Sexually transmitted pathogens causing urethritis: A mini-review and proposal of a clinically based diagnostic and therapeutic algorithm.

The purpose of this mini-review was to provide the latest information and concepts on diagnosis and treatment of the most common sexually transmitted pathogens causing urethritis. The incidence of several sexually transmitted infections that cause urethritis is increasing, and this genitourinary syndrome is among the most common reason young men see clinical care. The authors performed a literature search including the currently valid guidelines, and an overview of the most relevant pathogens is given. Moreover, the authors developed a clinically applicable diagnostic and therapeutic algorithm, because early diagnosis and correct treatment can sometimes prevent infected individuals from significant morbidity. Future research will focus on new methods to combat pathogens that cause urethritis, including vaccination.

Lymphogranuloma venereum mimicking rectal cancer (T3 N2) and causing a rectovesical fistula.

We present the case of a 66-year-old bisexual patient suffering from painful bloody defecation, linked to rectal thickening, rectovesical fistula and enlarged lymph nodes in the mesorectal area. The patient was misdiagnosed with rectal cancer (T3 N2) on MRI but the symptoms of the patient were due to lymphogranuloma venereum. After adequate treatment with doxycycline, symptoms faded within days; a control MRI showed complete regression of all pathologic alterations.

Origin of modern syphilis and emergence of a pandemic Treponema pallidum cluster.

The abrupt onslaught of the syphilis pandemic that started in the late fifteenth century established this devastating infectious disease as one of the most feared in human history1. Surprisingly, despite the availability of effective antibiotic treatment since the mid-twentieth century, this bacterial infection, which is caused by Treponema pallidum subsp. pallidum (TPA), has been re-emerging globally in the last few decades with an estimated 10.6 million cases in 2008 (ref. 2). Although resistance to penicillin has not yet been identified, an increasing number of strains fail to respond to the second-line antibiotic azithromycin3. Little is known about the genetic patterns in current infections or the evolutionary origins of the disease due to the low quantities of treponemal DNA in clinical samples and difficulties in cultivating the pathogen4. Here, we used DNA capture and whole-genome sequencing to successfully interrogate genome-wide variation from syphilis patient specimens, combined with laboratory samples of TPA and two other subspecies. Phylogenetic comparisons based on the sequenced genomes indicate that the TPA strains examined share a common ancestor after the fifteenth century, within the early modern era. Moreover, most contemporary strains are azithromycin-resistant and are members of a globally dominant cluster, named here as SS14-Ω. The cluster diversified from a common ancestor in the mid-twentieth century subsequent to the discovery of antibiotics. Its recent phylogenetic divergence and global presence point to the emergence of a pandemic strain cluster.

Gonococcal infections in Austria: a long-term observation of prevalence and resistance profiles from 1999 to 2014.

BACKGROUND AND OBJECTIVES: The increase in minimum inhibitory concentrations (MICs) of cephalosporins for Neisseria gonorrhoeae has given rise to concerns regarding potentially untreatable gonococcal infections. The goal was to ascertain the prevalence of gonorrhea in a Viennese patient group and determine resistance patterns. Another objective was to evaluate resistance profiles and MIC values of gonococcal isolates in an Austria-wide surveillance project. PATIENTS AND METHODS: From 1999 to 2014, 350,000 individuals were tested for gonococci at the Viennese Outpatient Clinic. In addition, from 2010 to 2014, the MICs of recommended antibiotics was determined in 3,584 gonococcal isolates, initially by agar dilution and breakpoint determination, and, from 2012 onwards, by Etest®. RESULTS: During the observation period, the prevalence of gonorrhea increased eightfold, with a significantly greater number of quinolone, penicillin, and tetracycline- resistant strains. In gonococcal strains isolated from across Austria, there was an increase in cefixime and ceftriaxone MICs toward breakpoints. Twenty-one isolates showed cefixime resistance, and while there was an increase in azithromycin resistance from 0.9 % (2013) to 3.2 % (2014), no resistance to ceftriaxone was observed. CONCLUSION: Currently, there is no imminent risk of untreatable gonorrhea in Austria. However, continuing the use of gonococcal cultures as a diagnostic tool for establishing resistance profiles is essential in order to monitor trends in the development of Neisseria (N.) gonorrhoeae resistance.

