopenicillins.Results: Sixty-nine out of 71 patients (97.2%) with non-IgE-mediated allergic hypersensitivity to amino-penicillins tolerate cephalosporins without an aminobenzyl side chain such as cefpodoxime or cefix-ime and 51 patients (71.8%) also tolerate phenoxymethyl penicillin.Conclusions: The majority of patients with non-IgE-mediated allergic hypersensitivity to aminopenicil-lins do not cross-react to certain cephalosporins or phenoxymethyl penicillin. Skin and drug challengetests can be helpful to determine individual cross-reactivity.Keywords: drug challenge, drug provocation, non-IgE-mediated allergic hypersensitivity, skin tests

Prophylactic HPV vaccination provides an opportunity to profoundly affect cervical cancer incidence worldwide. The quadrivalent HPV VLP 6, 11, 16, 18 vaccine (Gardasil®) and the bivalent HPV VLP 16, 18 vaccine (Cervarix®) are effective for prevention of HPV infection and cervical precancerous lesions. The quadrivalent vaccine is also effective for prevention of vulvar and vaginal lesions and genital warts. With the introduction of the vaccines general issues have to be raised such as optimal age for vaccination, duration of protection after vaccination, impact on cervical cancer screening, vaccination of males and feasibility of application to developing countries. The prospects of a vaccine which will protect against the most common viral sexually transmitted infection and thereby, protect against the complications of HPV infection such as cervical cancer is extremely appealing. The success of HPV vaccination as a major public health prevention opportunity, however, will entirely depend on efficient infrastructures to deliver the vaccines and on the acceptance by individuals, parents and health care providers.

Five patients with generalized slate-gray discoloration of the skin have been diagnosed histologically as argyria in the last 35 years in the Department of Dermatology and Venereology of Rostock and Halle. Light microscopically, there was visible black pigmentation in histiocytes, fibroblasts, and multinucleated giant cells of the dermis. In the transmission electron microscope (TEM), the authors observed electron-dense deposits inside lysosomes and residual bodies of phagocytes as well as outside the cells in the connective matrix. These deposits were identified by elemental analysis in TEM and electron energy loss spectroscopy (EELS) as well as scanning electron microscope (SEM) and energy dispersive x-ray analysis (EDX) containing silver and sulfur. Therefore, they seem to consist of silver sulfide. Argyria is of low medical relevance and is very rarely induced because of silver-containing drugs. Nevertheless, there are still a lot of silver products on the market, easily available over-the-counter. Therefore, argyria should not be forgotten or missed in the diagnostics of human dermis.

The overall incidence of herpes zoster in Europe is approximately 3 per 1000 people per year and more than 10 per 1000 people per year in those aged >80 years. Post herpetic neuralgia (PHN) is a common debilitating complication of herpes zoster, particularly in patients aged >50 years, in persons with severe pain or rash at presentation, and in those with significant prodromal symptoms. Antiviral drugs can effectively control acute symptoms and, if used early enough in the course of the illness, can help prevent the development of PHN and other complications. However, despite this, many patients do not receive such treatment. The economic impact of zoster and PHN is largely underestimated in Europe. Furthermore, there is considerable variation throughout Europe in the management of herpes zoster. Use of antiviral therapy including the newer potent antiviral agents such as brivudin, which requires less frequent administration than acyclovir, is improving patient outcomes in some European countries. However, in many countries, patient awareness of herpes zoster and, as a result, overall antiviral use is low. Guidelines recommending the use of antiviral agents, particularly in patients at risk of developing PHN, are available but are not widely used. More needs to be done to educate the general public and increase awareness among primary healthcare providers of the benefits of timely and appropriate pharmacological therapy in patients with herpes zoster.

