Chikungunya associated vulvitis: case report and literature review / Vulvite associada a Chikungunya: relato de caso e revisão de literatura

Introduction: Chikungunya virus is spreading worldwide due to migration and globalization and could be presented with systemic and with unusual symptoms. Objective: To report a case of virus-transmitted infection detected in a woman during the gynecological examination at a vulvar clinic. Case report: A 73-year-old Caucasian woman attended a vulvar clinic because of dyspareunia and vulvar burning. Ulcers were observed on labia minora and perineum. A Chikungunya was diagnosed by seroconversion in paired specimens. She was prescribed prednisolone 40 mg once a day for 10 days. After oral steroid treatment, the woman had no body rashes or lesions on her genitals. Conclusion: This study emphasized that rare signs of unusual vulvitis with ulcers could be associated with Chikungunya infection.

Introdução: O vírus Chikungunya está se espalhando pelo mundo por conta da migração e da globalização, podendo apresentar sintomas sistêmicos e incomuns. Objetivo: Relatar um caso de infecção pelo vírus detectado em uma mulher por ocasião do exame ginecológico em clínica de patologia vulvar. Relato do caso: Uma mulher caucasiana de 73 anos foi a uma clínica vulvar por causa de dispareunia e queimação vulvar. Úlceras foram observadas nos pequenos lábios e no períneo. O diagnóstico de Chikungunya foi realizado por soroconversão em espécimes pareados. Foi prescrita prednisolona 40 mg uma vez ao dia por dez dias. Após o tratamento com esteróides orais, a mulher não apresentou erupções ou lesões nos órgãos genitais. Conclusão: Este estudo enfatizou que quadros raros de vulvite com úlcera podem estar associados à infecção por Chikungunya.

Vulval herpetic adhesion: a steroid success story.

Vulval adhesion is a rare but recognized local complication following genital herpes infection. We believe this is only the second reported case of successful resolution of vulval herpetic adhesion using topical potent corticosteroid as the primary early treatment.

'HPV vulvitis' revisited: frequent and persistent detection of novel epidermodysplasia verruciformis-associated HPV genotypes.

BACKGROUND: 'Human papillomavirus (HPV) vulvitis' is a disputed entity where most studies examining for genital-mucosal (GM) HPV have been negative. METHODS: Using degenerate and type specific primers for cutaneous (CU), GM and epidermodysplasia verruciformis (EV) HPV types, the prevalence of specific HPV types was investigated in biopsy specimens from 19 women with 'HPV vulvitis', seven with asymptomatic vulvar squamous papillomatosis (ASxVSP), and controls of vulvar fibroepithelial polyps (FEP) (15), vulvar condyloma (10) and normal vulva (NV) (10). RESULTS: HPV DNA/EV HPV/GM HPV/CU HPV were detected in 84/74/47/5% of vulvitis patients, 78/71/0/28% of ASxVSP, 47/20/20/7% of FEP, 10/10%/0/0 of NV and 100/0/100/10% of condyloma. Fourteen putatively novel HPV genotypes were detected in vulvitis and ASxVSP patients, but not in controls. The two most frequent novel EV HPV, Alb-4 and DL285, were detected in 9/19 (47%) and 5/19 (26%) of vulvitis cases and were persistently identified in serial biopsies. HPV co-infection and Alb-4 infection occurred significantly more frequently in vulvitis patients, particularly those complaining of 'burning' (62/62% vs. 17/7%, p < or = 0.004). Koilocytosis was identified significantly more frequently in vulvitis compared with non-condyloma controls (81% vs. 40%, p = 0.0001), and its presence correlated with detection of HPV DNA (r = 0.3, p = 0.002). CONCLUSION: The high frequency of novel EV HPV in HPV vulvitis and correlation of clinicopathologic findings with HPV DNA suggests that HPV vulvitis may indeed exist.

Human papillomavirus in vulvar vestibulitis syndrome.

OBJECTIVE: To investigate the prevalence of human papillomavirus (HPV) in patients with vulvar vestibulitis syndrome by using a recently developed polymerase chain reaction (PCR) primer set that detects known papillomavirus types. STUDY DESIGN: We retrospectively identified 38 patients with vulvar vestibulitis who underwent therapeutic surgical excision of the vestibule. Eleven controls without vestibulitis who underwent vestibular excision for conditions unrelated to HPV infection were identified prospectively. Surgical specimens were examined for the presence of HPV DNA by PCR amplification. DNA sequencing was used to determine HPV type. RESULTS: The prevalence of HPV among patients with vestibulitis was 21% vs. 36% among controls. Group B HPV types accounted for 4 of the 10 (40%) HPV types found in patients with vestibulitis. Overall, in both patient and control samples, a spectrum of HPV types was identified, encompassing many branches of the HPV phylogenetic tree. No etiologic association was apparent. CONCLUSION: This study did not support an association of HPV with vulvar vestibulitis. The low rate of observed infection in women with and without vestibulitis and the diversity of HPV types identified suggest incidental virus carriage rather than direct cause and effect. The underlying cause of this debilitating condition remains unknown.

