S1 Guideline onychomycosis.

Onychomycosis is a fungal infection of the fingernails and toenails. In Europe, tinea unguium is mainly caused by dermatophytes. The diagnostic workup comprises microscopic examination, culture and/or molecular testing (nail scrapings). Local treatment with antifungal nail polish is recommended for mild or moderate nail infections. In case of moderate to severe onychomycosis, oral treatment is recommended (in the absence of contraindications). Treatment should consist of topical and systemic agents. The aim of this update of the German S1 guideline is to simplify the selection and implementation of appropriate diagnostics and treatment. The guideline was based on current international guidelines and the results of a literature review conducted by the experts of the guideline committee. This multidisciplinary committee consisted of representatives from the German Society of Dermatology (DDG), the German-Speaking Mycological Society (DMykG), the Association of German Dermatologists (BVDD), the German Society for Hygiene and Microbiology (DGHM), the German Society of Pediatric and Adolescent Medicine (DGKJ), the Working Group for Pediatric Dermatology (APD) and the German Society for Pediatric Infectious Diseases (DGPI). The Division of Evidence-based Medicine (dEBM) provided methodological assistance. The guideline was approved by the participating medical societies following a comprehensive internal and external review.

Single-center, noninterventional clinical trial to assess the safety, efficacy, and tolerability of a dimeticone-based medical device in facilitating the removal of scales after topical application in patients with psoriasis corporis or psoriasis capitis.

INTRODUCTION: Psoriasis is a frequent inflammatory skin disease affecting ~2%-3% of the population in western countries. Scaling of the psoriatic lesions is the most impairing symptom in patients with psoriasis. In contrast to conventional keratolytic treatment concepts containing salicylic acid or urea, a dimeticone-based medical device (Loyon®) removes scales in a physical way without any pharmacological effect. OBJECTIVE: To assess the efficacy and tolerability of a dimeticone-based medical device in removal of scales in patients with psoriasis corporis/capitis under real-life conditions. METHODS: Forty patients with psoriasis capitis or corporis were included and received once-daily treatments for 7 days. Clinical assessment of the psoriasis area severity index score (psoriasis corporis) and the psoriasis scalp severity index score (psoriasis capitis) was performed and evaluated at baseline, after 3 and 7 days of treatment. Baseline scaling scores and redness scores were calculated for two target lesions of the scalp or the body on a 5-point scale each. RESULTS: For the primary efficacy variable scaling score, a statistically significant decrease was observed after treatment, with a relative reduction in scaling of 36.8% after 7 days of treatment within patients affected by psoriasis capitis. Treatment success was achieved in 76.8% of patients with psoriasis capitis, and time to treatment success was evaluated to be 4.14 days for these patients and 4.33 days for patients suffering from psoriasis corporis. CONCLUSION: In conclusion, this trial demonstrated that the dimeticone-based medical device is a safe, well-tolerated, practicable, and efficient keratolytic compound, which can be well implemented in and recommended for standard therapy of psoriasis.

Topical, Non-Medicated LOYON(®) in Facilitating the Removal of Scaling in Infants and Children with Cradle Cap: a Proof-of-Concept Pilot Study.

INTRODUCTION: Cradle cap is a very common condition in infants that presents as greasy, scaly patches on the scalp within the first weeks of life. Although usually disappearing by itself, the condition worries parents because of its appearance. When removing the scales, it is crucial to prevent spot bleedings to avoid infections. The investigational medical device LOYON(®) (Cetiol(®) CC, dimethicone) solution (G. Pohl-Boskamp GmbH & Co. KG, Hohenlockstedt, Germany) has the potential to meet these needs since it removes scales gently. It was, therefore, the aim of this proof-of-concept study to assess the efficacy and safety of topically applied, non-medicated LOYON(®) in facilitating the removal of scaling in infants and children with cradle cap without inducing spot bleedings. METHODS: This single-center, open, proof-of-concept, pilot study was conducted in 20 male or female infants/children aged 3-36 months with clinically diagnosed cradle cap. The 8-day study period included one to three applications of LOYON(®). Clinical assessment of scaling and secondary parameters was performed at baseline and after treatment. Adverse events were recorded. A questionnaire on subjective efficacy and usability was handed out to the parents. RESULTS: With a maximum of three applications of LOYON(®) applied to 20 subjects, a reduction in scaling intensity from moderate or severe to very mild or mild was achieved in 80% of the subjects. Treatment success, defined as the reduction of the scaling baseline score by at least two points, was achieved in 50% of subjects. Results of this study do not indicate any safety concern. No spot bleedings were observed. LOYON(®) was generally well tolerated and overall treatment was rated as "good" by the parents/legal guardians. CONCLUSION: This study suggests that LOYON(®) is well tolerated, safe and effective in facilitating the removal of scaling in infants and children with cradle cap. With its gentle approach and rapid effect, LOYON(®) thus represents a good alternative to home remedies for treatment of cradle cap.

