2022 European guideline for the management of balanoposthitis.

BACKGROUND: This guideline is an update to the 2014 edition of the European guideline for the management of balanoposthitis. Balanoposthitis describes inflammation of the glans penis and prepuce and is caused by a range of disparate conditions including infection, dermatoses and premalignancy. OBJECTIVE: The main objectives of this guideline are to aid recognition of the symptoms and signs and complications of penile skin conditions and to offer recommendations on the diagnostic tests and treatment for a selected group of these conditions. METHODS: The previous guideline was updated following a literature review and priority was given to randomized controlled trial and systematic review evidence. RESULTS: The updated guideline includes amended management for infective balanitis to provide clear guidance for Group A streptococcal infections, management of on going Lichen sclerosus (to include circumcision and supportive management to reduce the recurrence of genital herpes and warts), additional regimens for Zoonoid change, use of calcineurin inhibitors in management and risk of premalignancy and change of nomenclaturefrom Premalignant conditions to Penile Intraepithelial neoplasia (PeIN). CONCLUSION: Balanoposthitis has a widerange of causes high quality evidence specific to the management of penile disease is not available for all the conditions described.

Generalized unprovoked vulvodynia; A retrospective study on the efficacy of treatment with amitriptyline, gabapentin or pregabalin.

OBJECTIVE: To describe patient characteristics of women diagnosed with generalized unprovoked vulvodynia (GUV) and to estimate efficacy and tolerability of treatment. MATERIAL AND METHODS: Retrospective observational study in 241 women who presented with GUV at three vulvar disease clinics in Rotterdam, The Netherlands during 1996-2013. Main outcome was efficacy of amitriptyline, gabapentin or pregabalin treatment. RESULTS: The median duration of symptoms was 24 months and median age 62 years (range 36-89). Most of the patients reported a burning sensation, often worsened by sitting, urinating or having intercourse. Treatment with either amitriptyline, gabapentin or pregabalin produced long lasting pain relief in 60% and temporary pain relief in 10%, while treatment was not successful in 30% of the patients. Around 30% of the patients had to stop their medication due to side effects. In 44 of the 241 (18%) women signs of vulvar dermatoses were present that could not explain the symptoms. These women experienced the same therapeutic efficacy as those without any visible abnormalities (chi-square goodness of fit p=0.49). CONCLUSIONS: Amitriptyline, gabapentin and pregabalin produced long lasting pain relief in most of the women with GUV. The 2015 International Society for the Study of Vulvovaginal Disease nomenclature acknowledges the concomitant presence of vulvar dermatoses and vulvodynia. This enables treatment of both conditions simultaneously, a situation that occurs regularly according to our study. We advocate that women with symptoms of GUV, with or without the presence of vulvar dermatoses, receive a therapeutic trial with drugs such as amitriptyline.

2017 European guidelines for the management of genital herpes.

Genital herpes is one of the commonest sexually transmitted infections worldwide. Using the best available evidence, this guideline recommends strategies for diagnosis, management, and follow-up of the condition as well as for minimising transmission. Early recognition and initiation of therapy is key and may reduce the duration of illness or avoid hospitalisation with complications, including urinary retention, meningism, or severe systemic illness. The guideline covers a range of common clinical scenarios, such as recurrent genital herpes, infection during pregnancy, and co-infection with human immunodeficiency virus.

2016 European guideline on the management of non-gonococcal urethritis.

We present the updated International Union against Sexually Transmitted Infections (IUSTI) guideline for the management of non-gonococcal urethritis in men. This guideline recommends confirmation of urethritis in symptomatic men before starting treatment. It does not recommend testing asymptomatic men for the presence of urethritis. All men with urethritis should be tested for Chlamydia trachomatis and Neisseria gonorrhoeae and ideally Mycoplasma genitalium using a nucleic acid amplification test (NAAT) as this is highly likely to improve clinical outcomes. If a NAAT is positive for gonorrhoea, a culture should be performed before treatment. In view of the increasing evidence that azithromycin 1 g may result in the development of antimicrobial resistance in M. genitalium, azithromycin 1 g is no longer recommended as first line therapy, which should be doxycycline 100 mg bd for seven days. If azithromycin is to be prescribed an extended course of 500 mg stat, then 250 mg daily for four days is to be preferred over 1 g stat. In men with persistent NGU, M. genitalium NAAT testing is recommended if not previously undertaken, as is Trichomonas vaginalis NAAT testing in populations where T. vaginalis is detectable in >2% of symptomatic women.