Using PCR, the overall prevalence of human papillomavirus (HPV) DNA in penile carcinoma is about 40-45%, which is similar to the detection rate of HPV-DNA in vulvar carcinoma (50%). In analogy to vulvar cancer two different pathways of penile carcinogenesis seem to exist. In contrast to basaloid and warty penile cancers which are regularly HPV-associated (about 80-100%), only a part of keratinizing and verrucous penile carcinomas appear to be related with HPV (33-35%). Penile intraepithelial neoplasias comprising Bowen's disease, erythroplasia of Queyrat and bowenoid papulosis are precursor lesions of basaloid and warty carcinomas of the penis. Precursors of keratinizing carcinomas and verrucous carcinomas are not established. Whether lichen sclerosus and squamous-cell hyperplasia precede penile keratinizing carcinoma is a matter of discussion. Giant condylomata acuminata may precede the development of verrucous carcinomas in some cases. Since high risk HPVs are more frequently found in verrucous carcinomas than in giant condylomas, HPV typing may be a helpful diagnostic step to differentiate giant condyloma from verrucous carcinoma.

Hypoxia has a profound influence on progression and metastasis of malignant tumors. In the present report, we used the oligonucleotide microarray technique to identify new hypoxia-inducible genes in malignant melanoma with a special emphasis on angiogenesis factors. A commercially available Affymetrix gene chip system was used to analyze five melanoma cell lines of different aggressiveness. A total of 160 hypoxia-inducible genes were identified, clustering in four different functional clusters. In search of putative angiogenesis and tumor progression factors within these clusters, Cyr61, a recently discovered angiogenesis factor, was identified. Cyr61 was hypoxia-inducible in low aggressive melanoma cells; however, it showed constitutive high expression in highly aggressive melanoma cells. Further analyses of transcriptional mechanisms underlying Cyr61 gene expression under hypoxia demonstrated that an AP-1 binding motif within the Cyr61 promoter plays a central role in the hypoxic regulation of Cyr61. It could be shown by use of in vitro luciferase assays, electrophoretic mobility shift assays, and immunoprecipitation that hypoxia-inducible factor-1alpha interacts with c-Jun/AP-1 and may thereby contribute to Cyr61 transcriptional regulation under hypoxia. Taken together, the presented data show that Cyr61 is a hypoxia-inducible angiogenesis factor in malignant melanoma with tumor stage-dependent expression. This may argue for a hypoxia-induced selection process during tumor progression toward melanoma cells with constitutive high Cyr61 expression.

Der erfolgreiche Einsatz von Minocyclin bei der Therapie der entzundlichen Akneformen lies die Verordnungshaufigkeit in den letzten Jahren ansteigen. Damit hat sich auch das Spektrum unerwunschter Arzneimittelwirkungen erweitert. Im folgenden Beitrag berichten wir uber eine Patientin mit toxischem Leberzellschaden nach Minocyclin-Langzeittherapie, der sich im Rahmen eines Erythema exsudativum multiforme manifestierte. Die Persistenz des Ikterus mit ungewohnlicher kutaner Beteiligung in Form einer Xanthomatose wird dargestellt und ist Anlass, die Minocyclin-assoziierten Nebenwirkungen zu besprechen.

Wax moulages are valuable witnesses of the beginning of dermatology as an independent speciality. In addition, they document changes in the allocation of clinical pictures to certain conditions. This has been due to the knowledge about new etiologies of dermatologic disorders, which have been steadily increasing since the beginning of the 20th Century. Furthermore changes in the frequency of certain diseases can be recognized to some extent. The still existing moulages of the Department of Dermatology and Venereology of Rostock offer some interesting examples.

Objective The results of register studies suggest an association between Parkinson9s disease (PD) and melanoma. We studied the frequency and profile of early markers of PD in patients with malignant melanoma. Methods 100 participants were enrolled in a prospective observational study, of whom 65 had a history of high-risk cutaneous (n=53) or uveal (n=12) melanoma (31 women; age, 61.2±14.9 years) and another 35 served as control participants (19 women; 54.6±20.5 years). Participants underwent assessments of motor function (Unified PD Rating Scale; keyboard tapping test), olfactory function, colour vision, depressive symptoms, the Non-Motor Symptoms Questionnaire, and transcranial brain sonography. Raters were blinded to the diagnosis and clinical data of study participants. Results Patients with melanoma showed increased frequency of substantia nigra hyperechogenicity and prodromal motor and non-motor features of PD, especially asymmetric motor slowing and apathy. Hyposmia and colour vision disturbance were, however, infrequent. Larger echogenicity of substantia nigra correlated with lower serum iron in patients with melanoma, similar to previously reported findings in PD, and independently from the earlier findings, with lighter skin pigmentation. Substantia nigra hyperechogenicity, combined with motor asymmetry or hyposmia, was present at baseline in all participants with mild or definite parkinsonism diagnosed after 1 year. Parkinsonism was specifically related to melanoma location at the sun-exposed skin of the head or neck. Conclusions History of melanoma was associated with increased prevalence of prodromal markers of PD. Their predictive value needs to be established in long-term investigations. The similarity of serum iron characteristics found in patients with melanoma and PD deserves further research.