[Perianal Bowen's disease: a case report and review of the literature]. / Perianal Bowen's disease: a case report and review of the literature.

Perianal Bowen's disease is a uncommon, slow growing, intraepidermal squamous-cell carcinoma (carcinoma in situ) of the anal region and may be a precursor to squamous carcinoma of the anus. It is associated with cervical and vulvar intraepithelial neoplasia and have human papillomavirus as a common cause. Both sexes and all races are affected, with the highest prevalence in patients aged 20 to 45 years. The symptoms of anal Bowen's disease are unspecific and the clinical findings are uncharacteristic and include pain, itching, bleeding and a disturbing lump. Biopsy and histopathologic examination is required for diagnosis and to distinguish other perianal dermatoses; thus an anogenital warts that fail to respond to conventional therapy, or change in appearance, warrant a biopsy and, where the technique is available, DNA typing to identify the viral pathogen. Infact the etiologic agent, the human papillomavirus (HPV), has been classified by DNA techniques into at least 42 types, of which 16 and 18 are considered to carry a high risk for cancer. The intraoperative findings is a lesion at the anocutaneous line: perianal or intra-anal tumor, erosion or ulceration as well as lichenoid lesion or hyperpigmentation. The disease has a proclivity for recurrence and there are many controversies concerning treatment that effectiveness remains uncertain and range from aggressive wide local excision with skin grafting when necessary to laser vaporization (argon or CO2), radiotherapy or a new immune response modifier (Imiquimod). We report a case of a 50-years-old woman with recurrence of Bowen's disease associated with vulvar HPV infection and review the literature.

A deficiency in interferon-alpha production in women with vulvar vestibulitis.

OBJECTIVE: Previous studies have suggested that interferon-alpha may be an effective treatment for some women with vulvar vestibulitis. We evaluated whether women with this syndrome had a deficiency in endogenous and induced interferon-alpha production. STUDY DESIGN: Blood was collected in heparinized tubes from 62 women with vulvar vestibulitis and 47 control women of similar age and ethnicity. Whole blood cultures were incubated in the presence of 0.1 ng/mL lipopolysaccharide (induced) or culture medium (uninduced) for 18 to 20 hours. Aliquots were tested for interferon-alpha levels by enzyme-linked immunosorbent assay. Vestibular samples were tested for human papillomavirus by polymerase chain reaction. Aliquots were also characterized for alleles of the polymorphic gene, interleukin-1 receptor antagonist, by polymerase chain reaction. RESULTS: In uninduced cultures, interferon-gamma was present in 68.1% of control subjects as opposed to 33.9% of vulvar vestibulitis patients ( P =.0005). Similarly, after lipopolysaccharide stimulation, 70.2% of control subjects and only 48.4% of patients produced interferon-alpha ( P =.03). Among the positive samples, however, there were no differences in the interferon-alpha levels between patients and control subjects. In contrast, induction of interferon gamma in response to lipopolysaccharide was similar in control subjects (78.0%) and vulvar vestibulitis patients (82.1%). Women who have a deficiency in interferon-alpha production did not have an increased prevalence of human papillomavirus infection. There was no relation between interleukin-1 receptor antagonist genotype and interferon-alpha production. CONCLUSION: An inability to produce interferon-alpha may contribute to chronic vestibular inflammation in some women.

"Primary" versus "secondary" vulvar vestibulitis: one disease, two variants.

OBJECTIVE: Our aim was to determine whether women with primary vestibulitis-since the first episode of sexual intercourse-differ in disease characteristics and outcome of operative treatment from women with secondary vestibulitis. STUDY DESIGN: A total of 111 patients with severe vulvar vestibulitis underwent perineoplasty from 1991 to 1995. Thirty-nine (35%) of them had primary vestibulitis (ie, dyspareunia from the first attempt at sexual intercourse). They were compared with 72 (65%) who had secondary vestibulitis with regard to demographic, social, and medical variables, the presence of human papillomavirus deoxyribonucleic acid, physical and histopathologic findings in the vestibule, and surgical outcome. RESULTS: Women with primary vestibulitis were 5 years younger than those who had secondary vestibulitis (22.9 +/- 2.9 years vs 27.7 +/- 8.6 years, respectively; P <.0001) and differed in their marital status (unmarried, 84% vs 56%, respectively; P <.008), parity (nulliparous, 97% vs 67%, respectively; P <.0002), and involvement of the whole vestibule (74% vs 93%, respectively; P <.006). The 2 groups were similar in all other variables, including use of oral contraception, smoking, presence of human papillomavirus, dysuria, success of perineoplasty (average, 83%), and histopathologic findings. CONCLUSIONS: Women with primary vestibulitis were younger than women with secondary vestibulitis. Most other differences were dependent on the different ages of the 2 groups. Primary and secondary vestibulitis may therefore be two presentations of the same disease.