Prospective, comprehensive, and effective viral monitoring in Cuban children undergoing solid organ transplantation.

PURPOSE: In Cuba, viral monitoring in the post-transplant period was not routinely performed. The aim of this research is to identify the most frequent viruses that affect transplanted Cuban children, by implementing a viral follow-up during the post-transplant period. METHODS: The study population included all Cuban pediatric patients who underwent solid organ transplantation (SOT) between November 2009 and December 2012. A total of 34 transplanted pediatric patients of kidney (n = 11) and liver (n = 23) were prospectively monitored during a 34-week period for viral DNAemia and DNAuria by simultaneous detection of cytomegalovirus (CMV), Epstein-Barr virus, herpes simplex virus type 1 and 2, varicella zoster virus, human herpesvirus 6, human adenovirus, and polyomaviruses (BKV and JCV) using quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: Viral genome of at least one virus was detected in 21 of 34 recipients, 18 patients excreted virus in urine while 12 presented DNAemia. CMV (41.2%) and BKV (35.3%) were the most frequent viruses detected during the follow-up. CMV was the virus mainly associated with clinical symptoms and DNAemia. Its excretion in urine (with cut off value of 219 copies/mL) was associated with detection in plasma (p < 0.001); furthermore, CMV viruria was predictive of CMV viremia (OR:8.4, CI:2.4-29.1, p = 0.001). There was no association between high viral load and clinical complications, due to the prompt initiation of preemptive ganciclovir. CONCLUSION: This comprehensive viral monitoring program effectively prevents the development of critical viral disease, thus urge the implementation of qRT-PCR as routine for viral monitoring of transplanted Cuban organ recipients.

Kaposi's Sarcoma and Human Herpesvirus 8 in Cuba: evidence of subtype B expansion.

OBJECTIVE: To evaluate the temporal distribution (1991-2009) and associated variation of KSHV subtypes in Cuba. METHOD: Phylogenetic characterization based on the KSHV K1 gene was performed using 90 KSHV positive samples. RESULTS: Molecular characterization confirmed the prevalence of a wide range of KSHV subtypes (A: n=48 [A5=12]; C: n=15; B: n=22; and E: n=5). In the current study, we observed a significant increase in HHV-8 subtype B after 2004 (p=0.0063). This Subtype B in Cuba was associated with: heterosexual behaviour (OR: 3.63, CI: 1,2-10,98; p=0.03), with the antecedent of acquiring HIV/KSHV in Africa (p=0.0003), with nodular stage of KS lesions (OR 4.2, CI: 1.1 to 15.7; p=0.04). CONCLUSION: Our study is the first to report KSHV Subtype B expansion in Cuba, that might be reflective of a change in human behavioural pattern.

Acute morbidity associated with scabies and other ectoparasitoses rapidly improves after treatment with ivermectin.

