Exploring reflectance confocal microscopy as a non-invasive diagnostic tool for genital lichen sclerosus.

The diagnosis of genital lichen sclerosus (LS) is often confirmed by obtaining a skin biopsy, which can lead to unwanted complications and is uncomfortable in the sensitive genital area. Thus, there is a need of finding novel, non-invasive techniques that can rapidly and accurately diagnose LS. The present study investigated the potential for reflectance confocal microscopy (RCM) to diagnose LS compared with healthy penile skin and other common penile skin disorders in males. A total of 30 male patients, including patients with LS, nonspecific balanoposthitis, plasma cell balanitis and psoriasis, and healthy individuals were included and were subject to non-invasive RCM investigation. Prominent fiber-like structures, representing hyaline sclerosis, were observed in the RCM images for almost half of the patients. Differences between healthy penile skin and LS were confirmed by identifying the edged papillae on healthy skin and their absence or obscureness in patients with LS. Notably, RCM could detect the atypical honeycomb pattern referring to dysplasia in 1 patient with LS with penile intraepithelial neoplasia. In conclusion, the present study demonstrated that RCM can detect sclerosis in penile LS. RCM can potentially become a valuable tool for monitoring patients with LS for dysplasia providing a useful non-invasive diagnostic tool for genital disorders.

Clinical Features, Complications and Autoimmunity in Male Lichen Sclerosus.

Lichen sclerosus is a chronic inflammatory disease associated with substantial morbidity. Knowledge of the aetiology and progression of lichen sclerosus is therefore needed. In this cross-sectional study, 100 male patients diagnosed with lichen sclerosus were interviewed and examined. Since there is a possible link between lichen sclerosus and autoimmunity, blood tests were analysed for thyroid disease, antinuclear antibodies and antibodies to extracellular matrix protein 1, but autoimmunity was found to be infrequent. In 72 participants active genital lichen sclerosis was observed and complications were common; 27 patients had preputial constriction and 12 meatal engagement. In total, 13 patients needed a referral to the Department of Urology, including 1 patient with suspected penile cancer. In conclusion, despite available treatment with ultra-potent steroids and circumcision, lichen sclerosus in males is frequently complicated by phimosis and meatal stenosis. However, the disease can also go into remission, as seen in 27% of our patients.

The clinical spectrum of lichen sclerosus in male patients - a retrospective study.

Lichen sclerosus (LS) is a chronic dermatosis mainly localised to the anogenital area. The aim of this study was to investigate the clinical features of LS in adult men. A retrospective analysis of records from 771 patients diagnosed with LS was made and a questionnaire was sent to all patients. The results showed that the clinical spectrum was wide. Itch, tenderness and pain were frequently reported and more than half of the patients reported that LS had a negative impact on their sexual health. Phimosis was common and almost 1/3 of the patients were circumcised before or during the study period. Eight cases (1%) of penile squamous cell carcinoma were recorded. This emphasises the need for follow-up of male patients with LS.

Frequent detection of cytomegalovirus and Epstein-Barr virus in cervical secretions from healthy young women.

OBJECTIVE: To investigate asymptomatic shedding from the uterine cervix of five human herpes viruses: cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus (HSV) type 1 and type 2 and varicella zoster virus (VZV), in young women. DESIGN: A descriptive study. SETTING: Sahlgrenska University Hospital. POPULATION: Three hundred and five young, healthy Swedish women. METHODS: Cervical specimens were analyzed for the presence of viral DNA with a quantitative real-time PCR assay. MAIN OUTCOME MEASURES: Detection of viral DNA. RESULTS: Viral DNA was detected in 66 (21.6%) of the cervical samples. The most common findings were CMV DNA, detected in 35 (11.5%), and EBV DNA, found in 32 (10.5%) of the women. HSV-1 DNA was detected in 5 (1.7%) and HSV-2 DNA in 4 (1.4%), but VZV DNA was not found. The estimated DNA level for the detected viruses was similar with a mean DNA quantity of 2.6 log genome equivalents (Geq)/mL for CMV (range 1.7-4.3), 2.5 log Geq/mL for EBV (range 1.7-4.7), 2.4 log Geq/mL for HSV-1 (range 1.7-3.5) and 2.6 log Geq/mL for HSV-2 (range 1.7-4.1). The simultaneous presence of DNA from two or more herpes viruses was detected in eight specimens. CONCLUSIONS: Asymptomatic shedding of CMV and EBV from the uterine cervix was found in one-fifth of young women. In four of the cervical samples; two with EBV, one with CMV, one with HSV-2, high amounts of viral DNA (>4 log Geq/mL) were detected suggesting a greater risk of transmitting the virus perinatally or sexually.

Clinical and microscopic signs of cervicitis and urethritis: correlation with Chlamydia trachomatis infection in female STI patients.