Telomerase activity in HPV-associated vulvar vestibulitis.

OBJECTIVE: To find a possible correlation between telomerase activity, mean telomere length and human papillomavirus (HPV) presence and type in vulvar vestibulitis. STUDY DESIGN: Twenty-two tissues excised during surgery for the treatment of severe vulvar vestibulitis and nine control tissue samples were tested for telomerase activity, mean telomere length, and HPV presence and type. RESULTS: Thirty-six percent of the tissues from vestibulitis patients were infected with HPV, mainly type 16/18, and none of the control tissue samples showed presence of HPV DNA (P < .02). Telomerase activity was detected in all tissues harboring HPV DNA, whereas only 64% of tissues without HPV DNA exhibited telomerase activity (P < .02). The mean telomere length was unchanged as compared to control samples. CONCLUSION: Telomerase activity in vestibulitis may be increased as a result of HPV infection, suggesting that HPV infection may play a role in the etiology of some cases of vulvar vestibulitis.

Human papillomaviruses and vulvar vestibulitis.

OBJECTIVE: To assess the relationship between human papillomavirus (HPV) infection and vulvar vestibulitis syndrome. METHODS: From November 1995 to December 1997, 135 women with vulvar vestibulitis were compared with 322 controls who had no evidence of vulvar vestibulitis. Human papillomavirus DNA was amplified by polymerase chain reaction and detected with liquid-capture molecular assay. RESULTS: Human papillomavirus DNA was found in 29.6% of cases and in 23.9% of controls (relative risk [RR] 1.4; 95% confidence interval [CI].8, 2.2). The prevalence of HPV tended to decrease with increasing duration of pain among cases. Thus, prevalences were 37. 5%, 29.6%, and 22.0% for pain durations of 3-6 months, 7-12 months, and 13-24 months, respectively (P =.14). Prevalence of HPV also tended to increase with pain intensity among cases, but that association was not statistically significant (P =.57). Prevalence percentages for women with low, moderate, or severe pain were 27.5%, 28.8%, and 34.4%, respectively. Prevalence of HPV was slightly higher in cases with the most severe pain (34.4%) than in controls (23.9%) (RR 1.8; 95% CI.8, 4.0). In cases with the most pain in the shortest time (3-6 months), prevalence of HPV was double that of controls (50% versus 23.9%) (RR 3.5; 95% CI 1.0, 12.7; P =.054). CONCLUSION: There was little support for the idea that HPV might be related to vulvar vestibulitis.

A repetitive DNA sequence that characterizes human papillomavirus integration site into the human genome is present in vulvar vestibulitis.

OBJECTIVE: To determine the DNA sequence of polymerase chain reaction (PCR) products obtained from surgical specimens of patients with severe vulvar vestibulitis, in order to identify and type the human papillomavirus (HPV)-DNA associated with vulvar vestibulitis. STUDY DESIGN: Fifty three women, referred for dyspareunia and diagnosed as having severe vestibulitis, underwent perineoplasty operation consisting of surgical removal of the sensitive vestibule. PCR analysis using L1 HPV primer was performed, and DNA sequencing of the samples that were found to contain HPV-DNA was undertaken, using the dideoxy chain termination method. RESULTS: Using PCR, HPV-DNA was detected in 31 of 53 tissue specimens (58%). DNA sequencing of 12 HPV-positive PCR products revealed extensive homology to human Alu consensus sequence, albeit not to any known HPV sequence. CONCLUSIONS: The presence of interspersed, repetitive-DNA sequence Alu, which is known to be the preferred site for HPV integration into human genome, in the PCR product reinforces previous observations, suggesting that HPV may have a role in the pathogenesis of vulvar vestibulitis. It further implies a possible integration of the HPV into human DNA in these cases.

Vulvar disorders in prepubertal girls. A literature review.

OBJECTIVE: To review and discuss vulvar disorders in prepubertal girls. STUDY DESIGN: Literature review. RESULTS: Bacterial and fungal vulvitis, dermatitis, inflammatory dermatoses, secondary drug reactions, viral infections and a variety of vulvar tumors can all present as primary vulvar problems in prepubertal girls. In addition, systemic diseases can present with vulvar involvement. CONCLUSION: In order to facilitate optimal care of prepubertal girls with vulvar disorders, a comprehensive review of the literature is presented.

Human papillomavirus. Subclinical and atypical manifestations.