Evaluation of the Efficacy, Safety, and Tolerability of 3 Dose Regimens of Topical Sodium Nitrite With Citric Acid in Patients With Anogenital Warts: A Randomized Clinical Trial.

IMPORTANCE: Anogenital warts are a common disorder associated with significant physical and mental distress and a substantial cause of health care costs. OBJECTIVE: To assess the efficacy of the topical application of nitric oxide delivered using acidified nitrite. DESIGN, SETTING, AND PARTICIPANTS: A multicenter, randomized, controlled, dose-ranging clinical trial was conducted in European genitourinary medicine clinics between December 20, 2001, and January 14, 2003. Analysis was by intent to treat for all individuals initiating therapy. Participants included male and female volunteers older than 18 years with between 2 and 50 external anogenital warts. A total of 299 individuals from 40 centers were randomized to a control arm and a treatment arm that received 3 doses of acidified nitrite applied topically for 12 weeks with an additional 12 weeks of follow-up, with the final follow-up visit on January 14, 2003. INTERVENTIONS: Placebo nitrite cream and placebo citric acid cream were applied twice daily. Active treatment was divided as low dose (sodium nitrite, 3%, with citric acid, 4.5%, creams applied twice daily), middle dose (sodium nitrite, 6%, with citric acid, 9%, creams applied once daily at night, with placebo applied in the morning), and high dose (sodium nitrite, 6%, with citric acid, 9%, creams applied twice daily). MAIN OUTCOMES AND MEASURES: The primary outcome was proportion of patients with complete clinical clearance of target warts; secondary outcomes were reduction in target wart area and safety. RESULTS: Complete clinical clearance at 12 weeks occurred in 10 of 74 patients (14%; 95% CI, 6%-21%) with placebo; 11 of 72 (15%; 95% CI, 7%-24%) with low-dose treatment; 17 of 74 (23%; 95% CI, 13%-33%) with middle-dose treatment; and 22 of 70 (31%; 95% CI, 21%-42%) with high-dose treatment (P = .01). Reduction in target wart area, time to clearance, and patient and investigator assessments supported the superiority of the high-dose therapy vs placebo. There were no systemic or serious adverse events associated with treatment. However, there was a dose-related increase in itching, pain, edema, and staining of the anogenital skin associated with the active treatment. Overall, 21 patients withdrew from active treatment because of adverse events compared with none using placebo. CONCLUSIONS AND RELEVANCE: Use of sodium nitrite, 6%, with citric acid, 9%, twice daily is more effective than placebo in the treatment of anogenital warts. Treatment was associated with local irritant adverse effects. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02015260.

Neonatal herpes infections in The Netherlands in the period 2006-2011.

OBJECTIVE: To monitor the incidence of neonatal herpes in The Netherlands between 2006 and 2011, as well as the adherence to the rather conservative Dutch prevention policy. METHODS: Questionnaires were sent to all virology laboratories (n = 44), gynaecology and paediatrics departments of all hospitals in The Netherlands (n = 89). Questionnaires for the laboratories pertained to rates of proven cases of neonatal herpes; for the gynaecologists and paediatricians it pertained to rates of genital herpes during pregnancy and neonatal herpes, and their policy. For gynaecologists this concerned the risk of herpes simplex virus transmission in case of primary genital herpes during pregnancy or labour; for paediatricians it concerned the diagnostic policy in a neonate suspected of neonatal herpes. RESULTS: For the period 2006-2011 38 cases of neonatal herpes were reported, yielding an incidence of 4.7 per 100,000 births. The estimated annual number of pregnant women with primary or recurrent genital herpes was 278. Of the responding gynaecologists and paediatricians, only 59% and up to 39%, respectively, reported a policy in accordance with the national guideline. CONCLUSIONS: The incidence of neonatal herpes in The Netherlands seems to have increased in the period 2006-2011. Combined with suboptimal guideline adherence this warrants strategies to improve awareness and subsequent adherence.

[A woman with overlapping growth of nail plate fragments]. / Een vrouw met dakpansgewijze groei van de teennagels.

A 38-year-old woman presented with nail abnormalities on both of the halluces, consisting of overlapping growth of nail plate fragments, diagnosed as onychomadesis. The onychomadesis was provoked by trauma.

2013 European guideline for the management of balanoposthitis.

Balanoposthitis can be caused by a disparate range of conditions affecting the penile skin. This guideline concentrates on a selected group of conditions and offers recommendations on the diagnostic tests and treatment regimens needed for the effective management of balanoposthitis.

Self-sampling in the diagnosis of recurrent vulvovaginal candidosis.