Human papillomavirus (HPV) infection is the most common sexually transmitted virus infection; about 40 out of 150 known HPV genotypes have been associated with genitoanal lesions in the female and male. They have been divided into low-risk (LR) and high-risk (HR) HPV types according to the association of each HPV genotype with genitoanal benign warts, genitoanal cancer and precursor lesions. For the most part, genitoanal HPV infection is equally common in men and in women. Genitoanal HPVs are predominantly transmitted by sexual intercourse. In a minor number of individuals where HR HPV infection has persisted, malignant squamous-cell tumors may develop. There are 15 mucosal oncogenic HPV types which are the etiological factor of cervical cancer and other genitoanal cancers. DNAs of HR HPV types are present in 100% of all cervical carcinomas and in 100% of the precursor lesions, the cervical intraepithelial neoplasias 2 and 3. HPV-16 and -18 alone account for 70% of the oncogenic mucosal HPV types identified. HR HPV types, mostly HPV-16 and -18, are the causes of vaginal and vulvar cancers in females, anal cancers in both genders and cancer of the penis in men. While anal cancers are linked to HR HPVs in more than 80% of cases, only 40% of vulvar cancers and 50% of penile cancers are HPV positive. Genitoanal cancers have a similar anatomy, histology and similar risk factors as well as natural histories. About 60% of vulvar and 50% of penile cancers are HPV negative, but associated with chronic inflammatory disorders, mainly lichen sclerosus. Clinical manifestations of LR HPVs in both sexes are genitoanal warts (condylomata acuminata), which are benign highly infectious tumors. The highest rate of warts is observed in females 16-24 years of age. In males the peak is at the age of 20-24 years. Diagnosis of genitoanal warts should exclude other sexually transmitted infections and diseases. A high number of genitoanal dermatoses, benign tumors, malignant squamous-cell neoplasias and cancer precursors may mimic condylomata acuminata. These malignant counterparts have to be ruled out by biopsy and a thorough histological workup. Therapy of manifest genitoanal HPV-associated lesions has profited from the development of local immunotherapy with imiquimod and local therapy with green tea derivatives (sinecatechin) 10% (Europe) and 15% (USA). Disease recurrence is a crucial problem with treatment, one that could potentially be reduced with the use of immunomodulating agents such as immuquimod and sinecatachins. Recently primary prevention of genitoanal clinical manifestations associated with HPV-6, -11, -16 and -18 including cancer precursors (intraepithelial neoplasias) has become true by the release of prophylactic quadrivalent (HPV-6, -11, -16, -18) and bivalent (HPV-16, -18) vaccines. These vaccines consist of HPV L1 virus-like particles which induce high anti-L1 serum-neutralizing antibody concentrations. Dermatologists and venereologists, general practitioners and pediatricians should cooperate with gynecologists to vaccinate young women and men in order to increase vaccination rates. In Australia and Scotland, an immense efficacy has been observed both regarding the prevention of benign genitoanal warts and cancer precursors caused by the vaccine HPV types. An absolute prerequisite of such a successful prevention against HPV-associated neoplasias is the administration of the vaccine before the first sexual contact.