In resource-poor settings, scabies is associated with considerable morbidity. Which factors determine morbidity and how rapidly it recedes after specific treatment is not known. Patients with scabies were recruited in three urban slums in Fortaleza, Northeast Brazil. Diagnosis was established according to dermatoscopy, skin scraping, or adhesive film test. Severity of scabies-associated morbidity was assessed semiquantitatively. Patients and close contacts were treated with oral ivermectin (200 µg/kg, repeated after 7 days) and followed up for 2 weeks. Ninety-five patients were included in the study. Papules were the most common lesion type (98.9%). Excoriations due to scratching were observed in 43.2% and bacterial superinfection in 24.2%. Predilection sites were the arms (82.1%) and the abdomen (81.1%). At baseline, 36.3% of patients complained about intense or severe itching. Intense or severe itch decreased to 6.3% 2 weeks after treatment (p=0.02). Whereas 37.5% of the patients complained about intense or severe itch-related sleep disturbances at baseline, only 8.8% reported the symptom 2 weeks after treatment (p=0.35). At baseline, the degree of itching was correlated with the degree of sleep disturbance (ρ=0.64; p<0.001). One week after the first dose of ivermectin, the intensity of itching and of sleep disturbance decreased significantly (p<0.001). In patients living in resource-poor setting, scabies was associated with considerable morbidity. Treatment with ivermectin rapidly reconstituted health in almost all cases.

Comparison of dermoscopy, skin scraping, and the adhesive tape test for the diagnosis of scabies in a resource-poor setting.

BACKGROUND: Scabies is a parasitic skin disease endemic in resource-poor communities in low-income countries. The best ways to diagnose scabies in this setting have not been investigated. OBJECTIVE: To compare the diagnostic properties of dermoscopy, the microscopic examination of a skin scraping, and the adhesive tape test in 125 patients with a presumptive diagnosis of scabies. DESIGN: A prospective evaluator-blinded study. RESULTS: The sensitivity of dermoscopy was 0.83 (95% confidence interval [CI], 0.70-0.94) and significantly higher than the sensitivity of the adhesive tape test (0.68; 95% CI, 0.52-0.81; P < .001). The sensitivity of skin scraping was low (0.46; 95% CI, 0.31-0.62). The specificity of dermoscopy was 0.46 (95% CI, 0.34-0.58); by definition, it was 1.00 for skin scraping and the adhesive tape test. The negative predictive value was identical for dermoscopy and the adhesive tape test (0.85; 95% CI, 0.69-0.94 and 0.75-0.91, respectively) but significantly lower for skin scraping (0.77; 95% CI, 0.67-0.84; P < .001). The sensitivity of dermoscopy increased with the severity of the disease, whereas the sensitivity of the adhesive tape test did not depend on this characteristic. Limitations Because of active case finding, the duration of the infestation was short and the severity of disease was rather low in most patients. The rather short duration of the infestation might have affected the diagnostic properties of each test in different ways. CONCLUSIONS: When trained personnel are available, dermoscopy is a valid tool for diagnosing scabies in a resource-poor setting. The adhesive tape test is easy to perform and, because it has high positive and negative predictive values, the test is ideal for screening purposes. Skin scraping cannot be recommended as a diagnostic tool in this setting.

Kaposi's sarcoma-associated herpesvirus load in asymptomatic contacts of Cuban epidemic KS patients.

To evaluate the pathogenic mechanisms and transmission routes involved in KSHV infection in 22 Cuban individuals who maintained close contact with epidemic KS patients, real-time PCR was used to quantify KSHV-DNA in clinical samples of plasma, saliva and peripheral blood mononuclear cells (PBMC). KSHV-DNA was detected in 72.7% (16/22) of the contacts. The highest levels of KSHV load were detected in saliva, followed by PBMC (average log copies/100 ng DNA = 1.28 and 1.12), while significantly lower levels were detected in plasma (average log copies/ml = 0.37). Two of three intra-domiciliary and two serodiscordant sexual contacts of AIDS-KS patients were infected with KSHV. The rate of KSHV-DNA detection in saliva and PBMC samples in men who have sex with men (MSM) was significantly higher than in heterosexuals (HT) (p = 0.014). MSM were more likely to harbor KSHV-DNA in saliva when compared with HT individuals (OR 4.33; 95% CI 1.117-16.8). These results emphasize that, in Cuba, KSHV horizontal transmission through saliva may occur, although homosexual behavior may predispose an individual to KSHV acquisition. Even in the absence of disease, KSHV could cause an asymptomatic systemic infection in individuals who maintain close contact with AIDS-KS patients.

