Vulvovaginal Candidiasis as a
Chronic Disease: Diagnostic
Criteria and Definition
Esther Hong, BSc, MBBS,1
Shreya Dixit, B...
criterion would limit our ability to identify and correctly
treat this condition.
Vulvovaginal candidiasis (VVC) is define...
determine their accuracy. All patients identified using the
criteria were fully responsive to oral antifungal therapy.
CVV...
swelling were 5 times more likely to be found in the
CVVC group compared to controls.
Vulvovaginal itch was not a signific...
A selected multivariable logistic regression analysis of
8 significant features for the identification of CVVC
demonstrate...
[8]. Our own experience with Candida polymerase chain
reaction reflects this, and we have not found it to be
positive unle...
a sensitive marker useful in the diagnosis of CVVC in this
study (p 9 .05) [16]. Patients complaining of vaginal itch
in t...
13. Fischer G, Bradford J. Vulvovaginal candidiasis in
postmenopausal women: the role of hormone replacement
therapy. J Lo...
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  1. 1. Vulvovaginal Candidiasis as a Chronic Disease: Diagnostic Criteria and Definition Esther Hong, BSc, MBBS,1 Shreya Dixit, B Med Sci, MBBS(Hons),2 Paul L. Fidel, PhD,3 Jennifer Bradford, MBBS, FRANZCOG,4 and Gayle Fischer, MBBS(Hons), FACD1 1 Northern Clinical School, University of Sydney; 2 Department of Dermatology, Royal North Shore Hospital, St Leonards, NSW, Australia; 3 Louisiana State University Health Sciences Center School of Dentistry, New Orleans, LA; and 4 University of Western Sydney, NSW, Australia h Abstract Objective. Although recurrent vulvovaginal candidiasis is defined as 4 or more discrete attacks of vulvovaginal candidiasis per year, there is no diagnostic nomenclature or definition for the many women who are chronically symp- tomatic. This study aims to establish and propose a defini- tion and a set of diagnostic criteria, which would enable clinicians to promptly identify and treat women with chronic vulvovaginal candidiasis (CVVC). Design. Prospective cohort study. Setting. Public and private vulvar dermatology out- patient clinics in Sydney, Australia. Participants. Data were obtained prospectively from 50 women with presumptive CVVC and 42 controls. Historical and clinical features of CVVC identified by expert consensus were compared between the 2 groups. Diagnostic criteria were then prospectively applied to a further 163 patients to verify their accuracy. Outcome Measures. Signs and symptoms diagnostic of CVVC. Results. The following characteristics were found to be significantly more common in women with CVVC compared to controls (p e .001): a history of positive vaginal Candida swab, discharge, dyspareunia, soreness, swelling, cyclicity, and exacerbation of symptoms with antibiotics. Conclusions. We propose that CVVC can be confidently diagnosed using the major criteria of a chronic nonspecific and nonerosive vulvovaginitis that includes at least 5 or more properties from the following criteria: soreness, dyspareunia, positive vaginal swab either at presentation or in the past, previous response to antifungal medication, exacerbation with antibiotics, cyclicity, swelling, and dis- charge. This condition responds reliably to oral antifungal medication. h Key Words: vulvovaginal, candidiasis, chronic, diagnosis, definition We have frequently observed a subtype of VVC, common in vulvar disease clinics, in which patients’ symptoms are continuous rather than discretely episodic. In a vulvar clinic situation, acute and even re- current VVC is rarely encountered and we, therefore, presume it is being successfully managed in primary care. In contrast to recurrent vulvovaginal candidiasis (RVVC) where patients are asymptomatic between dis- crete attacks, this third group has an as-yet undefined and uncharacterized condition that we have termed chronic vulvovaginal candidiasis (CVVC). In this condition, pa- tients present with chronic, continuous symptoms, which improve during menses and remit with antifungal ther- apy, often recurring when this is ceased, particularly after short course therapy. We have also observed that vaginal swabs do not invariably demonstrate Candida at pre- sentation even in the presence of intense symptoms and obvious signs and that insisting on this as a diagnostic Reprint requests to: Shreya Dixit, B Med Sci, MBBS(Hons), Department of Dermatology, Royal North Shore Hospital, Reserve Rd, St Leonards, NSW 2065, Australia. E-mail: sdixit177@gmail.com The authors have declared they have no conflicts of interest. Ó 2013, American Society for Colposcopy and Cervical Pathology Journal of Lower Genital Tract Disease, Volume 18, Number 1, 2014, 31Y38 Copyright © 2013 American Society for Colposcopy and Cervical Pathology. Unauthorized reproduction of this article is prohibited.