OBJECTIVE: This study aimed to determine the accuracy and feasibility of self-sampling in patients suspected of having recurrent vulvovaginal candidosis (RVC). MATERIALS AND METHODS: Of 441 patients with symptoms suggestive of RVC presenting during an 8-year period (January 2000 to December 2007) at a dermatology clinic, 277 were instructed to perform weekly vaginal self-sampling for a period of up to 8 weeks. Demographic charactervistics, medical history, physical examination, culture results, and therapeutic efficacy were analyzed with Fisher exact, χ test, or Student t test. RESULTS: When only considering the results of the culture taken at consultation, 17.1% (20/117) of RVC cases could be confirmed. Positive cultures from self-sampling confirmed another 97 cases of RVC (82.9%). The sensitivity of a single Candida culture ranged from 18% to 53%, depending on the cutoff level of growth intensity of the yeast recovered. Specificity ranged from 97% to 100%, and the positive predictive value ranged from 92% to 100%. The number of positive cultures obtained was not associated with the duration of earlier vaginal complaints or with the efficacy of prophylactic treatment. Prophylactic treatment was equally effective in patients taking fluconazole once (8/13, 61.5%) or twice (48/74, 64.9%) a month, but treatment regimes were not randomized. CONCLUSIONS: The diagnosis of RVC can be improved dramatically by self-sampling, enabling a sooner start of adequate treatment. Multiple positive cultures were not associated with disease of longer duration or more severe disease and did not influence the response to prophylactic treatment.

An autoimmune phenotype in vulvar lichen sclerosus and lichen planus: a Th1 response and high levels of microRNA-155.

Vulvar lichen sclerosus and lichen planus are T-cell-mediated chronic skin disorders. Although autoimmunity has been suggested, the exact pathogenesis of these disorders is still unknown. Therefore, the aim of the current study was to investigate the molecular and immunological mechanisms critical to the pathogenesis of vulvar lichen sclerosus and lichen planus. By using gene expression profiling and real-time RT-PCR experiments, we demonstrated a significantly increased expression of the pro-inflammatory cytokines (IFNγ, CXCR3, CXCL9, CXCL10, CXCL11, CCR5, CCL4, and CCL5) specific for a Th1 IFNγ-induced immune response. In addition, BIC/microRNA-155 (miR-155)--a microRNA involved in regulation of the immune response--was significantly upregulated in lichen sclerosus and lichen planus (9.5- and 17.7-fold change, respectively). Immunohistochemistry showed a significant T-cell response, with pronounced dermal infiltrates of CD4(+), CD8(+), and FOXP3(+) cells. In conclusion, these data demonstrate an autoimmune phenotype in vulvar lichen sclerosus and lichen planus, characterized by increased levels of Th1-specific cytokines, a dense T-cell infiltrate, and enhanced BIC/miR-155 expression.

High prevalence of sexually transmitted infections in HIV-infected men during routine outpatient visits in the Netherlands.

BACKGROUND: In the Netherlands, no guidelines exist for routine sexually transmitted infection (STI) screening of human immunodeficiency virus (HIV)-infected men having sex with men (MSM). We assessed prevalence and factors associated with asymptomatic STI. METHODS: MSM visiting HIV outpatient clinics of academic hospitals were tested for Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), syphilis, and hepatitis B and C infection. Prevalence and risk factors were studied using logistic regression. RESULTS: In total, 659 MSM were included between 2007 and 2008. STI were found in 16.0% of patients, mostly anal CT and syphilis. One new hepatitis B and 3 new hepatitis C infections were identified. In multivariate analyses, any STI (syphilis, CT, or NG) was associated with patient's age below 40 years (odds ratio [OR]: 2.5, 95% confidence interval [CI]: 1.3-5.0), having had sex with 2 or more sexual partners (OR 2.1, 95% CI: 1.2-3.5), the use of the same sexual toys with a sexual partner (OR 2.2, 95% CI: 1.0-4.9), and enema use before sex (OR: 2.3, 95% 1.2-4.2). Syphilis was independently associated with fisting with gloves versus no fisting (OR: 4.9, 95% CI: 1.7-13.7) and with rimming (OR: 5.0, 95% CI: 1.7-15.0). CT or NG were associated with age below 45 years (age 40-44 years: OR: 2.4, 95% CI: 1.1-5.3; age <40 years: OR: 2.4, 95% CI: 1.1-5.4), enema use before sex (OR: 2.4, 95% CI: 1.3-4.4) and drug use during sex (OR: 2.4, 95% CI: 1.4-4.0). CONCLUSIONS: High-risk sexual behavior was very common, and 16% of HIV-infected MSM in HIV care had an asymptomatic STI, mostly anal CT and syphilis. Development of STI screening guidelines is recommended.

