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Case–Control Study of Vulvar Vestibulitis Risk Associated with Genital Infections

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Case–Control Study of Vulvar Vestibulitis Risk Associated with Genital Infections Infect Dis Obstet Gynecol 2002;10:193–202 Case–control study of vulvar vestibulitis risk associated with genital infections Elaine M. Smith 1,2, Justine M. Ritchie 3, Rudolph Galask 2, Erica E. Pugh 1, Jian Jia3 and Joan Ricks-McGillan 1 1Department of Epidemiology, College of Public Health, 2Department of Obstetrics/Gynecology, College of Medicine and 3Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, IA Objective: Toevaluate the riskof vulvarvestibulitis syndrome (VVS) associated with genital infectionsin a case–control study. Methods: Diagnosedcases with VVS( n = 69) andage-frequency-matched healthy controls( n = 65) were enrolledfrom gynecologyclinics ina universitymedical hospital during1999. They werecompared forpotential risk factors and symptoms of disease. Results: VVScases had asignificantlyhigher riskof physician-reportedbacterial vaginosis(BV) (oddsratio, OR = 9.4), Candida albicans (OR = 5.7), pelvic inflammatory disease(PID) (OR = 11.2), trichomoniasis (OR = 20.6), andvulvar dysplasia (OR = l5.7) butno risk associated with human papillomavirus (HPV),ASCUS, cervical dysplasia,genital warts,chlamydia, genital herpesor gonorrhea. Genital symptomsreported significantly more oftenwith VVSincluded vulvar burning (91 vs.12%), dyspareunia(81 vs.15%), vulvaritching (68 vs.23%) and dysuria (54 vs. 19%) ( p < 0.0001). Conclusion: Ahistoryof genital infectionsis associated with anincreased risk of VVS.Long-term follow-up case–control studies are needed to elucidate etiologic mechanisms, methods forprevention and effective treatment. Key words:V ULVAR VESTIBULITIS ; GENITAL INFECTIONS; RISK FACTORS; VESTIBULITIS SYMPTOMS Theprevalence ofvulvar vestibulitis syndrome membrane andits underlyingappendages, the (VVS) has beenestimated toaffect approximately vestibular ductsand glands. Vestibular painmay 15%of theadultfemale populationwho are seen in developgradually or suddenly, followed by gynecologicpractices 1,2.Thecondition has been pain-free periods 1,4. definedby theInternational Society for the Study Characterizedas themost frequentcause ofdys- ofVulvar Disease (ISSVD) accordingto the pareunia,VVS is under-diagnosed,multi-factorial followingcriteria: (1) severe painon vestibular andcomplex. Patients presentwith unexplained touchor vaginal entry;(2) tenderness onpressure pain,burning, stinging and rawness localizedto the localizedwithin the vulvar vestibule; and(3) physi- vulvar area1,5.Vestibulitis patients oftenare cal findingsof erythema confinedto the vesti - misdiagnosed witha psychologicalcondition bule2,3.VVS is aninflammatory process ofthe ratherthan physically based disease 1. Previous vestibule ofthe vagina thatinvolves themucous studies have providedinconclusive evidence into Correspondenceto: Elaine M.Smith, MPH, PhD, Departmentsof Epidemiology and Biostatistics, Collegeof Public Health, University of Iowa, Iowa City, IA 52242. Email: [email protected] Clinical study 193 VVS risk and infections Smith et al. theetiology of VVS. Some studies proposethat otherphysicians in the obstetrics/ gynecology genital infectionssuch as chroniccandidiasis, her- departmentserved as resources forrecruiting pes simplex virus (HSV), humanpapillomavirus controlsubjects who were seeking routine (HPV), contactdermatitis, irritants orvulvar gynecologiccare. Thecontrols were matchedto trauma cause VVS, butthe findings have been cases basedon age-frequencyat 2-year intervals. At contradictory 6–12.Ithas beenpostulated that thetime ofenrollment, controlswere diagnosedas specific microfloramay induceinjury to thevesti- beingfree ofVVS andhaving no priorhistory of bularnerve endingsthat leads totheextreme pain thecondition. Patients signedan informedconsent as well as alterations inthe immune system 13,14. form(approved by the Human SubjectsReview Several studies also have suggested thatthere is a Boardthat oversees medical research at theuniver- hormonalcomponent that increases therisk of sity) priorto enrollingin the studyand completing developingthe syndrome possibly by altering thequestionnaire. One case andone control thequality or quantityof mucus secretions inthe declinedparticipation in the study; thus the final vestibular glands, reducingthe protective effect of sample size included69 VVS cases and65 controls. thevestibule 10.Thepurpose of this epidemiologic studywas toevaluate therole ofpathologicvaginal Procedures microbial andviral agents asrisk factorsfor VVS amongwomen diagnosed in a vulvar disease clinic Withthe exceptionof Papsmears andHPV DNA anda groupof healthywomen without this diag- testing, thediagnoses ofgenital infectionsand nosis at a university hospital tertiary care