Human papillomavirus (HPV) infection is the most common sexually transmitted virus infection; about 40 out of 150 known HPV genotypes have been associated with genitoanal lesions in the female and male. They have been divided into low-risk (LR) and high-risk (HR) HPV types according to the association of each HPV genotype with genitoanal benign warts, genitoanal cancer and precursor lesions. For the most part, genitoanal HPV infection is equally common in men and in women. Genitoanal HPVs are predominantly transmitted by sexual intercourse. In a minor number of individuals where HR HPV infection has persisted, malignant squamous-cell tumors may develop. There are 15 mucosal oncogenic HPV types which are the etiological factor of cervical cancer and other genitoanal cancers. DNAs of HR HPV types are present in 100% of all cervical carcinomas and in 100% of the precursor lesions, the cervical intraepithelial neoplasias 2 and 3. HPV-16 and -18 alone account for 70% of the oncogenic mucosal HPV types identified. HR HPV types, mostly HPV-16 and -18, are the causes of vaginal and vulvar cancers in females, anal cancers in both genders and cancer of the penis in men. While anal cancers are linked to HR HPVs in more than 80% of cases, only 40% of vulvar cancers and 50% of penile cancers are HPV positive. Genitoanal cancers have a similar anatomy, histology and similar risk factors as well as natural histories. About 60% of vulvar and 50% of penile cancers are HPV negative, but associated with chronic inflammatory disorders, mainly lichen sclerosus. Clinical manifestations of LR HPVs in both sexes are genitoanal warts (condylomata acuminata), which are benign highly infectious tumors. The highest rate of warts is observed in females 16-24 years of age. In males the peak is at the age of 20-24 years. Diagnosis of genitoanal warts should exclude other sexually transmitted infections and diseases. A high number of genitoanal dermatoses, benign tumors, malignant squamous-cell neoplasias and cancer precursors may mimic condylomata acuminata. These malignant counterparts have to be ruled out by biopsy and a thorough histological workup. Therapy of manifest genitoanal HPV-associated lesions has profited from the development of local immunotherapy with imiquimod and local therapy with green tea derivatives (sinecatechin) 10% (Europe) and 15% (USA). Disease recurrence is a crucial problem with treatment, one that could potentially be reduced with the use of immunomodulating agents such as immuquimod and sinecatachins. Recently primary prevention of genitoanal clinical manifestations associated with HPV-6, -11, -16 and -18 including cancer precursors (intraepithelial neoplasias) has become true by the release of prophylactic quadrivalent (HPV-6, -11, -16, -18) and bivalent (HPV-16, -18) vaccines. These vaccines consist of HPV L1 virus-like particles which induce high anti-L1 serum-neutralizing antibody concentrations. Dermatologists and venereologists, general practitioners and pediatricians should cooperate with gynecologists to vaccinate young women and men in order to increase vaccination rates. In Australia and Scotland, an immense efficacy has been observed both regarding the prevention of benign genitoanal warts and cancer precursors caused by the vaccine HPV types. An absolute prerequisite of such a successful prevention against HPV-associated neoplasias is the administration of the vaccine before the first sexual contact.

Neoplasias associated with anogenital human papilloma viruses (HPV) are characterised by high patient morbidity and mortality and by appreciable limitations in the patientʼs quality of life. Each year 530,000 women worldwide and 4800 women in Germany develop cervical cancer 1, 2. Biomolecular and epidemiological studies carried out in the past 25 years have demonstrated causal link between persisting infections with HPV 16 and HPV 18 and at least 11 other so-called high-risk HPVs (HR-HPVs) and the development of cervical cancer and its precursor lesions (so-called dysplasias or, respectively, cervical intraepithelial neoplasias – CIN). HPV 16, HPV 18 and other HR-HPVs are also the causes of other cancers and their precursors, for example, vulvar, vaginal, penile and anal cancers as well as tonsillar and throat cancers and certain forms of skin cancer. So-called low-risk HPVs (LR-HPVs) such as HPV 6 and HPV 11 are responsible for over 90 % of anogenital condylomata acuminata (anogenital warts). Condylomata acuminata are the most common viral sexually transmitted disease (STD) worldwide 3. It is estimated that around 1 % of European and German populations (aged 15–49 years) have these benign but often very unpleasant tumours. The development of a prophylactic quadrivalent vaccine (HPV 6, 11, 16, 18) and a bivalent vaccine (HPV 16, 18) has made it possible to prevent infections of the cervical epithelium and other squamous epithelia and the development of precancerous lesions. In the case of the quadrivalent vaccine (HPV 6, 11, 16, 18), the development of condylomata acuminata can also be prevented. The Standing Committee on Immunisation of the Robert Koch Institute (STIKO) has published a recommendation on HPV vaccination. Based on data from studies on the efficacy of HPV vaccines for the prevention of precancerous lesions of the cervix, vagina, and vulva, the STIKO recommends immunisation for girls aged between 12 and 17 years. The current guidelines do not contradict this recommendation but rather provide a more comprehensive supplement. The S3 guidelines focus on prophylactic vaccination against HPV-16 and HPV-18 or, respectively, HPV-6 and HPV-11 infections and thus on the prevention of cervical, vulvar, vaginal, anal and penile cancer and their precursors as well as on the primary prevention of condylomata acuminata and laryngeal papillomas. This S3 guideline thus clearly differs from other guidelines such as the S1 guideline “Condylomata acuminata and other HPV-associated clinical entities of the genitals, anus and urethra” (Guideline of the German STI Society in cooperation with the German Dermatological Society and the Paul-Ehrlich Society) and the S2 guideline of the German Society for Gynaecology and Obstetrics “Prevention, diagnostics and therapy for HPV infections and HPV-associated pre-invasive lesions in gynaecology and obstetrics”. After the debate on HPV immunisation has been concluded, the S3 guideline for the prevention of cervical cancer issued by the German Society for Gynaecology and Obstetrics will follow the recommendations in the current guideline, which will be updated. The development process and most important contents of the guideline are briefly described below. The long version of the guideline gives a more detailed account (www.awmf.org).