Different DNA damage and cell cycle checkpoint control in low- and high-risk human papillomavirus infections of the vulva.

Human papillomavirus (HPV) infections may result in benign hyperplasia, caused by low-risk HPV types, or (pre)malignant lesions caused by high-risk HPV types. The molecular basis of this difference in malignant potential is not completely understood. Here, we performed gene profiling of different HPV infected vulvar tissues (condylomata acuminata (n = 5), usual type vulvar intraepithelial neoplasia (uVIN) (n = 9)) and control samples (n = 14) using Affymetrix Human U133A plus 2 GeneChips. Data were analyzed using OmniViz®, Partek® and Ingenuity® Software. Results were validated by real-time RT-PCR and immunostaining. Although similarities were observed between gene expression profiles of low- and high-risk HPV infected tissues (e.g., absence of estrogen receptor in condylomata and uVIN), high-risk HPV infected tissues showed more proliferation and displayed more DNA damage than tissues infected with low-risk HPV. These observations were confirmed by differential regulation of cell cycle checkpoints and by increased expression of DNA damage-biomarkers p53 and γH2AX. Furthermore, FANCA, FANCD2, BRCA1 and RAD51, key players in the DNA damage response, were significantly upregulated (p < 0.05). In addition, we compared our results with publicly available gene expression profiles of various other HPV-induced cancers (vulva, cervix and head-and-neck). This showed p16(INK4a) was the most significant marker to detect a high-risk HPV infection, but no other markers could be found. In conclusion, this study provides insight into the molecular basis of low- and high-risk HPV infections and indicates two main pathways (cell cycle and DNA damage response) that are much stronger affected by high-risk HPV as compared to low-risk HPV.

Papular colpitis: a distinct clinical entity? Symptoms, signs, histopathological diagnosis, and treatment in a series of patients seen at the Rotterdam vulvar clinic.

OBJECTIVE: To study demographic, clinical, and histopathological data as well as treatment outcome in women with papular colpitis. MATERIALS AND METHODS: Data of women (n = 18) visiting the Rotterdam vulvar clinic and meeting the diagnostic criteria for papular colpitis were retrospectively analyzed using patient records. RESULTS: Papular colpitis is usually seen in perimenopausal women and is frequently associated with copious, nonoffensive vaginal discharge and dyspareunia. Histopathological diagnosis consistently shows dense lymphocytic infiltrates. In approximately half of the women, the vulva shows Zoon-like abnormalities. Treatment with topically applied 10% hydrocortisone acetate seemed to be moderately effective. CONCLUSIONS: Papular colpitis seems to be a distinct, relatively rare and possibly autoimmune-related condition. Treatment with 10% hydrocortisone acetate may have a dramatic effect, but recurrences are common and long-term follow-up is warranted.

A retrospective study of 95 women with a clinical diagnosis of genital lichen planus.

OBJECTIVE: The aim of this retrospective clinical study was to evaluate clinical features, histopathology, treatment regimen, and follow-up in 95 patients with genital lichen planus. MATERIALS AND METHODS: We retrospectively analyzed data of 95 women diagnosed with genital lichen planus and visiting the vulvar clinic at Erasmus MC, Rotterdam, the Netherlands. RESULTS: All patients were symptomatic, most often complaining of vulvar soreness and burning (31.6%). Of all women, 34% had persistent symptoms for more than 5 years. On physical examination, 81.1% showed sharply demarcated erythematous lesions, usually located at the vestibule, and 56.8% had oral lesions. Treatment usually consisted of potent topical corticosteroids. Seventeen women (17.9%) were referred to the gynecology department for additional surgical treatment. In two of them, a vulvar squamous cell carcinoma was detected, followed by radical surgery. CONCLUSIONS: In cases with vulvar soreness and burning, sharply demarcated erythematous vulvar lesions, and the concomitant presence of oral lesions, the diagnosis of lichen planus should be considered and treatment must be initiated accordingly, even when histopathology is discordant.

Just a penile nodule...

In this paper we present a case history of a homosexual HIV-positive male with a painless nodule on the penis. Screening for sexually transmitted diseases did not detect any infection until the node perforated spontaneously. A diagnosis of lymphogranuloma venereum was made when chlamydia trachomatis type L2 DNA was extracted from the lesion. This case illustrates that standard screening may not be sufficient for making the diagnosis of lymphogranuloma venereum.