Efficacy of chemical and botanical over-the-counter pediculicides available in Brazil, and off-label treatments, against head lice ex vivo.

BACKGROUND: There is a lack of reliable data on the efficacy of over-the-counter (OTC) pediculicides in Brazil. METHODS: We performed ex vivo assays of eight marketed pediculicides: 1% permethrin (Kwell, Clean Hair, Keltrina, Nedax), 0.02% deltamethrin (Deltacid, Pediderm), and two "natural" products (Piolho e Lêndea, Pilogenio). We also tested 5% permethrin (Keltrina Plus), traditional home remedies and an ivermectin-based product used in veterinary medicine. Head lice (49-52 per group) were immersed in the compound for 3 min and washed after 20 min to simulate the typical in vivo treatment protocol. Lice were examined for activity up to 24 h using stringent criteria for survival. RESULTS: Of the permethrin containing products, highest mortality was observed with Kwell and Clean Hair (97.9 and 90.2% after 4 h). Keltrina, Nedax, Keltrina Plus, and the two deltamethrin-based products showed only a low efficacy of <60% after 4 h. With exception of pure coconut oil (80% mortality after 4 h), home remedies showed a very low efficacy, and both marketed products killed few lice. The ivermectin-based product caused a mortality of 100% after 4 h. CONCLUSIONS: Most Brazilian OTC products did not show a satisfactory efficacy against head lice. Resistance may be present. Ivermectin and coconut oil are promising compounds for topical treatment. Laboratory-based tests should be used to assess resistance patterns and to identify formulations of the active ingredient that increase the efficacy. Standardized testing should be performed before a product is licensed for head lice treatment.

Simultaneous quantification of human herpesvirus 8 DNA by real time PCR in different tissues of HIV infected cuban patients with Kaposi's sarcoma.

In Cuba, previous reports have shown an increase of epidemic KS, reaching a total of 120 cases by the end of 2007, despite the use of HAART. To evaluate and compare the role of human herpes virus 8 (HHV-8) viral loads in different compartments of AIDS-related Kaposi's sarcoma (AIDS-KS) patients real-time polymerase chain reaction (RT-PCR) was used to determine the genome copy number of HHV-8 in plasma, saliva, tissue and peripheral blood mononuclear cells (PBMC) of 49 AIDS-KS patients. Overall, 98% of AIDS-KS patients harbored detectable HHV-8. HHV-8 could be detected in 91.6% of KS tissue lesions showing the highest viral load (median log = 3.14 copies/100 ng DNA) followed by saliva and PBMC which were positive in 78%, and 69.2%; respectively. In contrast, HHV-8 was detected in only 37% of plasma samples, which also showed lower viral loads. Men who had sex with men (MSM) were more likely to have three-times higher HHV-8 genome copies in KS lesions when compared with tissues from heterosexuals individuals (OR 3; 95% CI 1.1 to 12.5). These results emphasize the systemic nature of HHV-8-infection and demonstrate the possible role of saliva in HHV-8 transmission among MSM.

Role of erythropoietin receptor expression in malignant melanoma.

Recombinant human erythropoietin (Epo) is used to prevent and treat tumor-related anemia and improve quality of life in cancer patients. Recent evidence suggested that Epo may adversely affect the survival of selected cancer patients by promoting tumor growth, inhibition of apoptosis, and induction of migration. Epo unfolds its effect on the Epo receptor (EpoR). We show--to the best of our knowledge for the first time--significantly increased EpoR expression in clinical melanoma metastases and primary melanomas in comparison with different sets of nevi by quantitative real-time reverse transcriptase-PCR, immunohistochemistry, and western blot analysis. When assessing the functionality of the EpoR-signaling pathway, recombinant human Epo led to the phosphorylation of JAK-2, signal transducers and activators of transcription 3 (STAT3), and ERK1/2 in several of the melanoma cell lines that were analyzed. Besides, Epo counteracted cisplatin-induced cell death in BLM and MV3 cells. Finally, Epo promoted cell migration of MV3 cells, whereas inhibition of the JAK/STAT and ERK1/2 pathways reduced Epo-mediated migration. In summary, we show the overexpression of functional EpoR expression in about half of the analyzed clinical melanoma metastasis specimens and show anti-apoptotic as well as pro-migratory effects of Epo, which is of importance for the treatment of anemia in advanced melanoma.