Higher psychological and psychovegetative strain in adolescents with atypical pigment naevi.

An observational, exploratory, cross-sectional study was performed to assess whether the presence of atypical naevi (AN) in adolescents is associated with psychological and psychovegetative stress parameters. Fifty-one students of a secondary school in Graz, Austria, completed a defined test procedure consisting of an initial period of rest, a standardised mental stress task, another period rest and a questionnaire, the change-sensitive symptom list (ASS-SYM). Electrocardiogram and blood pressure were recorded continuously. The study population was divided in two groups: probands without AN (NAN, n = 33), and probands with at least one AN (n = 18). We found higher values for the AN group in all scales of ASS-SYM, reaching statistical significance in the dimensions "nervousness and mental tension" (p = 0.025), "psychophysiological dysregulation" (p = 0.020), burden of pain" (p = 0.023) and "general symptoms and problems" (p = 0.031). Regarding physiological parameters, the AN group showed higher vegetative strain reflected in heart rate and heart rate varibility during the periods of rest as well as a reduced baroreceptor sensitivity. On the basis of our results, the presence of AN in adolescents seems to be associated with a higher vegetative arousal. Additionally, participants with AN complained significantly more often about stress-associated general psychological symptoms and problems.

Impact of mental and physical stress on blood pressure and pulse pressure under normobaric versus hypoxic conditions.

OBJECTIVE: Hypobaric hypoxia, physical and psychosocial stress may influence key cardiovascular parameters including blood pressure (BP) and pulse pressure (PP). We investigated the effects of mild hypobaric hypoxia exposure on BP and PP reactivity to mental and physical stress and to passive elevation by cable car. METHODS: 36 healthy volunteers participated in a defined test procedure consisting of a period of rest 1, mental stress task (KLT-R), period of rest 2, combined mental (KLT-R) and physical task (bicycle ergometry) and a last period of rest both at Graz, Austria (353 m asl) and at the top station Dachstein (2700 m asl). Beat-to-beat heart rate and BP were analysed both during the test procedures at Graz and at Dachstein and during passive 1000 m elevation by cable car (from 1702 m to 2700 m). RESULTS: A significant interaction of kind of stress (mental vs. combined mental and physical) and study location (Graz vs. Dachstein) was found in the systolic BP (p = .007) and PP (p = .002) changes indicating that during the combined mental and physical stress task sBP was significantly higher under hypoxic conditions whereas sBP and PP were similar during mental stress both under normobaric normoxia (Graz) and under hypobaric hypoxia (Dachstein). During the passive ascent in cable car less trivialization (psychological coping strategy) was associated with an increase in PP (p = .004). CONCLUSION: Our data show that combined mental and physical stress causes a significant higher raise in sBP and PP under hypoxic conditions whereas isolated mental stress did not affect sBP and PP under hypoxic conditions. PP-reaction to ascent in healthy subjects is not uniform. BP reactions to ascent that represents an accumulation of physical (mild hypobaric hypoxia) and psychological stressors depend on predetermined psychological traits (stress coping strategies). Thus divergent cardiovascular reactions can be explained by applying the multidimensional aspects of the biopsychosocial concept.

Heat-triggered reticular telangiectatic erythema induced by a spinal cord stimulator.

In recent years, cutaneous complications have been reported after implantation of medical devices as a result of their widespread use. We report a case of reticular telangiectatic erythema (RTE) after replacement of a spinal cord stimulator. To date, the pathogenesis of RTE has been poorly understood. Some reports have suggested that heat is involved, whereas others seem to contradict this observation. In our thermographic study, we found that heat can cause RTE.