center. related diseases were thosefrom the referring physicianand a review ofthe medical chartamong thosewho were patients oftheuniversity hospital. METHODS HPV testing was performedat thetime oftheir clinicand enrollment into the study. Patients Population underwentone additional swab to test forHPV Patients withVVS were recruitedfrom the Vulvar DNAduring their routinegynecological exam. Disease Clinic at theUniversity ofIowa Hospitals TheHPV specimen was collectedimmediately andClinics (UIHC). Theclinic sees inexcess of followingthe Pap smear usinga cottontip 2500patients withvulvar andvaginal complaints applicator.Cells fromthe vulvar andvaginal region eachyear. Cases were recruitedduring two were placedin a sterile tubeof saline, centrifuged time-periods betweenAugust and September and andfrozen at -70°Cforstorage untilthe laboratory Octoberand November 1999. Patients were diag- assessment was conducted.The HPV DNA nosedas havingVVS if theyhad the ISSVD criteria specimens were evaluated byPCR amplification as describedabove. Sincenot all ofthe patients followedby DNA sequencing in the HPV labs were newlydiagnosed with the disease, theydid wherethese tests are performedroutinely using notall currentlyhave all these criteria at thetime of standardizedtechniques for other research interview. Onewoman was excludedbecause she protocols15. didnot complete the questionnaire, providing a sample size of69 cases (98.6% participation). Questionnaire and genital infection reports Between December 1999and May 2000, acontrol groupof womenwho hadnever hada diagnosis or Patients completeda 10-minute self-administered anysymptoms ofVVS were solicited fromgeneral risk-factorquestionnaire at thetime ofenrollment gynecologyclinics inthe UIHC ( n = 65) where inthe study. The research staff reviewed the theywere having annualexams. Theywere com- questionnaireand queried unanswered questions. paredwith the VVS cases forrisk-factor history Informationfocused on sociodemographiccharac- (98.5% participation).A single physicianwho has teristics, sexual behaviorand pregnancy history, diagnosedand treated thecondition for approxi- steroidhormone use (oral contraceptives(OCs) mately 20years at theUniversity ofIowa clinics andother sex steroid hormones), gynecological diagnosedall cases (RudolphGalask). He andtwo history,alcohol and smoking exposure, history of 194 INFECTIOUSDISEASES IN OBSTETRICS AND GYNECOLOGY VVS risk and infections Smith et al. genital infectionand symptoms related toVVS and youngeron average thanwere controls.There was its treatment. Responses were validated using nostatistically significant differencein income or thepatients’ medical records.Cases andcontrols educationallevels betweencases andcontrols completedthe same questionnaireexcept controls althoughdiagnosis ofVVS was more likely to omittedsections related tosome ofthe VVS occurwith increasing income(Table 1). Com- symptoms. Theresearch personnelcompleted a paredwith married women,other marital status gynecologicalhistory from which they elicited groupswere actuallyat lowerrisk ofVVS. There informationto verify adiagnosis anddate of VVS, was noassociation betweensmoking or alcohol gynecologictreatment forthe disease, irritants of andrisk ofdisease. Allof the cases and92% of VVS andother gynecological history to substan- thecontrols were non-Hispanicwhite (data not tiate patientstatements aboutsteroid hormone shown). use, sexual history,disease symptoms, genital infections,history of genital warts, abnormalPap Sexual behavior/hormone use smears, genital dysplasia andinvasive cancer,and othergenital conditionsor diseases. Thebasis for Mostpatients were heterosexual (97% cases vs. reportingvulvar intraepithelial neoplasia (VIN) 92%controls) with a fewbisexual (3 vs. 4%) or was fromthe university pathologyreport and that homosexual(0 vs. 4%). Amongcases, 6.1%( n = 4) ofthe gynecologist pathologist at thehospital. stated thatthey never hadsexual intercourse Candidiasis was evaluated separately fromreports comparedto 4% ( n =1) ofcontrols. Few VVS ofyeast infectionusing the medical recordsince women(12%) hadchanged sexual partnerssince this specific infectionhas beenthe focus of several theonset of their symptoms. Themajority of studies of VVS. partnersreported no symptoms suchas itching, irritation, burningor other indication of an infectiousagent. Themean age at first intercourse Data analysis was similar betweencases andcontrols (Table 2). Comparisons betweencases andcontrols for Age-adjustedrisks indicatethat older age at first ontinuousvariables were examined usingthe intercourseincreased therisk ofVVS more than Wilcoxonrank sum test. Significanceof risk factors twofold.Nulliparity also was associated witha after adjustingfor age was basedon the Wald significantincreased risk whereas use ofOCs statistics fromthe unconditionallogistic regression showeda
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