Bed bugs, leeches and hookworm larvae in the skin.

Bed bugs, leeches, and hookworm-related cutaneous larva migrans are skin infestations that are usually considered of minor importance because they produce discomfort rather than cause or transmit disease. Bed bugs have been increasing tremendously in high-income countries in recent years, causing distress to affected individuals and economic loss. Infestation by land leeches causes mainly unpleasant skin reactions, whereas infestation by aquatic leeches may be more dangerous, leading to anemia and in severe cases, to death. Cutaneous larva migrans produces an intense pruritus that can be exasperating for the patient and cause sleep disturbance. An overview is given of these three infestations with a discussion of the causative agents, transmission, clinical manifestations, diagnosis, and treatment.

Accuracy of diagnosis of pediculosis capitis: visual inspection vs wet combing.

OBJECTIVE: To determine the diagnostic accuracy of visual inspection and wet combing in pediculosis capitis (head lice infestation). Visual inspection of 5 predilection sites (temples, behind the ears, and neck) was performed first, followed by wet combing of hair moistened with conditioner. Presence of mobile stages was defined as active infestation, presence of nits alone as historic infestation. DESIGN: Observer-blinded comparison of 2 diagnostic methods. SETTING: Five primary schools in which head lice infestation was epidemic. PARTICIPANTS: A total of 304 students aged 6 to 12 years. MAIN OUTCOME MEASURES: Presence of nymph, adults, and nits; sensitivity, predictive value, and accuracy of both methods. RESULTS: Visual inspection underestimated the true prevalence of active infestation by a factor of 3.5. The sensitivity of wet combing in diagnosing active infestation was significantly higher than of visual inspection (90.5% vs 28.6%; P < .001). The accuracy of the former method was 99.3% and that of the latter method, 95%. In contrast, visual inspection had a higher sensitivity for the diagnosis of historic infestation (86.1% vs 68.4%; P < .001). CONCLUSIONS: Wet combing is a very accurate method to diagnose active head lice infestation. Visual inspection is the method of choice, if one aims to determine the frequency of carriers of eggs or nits.

The epidemiology of scabies in an impoverished community in rural Brazil: presence and severity of disease are associated with poor living conditions and illiteracy.

BACKGROUND: We sought to study the epidemiology of scabies and to identify risk factors of severe disease in an impoverished rural community in northeast Brazil. METHODS: The study was designed as a repeated cross-sectional study based on two door-to-door surveys. One survey was carried out in the rainy season, the other in the dry season. The inhabitants of the community were examined for the presence of scabies and demographic, socioeconomic, and behavioral risk factors were assessed. Risk factors were analyzed using bivariate and multivariate regression analysis. RESULTS: The overall prevalence was 9.8% with no significant variation between seasons and the incidence was estimated to be 196/1000 person-years. The highest prevalence (18.2%) was observed in children younger than 4 years. Risk factors in the bivariate analysis were young age, presence of many children in the household, illiteracy, low family income, poor housing, sharing clothes and towels, and irregular use of shower. Age younger than 15 years, illiteracy, sharing of clothes, and living in the community for more than 6 months remained significant independent risk factors in multivariate regression analysis. LIMITATIONS: We used a clinical case definition; specificity and sensitivity were not verified. Men were underrepresented in the study population. CONCLUSIONS: In this impoverished community scabies is an important health problem characterized by continuous transmission throughout the year. The parasitic skin disease is embedded in a complex web of causation characterized by poor living conditions and a low level of education.

Transcriptional regulation of ASK/Dbf4 in cutaneous melanoma is dependent on E2F1.