The use of serological titres of IgA and IgG in (early) discrimination between rectal infection with non-lymphogranuloma venereum and lymphogranuloma venereum serovars of Chlamydia trachomatis.

OBJECTIVES: To investigate whether serological titres of species-specific IgA and IgG antibodies in patients with rectal chlamydial infection could discriminate between infection with serovar L2 lymphogranuloma venereum (LGV) and infection with non-LGV serovars. METHODS: A total of 39 male patients with chlamydial infection of the rectum were tested for titres of IgA and IgG antibodies within 14 days after detection of the infection and 6 and 12 months after adequate treatment. Data were collected regarding demographics, sexual orientation, HIV serostatus, history of chlamydial infection, concomitant sexually transmitted infection (STI) or HIV infection, hepatitis C virus antibodies and new STIs during follow-up. RESULTS: Between May 2003 and November 2005, 24 men with confirmed L2 proctitis and 15 men with non-LGV rectal chlamydial infection were recruited. In multivariable analyses, both high titre of IgA within 14 days after detection of the infection and older age of the individual were found significantly associated with L2 proctitis (p<0.001 and p = 0.001, respectively). A total sum score of seven times IgA titre and individual's age >or=50 years resulted in an overall sensitivity of 92% and specificity of 100%. This total sum score was highly accurate for detection of LGV proctitis, with an area under the curve in a receiver operating characteristic curve of 0.989. CONCLUSIONS: An increased IgA antibody response and the age of the infected individual are of possible diagnostic value for (early) detection of LGV proctitis.

HPV related VIN: highly proliferative and diminished responsiveness to extracellular signals.

UNLABELLED: Vulvar intraepithelial neoplasia (VIN) is a premalignant disorder caused by human papillomaviruses. Basic knowledge about the molecular pathogenesis of VIN is sparse. Therefore, we have analyzed the gene expression profile of 9 VIN samples in comparison to 10 control samples by using genome wide Affymetrix Human U133A plus2 GeneChips. Results were validated by quantitative real-time RT-PCR analysis and immunostaining of a few representative genes (TACSTD1, CCNE2, AR and ESR1). Significance analysis of microarrays (SAM) showed that 1,497 genes were differentially expressed in VIN compared to controls. By analyzing the biological processes affected by the observed differences, we found that VIN appears to be a highly proliferative disease; many cyclins (CCNA, CCNB and CCNE) and almost all prereplication complex proteins are upregulated. Thereby, VIN does not seem to depend for its proliferation on paracrine or endocrine signals. Many receptors (for example ESR1 and AR) and ligands are downregulated. Furthermore, although VIN is not an invasive disease, the inhibition of expression of a marked number of cell-cell adhesion molecules seems to indicate development towards invasion. Upon reviewing apoptosis and angiogenesis, it was observed that these processes have not become significantly disregulated in VIN. IN CONCLUSION: although VIN is still a premalignant disease, it already displays several hallmarks of cancer.

HIV incidence and HIV testing behavior in men who have sex with men: using three incidence sources, The Netherlands, 1984-2005.

BACKGROUND: In The Netherlands, the western part, including Rotterdam and Amsterdam harbors the majority of the known HIV-infected population, of whom men who have sex with men (MSM) comprise the largest transmission category. Given a general rise in sexually transmitted infections (STI) and risky sexual behavior, we examine the HIV incidence among MSM in the Netherlands with data from three different sources. METHODS: To describe the HIV epidemic among MSM we use: a prospective cohort study in Rotterdam (ROHOCO: 1998-2003, n = 265) and another in Amsterdam (ACS: 1984-2005, n = 1498]) plus an anonymous HIV surveillance study (Amsterdam STI clinic: 1991-2004, n = 3733) in which HIV-positive MSM were tested with a less-sensitive HIV assay. We evaluated calendar trends in HIV incidence, also focusing on age effects. RESULTS: Since the start of the HIV epidemic in the early 1980s, incidence has declined strongly in the ACS. In recent years, an increase was noted among older MSM attending the Amsterdam STI clinic (P = 0.0334). In both cohort studies, HIV incidence was lower and recent time-trends were not statistically significant. Among recently infected men at the STI clinic, only 40% accepted named HIV testing at their STI consultation. CONCLUSIONS: Data suggest that among MSM in the Netherlands, the HIV incidence is between one and four infections per 100 person-years. The epidemic expands among older STI clinic attendees. Prevention should be developed specifically for older men, along with a more efficient HIV testing approach such as routine HIV testing of MSM when they are screened for STI.