Cutaneous and mucocutaneous herpes simplex virus (HSV) type 1 and type 2 infections are some of the most common virus infections of man. Despite optimal laboratory diagnosis and widely improved antiviral therapy, only 20 percent of patients suffering from genital herpes are correctly diagnosed, and even less often is appropriate therapy prescribed. Atypical herpes includes vegetating forms in atypical locations, mild cases and even asymptomatic herpes. Such atypical cases often remain undetected and do not receive specific and sufficient treatment. Two case reports illustrate the importance of clinically diagnosing herpes with atypical manifestations in immunodeficient patients.

Zoster is a frequent disease of adulthood with a distinct age-dependent increase after 60. In contrast during childhood or adolescence zoster only rarely occurs. Certain risk factors such as hematologic malignancies are associated with early appearance. The typical clinical manifestation is unilateral, equally involving thoracic dermatomes. A 16-year-old patient presented with zoster in bilateral asymmetrical distribution, with trigeminal and thoracic dermatomes simultaneously affected. Despite the clinical findings and the unusual localization, there was no history, clinical nor laboratory signs of an immune suppression or any other underlying disease. Careful follow-up examinations are necessary in order to recognize systemic, especially hematologic, malignancies.

Eine Reihe unterschiedlicher Therapieformen steht heute zur Behandlung anogenitaler Warzen zur Verfugung. Im einfachsten Fall kann die Behandlung vom Patienten selbst durchgefuhrt werden. So genannte Selbsttherapiemethoden umfassen Podophyllotoxinlosung, Podophyllotoxincreme, Imiquimodcreme und die adjuvante Therapie mit Interferongel. Verfahren der Selbsttherapie sind von Therapieformen abzugrenzen, die vom Arzt eingesetzt werden. Die Wahl der Therapie hangt von der Morphologie, der Ausdehnung der Warzen und auch vom Immunstatus des Patienten ab. Die jeweilige Therapie sollte in einem Arzt-Patienten-Gesprach erortert und festgelegt werden. Unabhangig von der gewahlten Therapieform kann nach erfolgreicher Therapie HPV-DNA im umgebenen Gewebe latent persistieren und zum Wiederauftreten sichtbarer Lasionen fuhren. Wenn auch die bowenoide Papulose oft zur spontanen Abheilung neigt, kann diese intraepitheliale Neoplasie, zwar seltener als der Morbus Bowen und die Erythroplasia de Queyrat, in ein invasives Plattenepithelkarzinom ubergehen. Auch lange persistierende Warzen und Condylomata acuminata konnen entarten. Konsequente Therapie und regelmasige Nachsorge sind deshalb besonders gefordert. Ein wesentlicher Fortschritt wird in Zukunft sein, Therapieformen einzusetzen, die spezifisch gegen HPV gerichtet sind, sowohl zur Zerstorung als auch zur vollstandigen Abheilung der sichtbaren Lasionen fuhren und bleibend Rezidive verhindern. Ganz besonders wunschenswert ware die Eliminierung von HPV aus dem behandelten Gewebe.