Subclinical HPV infections, together with latent infections, are probably the most likely outcome after exposure to HPV. Subclinical infection is associated with symptoms such as burning, fissuring, and dyspareunia in some patients. Only these patients should be offered treatment. Diagnosing and treating asymptomatic HPV infection cannot be recommended until better knowledge about the infectious potential of the infection in that phase is obtained. Recently, results have been presented showing a median duration of HPV infection of only 8 months, and after 24 months, only 9% of the women studied continued to be infected. This provides the possibility to reassure patients with HPV infection that it is most likely a transient infection, and one should not worry unduly. In light of this knowledge, it seems unwise to diagnose an asymptomatic infection for which no effective treatment is available and for which the natural history and consequences remain unclear; however, if these lesions were found to have the potential to transmit HPV, the patient should be so counseled.

Severe vulvar vestibulitis. Relation to HPV infection.

OBJECTIVE: To determine whether patients with human papillomavirus (HPV)-associated vestibulitis present differently from patients with HPV-negative disease and whether the presence of HPV is a predictor of the outcome of surgical treatment by perineoplasty. STUDY DESIGN: Thirty-eight women with severe vulvar vestibulitis who underwent surgical perineoplasty were found to have HPV DNA in the vestibule by polymerase chain reaction. Thirty-six other women with severe vestibulitis had no HPV DNA in the surgical specimen. The two groups were compared with regard to demographic, social and medical variables as well as physical findings in the vestibule and response to operative treatment. RESULTS: Both groups were found to be similar in respect to age (mean 25.9 +/- 7.93 versus 25.47 +/- 5.8, respectively), parity, education, smoking habits, contraceptive use, presence of primary vestibulitis, presence of dysuria and involvement of the whole vestibule (both anterior and posterior). More unmarried than married women were infected with HPV (P < .002). There was no significant correlation between the presence of HPV and the outcome of surgical treatment (P < .6, relative risk = 0.9, 95% confidence interval = 0.5-1.5). CONCLUSION: Although HPV DNA was found in more than half of women with vestibulitis, it appears to play no role in the presentation or response to surgical therapy for vulvar vestibulitis.

Is vulvar vestibulitis an inflammatory condition? A comparison of histological findings in affected and healthy women.

Vulvar vestibulitis, as defined by Friedrich, is considered to be inflammatory, despite the fact that the normal histology of this specific area has previously not been characterized. The aim of the present study was to compare the normal histology of the vulvar vestibulum with findings in localized vulvar vestibulitis. Biopsies were taken at the area of the vestibulitis, i.e. at the openings of the Bartholin's duct. Eleven control specimens were examined histologically and compared to 24 specimens obtained from 20 patients. All samples were also tested for human papillomavirus, and they were all negative. In control specimens, as well as in specimens from patients, subepithelial inflammatory cells, sometimes aggregated into lymph follicles and/or small groups of lymphocytes were found. The conclusion is reached that the occurrence of inflammatory cells in vestibular tissue is a normal finding and cannot serve as a histological indicator of vulvar vestibulitis.

Localization of latency-associated transcripts in the uterovaginal plexus of herpes simplex virus type 1 and 2 latently infected mice.

The vagina and medulla of the adrenal gland of mice vaginally infected with herpes simplex virus (HSV) types 1 and 2 were examined in the latent stage of infection (5 to 51 weeks post-infection). RNA in situ hybridization with HSV-1 and -2 latency-associated transcript (LAT) RNA probes resulted in positively stained neuronal cell nuclei in the uterovaginal plexus, but not in the medulla of the adrenal gland. These organs were chosen because HSV antigens can be detected not only in the vaginal epithelium, but also in neurons of the uterovaginal plexus and in the medulla of the adrenal gland at the acute stage of genital infection. To our knowledge, this is the first report describing LATs in neurons of the uterovaginal plexus in the genital tract of latently HSV-infected mice.

Polymerase chain reaction search for viral etiology of vulvar vestibulitis syndrome.

OBJECTIVE: Our purpose was to assess the prevalence of infections by human papillomavirus, herpes simplex virus, and cytomegalovirus among women with severe vulvar vestibulitis. STUDY DESIGN: Eighty-six women referred for dyspareunia and diagnosed as having severe vestibulitis underwent perineoplasty, including surgical removal of the sensitive vestibule. Controls included 25 age-matched patients without dyspareunia undergoing vaginal operations for various benign causes or undergoing repair of an episiotomy. Polymerase chain reaction analysis was carried out to determine the presence of viral genes. RESULTS: The prevalence of herpes simplex virus and cytomegalovirus among the subjects tested was nil, whereas human papillomavirus was detected in 46 cases (54%). The human papillomavirus present was not of types 6, 11, 16, 18, or 33. Only one woman of the 25 asymptomatic controls (4%) had human papillomavirus deoxyribonucleic acid in the vestibule (p < 0.001). CONCLUSION: Our data provide support for the idea that vulvar vestibulitis is associated with human papillomavirus deoxyribonucleic acid in more than half of cases.