Chlamydia trachomatis is among the most prevalent genital infections and is an important cause of tubal factor infertility. The majority of infected females are asymptomatic. Evidence on the reliability of signs of inflammation used to predict chlamydia in female patients is inconsistent. This study examined associations between criteria routinely used in many Scandinavian sexually transmitted infection (STI) clinics and a positive chlamydia test in a high-prevalence population. Clinical and microscopic signs of cervicitis and urethritis were recorded in 99 women attending due to chlamydia infection in a sexual partner. Mucopurulent cervical discharge, easily induced bleeding from the cervix, and more polymorpho-nuclear cells than epithelial cells in vaginal wet smear all correlated significantly with a positive Chlamydia trachomatis test (odds ratios: 3.4, 4.0 and 4.8, respectively). Increased numbers of polymorphonuclear leucocytes (>30 and ≥ 5 respectively) in stained cervical and urethral smears were not significantly correlated with chlamydia infection. Hence, routine collection of cervical and urethral smears in female STI patients is questionable.

Type-specific reactivity of anti-glycoprotein G antibodies from herpes simplex virus-infected individuals is maintained by single or dual type-specific residues.

Glycoprotein G-1 (gG-1) of herpes simplex virus type 1 (HSV-1) and gG-2 of HSV-2 are the only known HSV proteins that induce type-specific human antibody responses. Recently, it was shown that purified human anti-gG-1 and anti-gG-2 antibodies presented a type-specific reactivity to immunogenic stretches with high similarity between gG-1 and gG-2. In this study, the molecular basis for this type-specific recognition was investigated employing synthetic peptides covering the indicated regions, including substitutions of the type-specific residues. The results revealed that single or dual type-specific residues localized within regions of high similarity could induce significant structural differences, explaining the type-specific recognition of the human antibody response to the gG proteins.

CD4(+) T-cell responses to herpes simplex virus type 2 (HSV-2) glycoprotein G are type specific and differ in symptomatic and asymptomatic HSV-2-infected individuals.

T-cell recognition of the secreted and membrane-bound portions of the herpes simplex virus type 2 (HSV-2) glycoprotein G (sgG-2 and mgG-2, respectively) was compared in symptomatic and asymptomatic HSV-2-infected individuals and in HSV-2-seronegative controls and the responses with HSV-1 glycoproteins C and E (gC-1 and gE-1) were compared. CD4(+) T cells from HSV-2-infected individuals specifically recognized both sgG-2 and mgG-2, whereas HSV-1-infected and HSV-seronegative controls did not respond to these glycoproteins. The responses to gC-1 and gE-1, on the other hand, were not type specific, as blood mononuclear cells from both HSV-1- and HSV-2-infected individuals responded in vitro. There was an association between the status of the infection (symptomatic versus asymptomatic) and the CD4(+) T-cell responsiveness. Symptomatic HSV-2-seropositive individuals responded with significantly lower Th1 cytokine production to sgG-2 and mgG-2 than did asymptomatic HSV-2-infected carriers, especially within the HSV-1-negative cohort. No differences in T-cell proliferation were observed between asymptomatic and symptomatic individuals. The results have implications for studies of HSV-2-specific CD4(+) T-cell reactivity in general and for analysis of immunological differences between asymptomatic and symptomatic individuals in particular.

Dichotomy of glycoprotein g gene in herpes simplex virus type 1 isolates.

Herpes simplex virus type 1 (HSV-1) encodes 11 envelope glycoproteins, of which glycoprotein G-1 (gG-1) induces a type-specific antibody response. Variability of the gG-1 gene among wild-type strains may be a factor of importance for a reliable serodiagnosis and typing of HSV-1 isolates. Here, we used a gG-1 type-specific monoclonal antibody (MAb) to screen for mutations in the immunodominant region of this protein in 108 clinical HSV-1 isolates. Of these, 42 isolates showed no reactivity to the anti-gG-1 MAb. One hundred five strains were further examined by DNA sequencing of the middle part of the gG-1 gene, encompassing 106 amino acids including the immunodominant region and epitope of the anti-gG-1 MAb. By phylogenetic comparisons based on the sequence data, we observed two (main) genetic variants of the gG-1 gene among the clinical isolates corresponding to reactivity or nonreactivity to the anti-gG-1 MAb. Furthermore, four strains appeared to be recombinants of the two gG-1 variants. In addition, one strain displayed a gG-1-negative phenotype due to a frameshift mutation, in the form of insertion of a cytosine nucleotide. When immunoglobulin G reactivity to HSV-1 in sera from patients infected with either of the two variants was investigated, no significant differences were found between the two groups, either in a type-common enzyme-linked immunosorbent assay (ELISA) or in a type-specific gG-1 antigen-based ELISA. Despite the here-documented existence of two variants of the gG-1 gene affecting the immunodominant region of the protein, other circumstances, such as early phase of infection, might be sought for explaining the seronegativity to gG-1 commonly found in a proportion of the HSV-1-infected patients.