Differentiation between balanitis and carcinoma in situ using reflectance confocal microscopy.

IMPORTANCE: Zoon plasma cell balanitis is a benign inflammatory disease of genital skin. It may be difficult to clinically distinguish between balanitis and carcinoma in situ (CIS); thus, a biopsy may be needed to exclude malignant disease. Reflectance confocal microscopy (RCM) is an in vivo imaging method to get morphologic information about architecture and single cells in the skin. OBJECTIVE: To evaluate the ability of RCM to differentiate between balanitis and CIS compared with the gold standard histopathologic methods. DESIGN: Observer blinded study. SETTING: A referral center. PARTICIPANTS: Fifteen patients with balanitis or CIS. INTERVENTION: Patients were assessed by clinical, histologic, and RCM findings. All lesions were imaged with the Vivascope 1500. In 5 cases of balanitis, the surrounding, noninvolved skin also was evaluated. MAIN OUTCOME MEASURES: Local recurrence, nodal metastasis, disease-specific death, overall death. RESULTS: The clinical diagnoses showed 9 cases of balanitis and 6 cases of CIS. With histopathologic analysis, 12 cases of balanitis and cases of CIS were diagnosed, and RCM evaluation confirmed these diagnoses. The most relevant RCM criteria for CIS were atypical honeycomb pattern, disarranged epidermal pattern, and round nucleated cells. Balanitis showed a nucleated honeycomb pattern and vermicular vessels. Scattered small bright cells and round vessels were present in all lesions. The adjacent normal skin showed a typical honeycomb pattern and round papillary vessels. CONCLUSIONS AND RELEVANCE: We were able to differentiate between balanitis and CIS. Reflectance confocal microscopy may help to avoid biopsies at this sensitive site.

Coping strategies in melanoma patients.

An observational, questionnaire-based, cross-sectional study was performed to assess whether differences in coping behaviour (positive and negative strategies) between patients with either a recent diagnosis of malignant melanoma (MM) or with benign dermatological disease, were predictive of the diagnosis. Coping strategies were assessed with the German version of the stress-coping questionnaire (SVF 120) in 46 inpatients for whom surgery was planned at the Department of Dermatology, Medical University of Graz, Austria. Subjects were divided into two groups: patients with non-metastatic MM, and patients with benign dermatological diseases (controls). The risk for the diagnosis "melanoma" decreased with higher values of "situation control" (p = 0.007) and increased with higher values of resignation (p = 0.035) and trivialisation (p = 0.039). More-over, the risk for having a MM with thickness > 1 mm decreased in patients with higher values in positive coping strategies (p < 0.34). These results suggest differences in coping behaviour between patients with MM and those with benign skin diseases and, amidst patients with MM, between patients with different MM thickness; the results may hence lead to earlier, more specific and more effective psychological interventions to improve coping in patients with MM, as differences in coping behaviour seem to appear even in the non-metastatic stage of the disease.

Imiquimod and lymphatic field clearance: a new hypothesis based on a remote immune action on skin cancer.

Basal cell carcinoma and actinic keratosis are frequent neoplasms. Topical treatments include the recently approved imiquimod cream. We describe here the case of a 68-year-old man with multiple actinic keratosis on the forehead, upper trunk and on the left cheek. In addition, an exulcerated basal cell carcinoma was observed. The patient was advised only to treat lesions on the forehead with imiquimod cream. This resulted in complete clearance of actinic keratosis within 6 weeks. At follow-up, a planned surgical excision of the basal cell carcinoma and actinic keratosis on the cheek was carried out. Histopathologically, both excision specimens no longer showed features of basal cell carcinoma or actinic keratosis, despite the fact that the imiquimod treatment was not applied to the cheek. Imiquimod cream is a topical immune response modifier, which has shown antiviral and anti-tumorous properties by inducing the production of cytokines as well as by stimulating dendritic cells and lymphocytes. Our observation supports the concept of lymphatic transport of immune cells and factors with subsequent immunological curing of tumours, not only in the treated area, but also those in the area between the imiquimod application site and the regional lymph nodes (the "lymphatic field clearance").