BACKGROUND: Melanoma is a complex genetic disease, the management of which will require an in-depth understanding of the biology underlying its initiation and progression. Recently, we have reported the differential regulation of a novel gene, namely ASK/Dbf4, in melanoma and suggested upregulation of ASK/Dbf4 as a novel molecular determinant with prognostic relevance that confers a proliferative advantage in cutaneous melanoma. As trans-acting factor binding is fundamental to understand the regulation of gene expression, this study focuses on characterization of the specific transcriptional regulation of ASK/Dbf4 in melanoma. OBJECTIVE: We investigated whether ASK/Dbf4 is a transcriptional target of the important cell cycle regulator E2F1 in melanoma. RESULTS: As evidenced by gel supershift assays on nuclear extracts from various melanoma cell lines (SK-MEL-28, MV3, M13, A375 and BLM), E2F1 bound to the ASK/Dbf4 minimal promoter (MP). In addition, cisplatin-mediated abrogation of E2F1 binding to the ASK/Dbf4 MP resulted in a transcriptional decrease in ASK/Dbf4. Further, the current study also demonstrated that ASK/Dbf4 regulation was refractory to UVB, a well-known risk factor for melanoma. CONCLUSIONS: In summary, our study not only elucidated that ASK/Dbf4, a novel cell survival gene in melanoma was transcriptionally regulated by E2F1, but also that the induction of ASK/Dbf4 was refractory to UVB exposure suggesting that its upregulation was not an early event in melanomagenesis.

Cutaneous melanoma: fishing with chips.

DNA microarray technology is a versatile platform that allows rapid genetic analysis to take place on a genome-wide scale and has revolutionized the way cancers are studied. This platform has enabled researchers to characterize mechanisms central to tumorigenesis and understand important molecular events in the multi-step tumor progression model of cutaneous melanoma and other cancers. In melanoma, multiple global gene expression profiling studies using various DNA microarray platforms and various experimental designs have been performed. Each study has been able to capture and characterize either the involvement of a novel pathway or a novel cause-effect-relationship. The use of microarrays to define subclasses, to identify differentially regulated genes within a mutational context to analyze epigenetically regulated genes has resulted in an unprecedented understanding of the biology of cutaneous melanoma that may lead to more accurate diagnosis, more comprehensive prognosis, prediction and more effective therapeutic interventions. Related DNA microarray platforms like array-comparative genomic hybridization (CGH) have also been instrumental to identify many non-random chromosomal alterations; however, studies identifying validated targets as a result of CGH are limited. Thus, there exists significant opportunity to discover novel melanoma genes and translate such discoveries into meaningful clinical endpoints. In this review, we focus on various DNA microarray-based studies performed in cutaneous melanoma and summarize our current understanding of the genetics and biology of melanoma progression derived from accumulating genomic information.

Behavioral conditioning of antihistamine effects in patients with allergic rhinitis.

BACKGROUND: Allergic symptoms can be induced by behavioral conditioning. However, the conditionability of antiallergic effects has not yet been studied. Thus, we investigated whether the effects of a histamine 1 (H(1)) receptor antagonist are inducible in patients suffering from house-dust mite allergy using a behavioral conditioning procedure. METHODS: During the association phase, 30 patients with allergic house-dust mite rhinitis received a novel-tasting drink once daily, followed by a standard dose of the H(1) receptor antagonist, desloratadine, on 5 consecutive days. After 9 days of drug washout, the evocation trial commenced: 10 patients received water together with an identically looking placebo pill (water group), 11 patients were re-exposed to the novel-tasting drink and received a placebo pill [conditioned stimulus (CS); CS group] and 9 patients received water and desloratadine (drug group). RESULTS: During the association phase, desloratadine treatment decreased the subjective total symptom scores, attenuated the effects of the skin prick test for histamine and reduced basophil activation ex vivo in all groups. During the evocation trial, the water group, in which subjects were not re-exposed to the gustatory stimulus, showed a reduction in subjective total symptom scores and skin prick test results, but no inhibition of basophil activation. In contrast, re-exposure to the novel-tasting drink decreased basophil activation, the skin prick test result and the subjective symptom score in the CS group to a degree that was similar to the effects of desloratadine in the drug group. CONCLUSIONS: These data show that behaviorally conditioned effects are not only able to relieve subjective rhinitis symptoms and allergic skin reactions, but also to induce changes in effector immune functions.