Histamine intolerance: lack of reproducibility of single symptoms by oral provocation with histamine: a randomised, double-blind, placebo-controlled cross-over study.

OBJECTIVES: The term histamine intolerance stands for a range of symptoms involving various effector organs after the consumption of histamine-rich food. Our intention was to objectify and quantify histamine-associated symptoms and to analyse whether oral administration of the histamine-degrading enzyme diamine oxidase (DAO) caused a reduction of symptoms. PATIENTS AND METHODS: Four Austrian centres participated. Patients suspected to be histamine intolerant were recruited. The first step consisted in the open oral provocation of these patients with 75 mg of liquid histamine. Patients who developed symptoms were tested in a randomised double blind crossover provocation protocol using histamine-containing and histamine-free tea in combination with DAO capsules or placebo. Main and secondary symptoms (strongest and weaker symptoms based on a ten-point scale) were defined, the grand total of all symptoms of the individual provocation steps was determined and changes in symptoms after administration of DAO were measured. RESULTS: Thirty nine patients reacted to the open histamine provocation and were enrolled in the blinded part. Here, both the main and secondary symptoms were not reproducible. Subjects reacted sometimes unexpectedly and randomly. Regarding the total symptom scores, the differences between the three treatment groups were statistically significant. The intake of DAO demonstrated a statistically significant reduction of histamine-associated symptoms compared to placebo (P = 0.014). CONCLUSIONS: Oral provocation with 75 mg of liquid histamine failed to reproduce histamine-associated single symptoms in many patients. One may suggest that histamine-intolerant subjects reacted with different organs on different occasions. As a consequence, reproducibility of single symptoms alone may not be appropriate to diagnose histamine-intolerance whereas a global symptom score could be more appropriate. The fact, that the intake of DAO capsules compared to placebo led to a statistically significant reduction of total symptom scores, may indirectly point in the same direction.

Efficacy and safety of imiquimod versus podophyllotoxin in the treatment of anogenital warts.

BACKGROUND: Anogenital warts are a common sexually transmitted disease caused by human papillomaviruses. Despite the fact, that imiquimod and podophyllotoxin represent common topical agents, direct comparative studies lack. This work compares the effectiveness and safety of self-applied imiquimod 5% cream and podophyllotoxin 0.5% solution. METHODS: Within 2 years, consecutive patients presenting with untreated anogenital warts were included in a randomized, open label trial. The primary endpoint was complete clearance at the end of treatment (4 weeks after the start with podophyllotoxin, 16 weeks after the start of imiquimod therapy). Side effects were evaluated as a secondary endpoint. RESULTS: A total of 45 patients, 7 women and 35 men, of whom 5 were circumcised, concluded the treatment and were eligible for evaluation. The rates of clearance of baseline warts among treatment groups were 72% (95% confidence interval [CI], 52%-86%) in the podophyllotoxin group and 75% (95% CI, 53%-98%) in the imiquimod group. Statistically, clearance rates were identical (P=1). The differences in side effects between treatment groups were statistically not significant (P=0.24). CONCLUSIONS: The current study, a direct comparison of both, confirms the previously obtained mathematical data, that imiquimod 5% cream and podophyllotoxin 0.5% solution have an identical beneficial effect on anogenital warts and are associated with identical and acceptable side effects. Both substances constitute effective and safe treatments of untreated anogenital warts in immunocompetent individuals.

Recurrent herpes simplex infection in multiple locations in an otherwise healthy boy.

An 8-year-old boy developed vesicular lesions on the skin in different parts of the body, occurring four to six times a year. He had a history of eczema herpeticum as a young child. We confirmed a diagnosis of multifocal herpes simplex infection, and hypothesize that this was a result of his previous eczema herpeticum, an unusual complication, in an otherwise healthy and immunocompetent child.