  2. 2. criterion would limit our ability to identify and correctly treat this condition. Vulvovaginal candidiasis (VVC) is defined as vulvo- vaginitis causally related to vaginal carriage of Candida species and is a common problem associated with a high level of morbidity. The burden of cost to the community is significant and has been estimated at $1.8 billion per year in the United States [1, 2]. Topical and oral anti- fungal medications are readily available over the counter. Many women self-medicate, generating extra costs in medication use and false-negatives when medication has been used before microbiologic confirmation. There are 2 well-described subtypes of VVC that re- late to the duration and frequency of disease: acute and recurrent. In acute VVC, women experience signs and symptoms of acute vaginitis with a heavy white discharge sporadically. Candida is readily cultured from the vagina. Acute VVC is common, estimated to affect up to 75% of women during their lives and is usually easily diagnosed and treated [1]. Recurrent VVC is defined as 4 or more culture-proven episodes per year and is estimated to occur in 5% of women. It is, however, difficult to know accu- rately the true incidence of VVC because of widespread self-diagnosis and self-treatment with over-the-counter preparations [3]. The pathogenic mechanisms of recurrent VVC are still not fully understood, and there is no simple and re- liable diagnostic test. Self-medication may result in false- positives in patients with clinical candidiasis, while, on the other hand, we know that Candida is a commensal in the genital tract, and a positive vaginal swab in the ab- sence of signs and symptoms is without significance. As a result, diagnosis can be surprisingly difficult. Cyclical vulvovaginal itch, discharge, swelling, and pain are typical features that have been previously identified [4]. VVC, like many vulvar diseases, has the potential to cause great psychologic distress and negatively impact a patient’s quality of life (QoL) [5, 6]. This clinical syndrome is the focus of this article in which we propose a definition and diagnostic criteria. METHODS The study was granted approval by the ethics committee of the Northern Sydney Central Coast Area Health Ser- vice and was conducted in 3 stages. Stage 1: Expert Consensus to Establish Inclusion Criteria An online survey (Survey Monkey 2010) was sent to 18 experienced Australian vulvologists, all of whom were members of the Australia and New Zealand Vulvovaginal Society including dermatologists and gynecologists spe- cializing in the treatment of vulvovaginal conditions. Survey participants were asked to choose and rank those clinical and historical features they considered most im- portant in diagnosing candidiasis. There was a 72% re- sponse to the survey. Results are shown in Table 1 and were used to define the selection criteria for the study cohort. Patients with a minimum of 5 of 8 clinical char- acteristics considered characteristic of candidiasis were included in the study. Although a positive vaginal swab for Candida was found in most patients, this was not considered an essential criterion. Stage 2: Cohort Study Between January and August 2010, patients were recruited from a vulvar dermatology disease clinic in a tertiary hospital and a private tertiary referral dermogynecology practice in Sydney, Australia. All patients presenting were screened for eligibility to participate in the study. Inclusion criteria were women aged at least 18 years with nonerosive vulval erythema and a minimum 3-month history of chronic vulvar symptoms including a mini- mum of 5 historical features as established by consensus. A control group was chosen from patients with vulvar erythema due to dermatitis or psoriasis, the appearance of which closely resembles candidiasis on examination and is easily confused clinically with CVVC. We were not able to compare our CVVC patients to those with either acute or recurrent VVC as we rarely encounter these patients in a vulvar clinic situation. A total of 92 patients were included in the study: 50 patients in the study group and 42 patients in the control group. Stage 3: Forward Testing of Diagnostic Criteria Between October 2010 and July 2011, the diagnostic criteria established from the initial study group were then applied prospectively to a further 163 patients to Table 1. Diagnostic Features in CVVC by Expert Consensus Sign/symptom Concordance, % Itch 90 History of improvement with antifungal treatment 90 Dyspareunia 88 Previous positive vaginal swab 86 Soreness 82 Cyclicity 62 Exacerbation with antibiotics 60 Discharge 40 32 & H O N G E T A L . Copyright © 2013 American Society for Colposcopy and Cervical Pathology. Unauthorized reproduction of this article is prohibited.
  3. 3. determine their accuracy. All patients identified using the criteria were fully responsive to oral antifungal therapy. CVVC Questionnaire A 61-item CVVC questionnaire was devised to allow investigators to compare between the study cohort and control groups, clinical features for diagnostic evaluation, demographic data for comparing baseline characteristics, as well as behavioral and QoL data. The QoL questions were modified from the Dermatology Life Quality Index (DLQI), a validated tool used widely in assessing the im- pact of skin diseases such as psoriasis on a patients’ QoL [7]. QoL data are not presented in this article. Study Protocol At the first visit, all patients completed the CVVC Questionnaire. History and vulvar examination findings at baseline were recorded, and a low vaginal swab for Candida was also collected. Patients in the study group were commenced on treatment with a 3-month course of oral antifungal therapy, either fluconazole 50 to 100 mg daily or itraconazole 100 mg daily. Patients in the con- trol group were treated with topical corticosteroid alone as appropriate to their condition. A follow-up visit was conducted for all patients after 3 months where history, questionnaire, and physical examination findings were again recorded, as well as specific treatment type used and clinical response to therapy. The target outcome desired was complete resolution of objective signs and self-reported symptoms. A complete response to the oral antifungal treatment regimen, defined as resolution of symptoms and resolution of objective inflammation, was used as confir- mation of the provisional diagnosis of CVVC. Statistical Analysis Clinical and historical characteristics for the study cohort and the control group were compared to determine sig- nificant differences, sensitivity, specificity, and positive and negative predictive values. Statistical analyses were performed using SPSS v17. For univariate analysis, W2 test and 2-tailed Fisher exact test were used, where values of p G .05 were considered significant and p G .01 were considered highly significant. Multivariable logistic regres- sion and receiver operating characteristic curve analyses were used to determine diagnostic criteria for CVVC. RESULTS The following items relating to signs and symptoms were all significantly more common in the CVVC study cohort compared to the control group (with p e .001): soreness, dyspareunia, cyclicity, vulvovaginal swelling vaginal dis- charge, and positive vaginal swab for Candida. The fol- lowing historical features were all significantly more likely in the CVVC group (p G .001): history of previous positive Candida vaginal swab while symptomatic, ex- acerbation of symptoms with oral antibiotics, and history of improvement with any antifungal treatment even if brief. At the follow-up visit, response to 3 months of oral antifungal therapy was measured. All women with CVVC had complete resolution of signs and symptoms with prolonged daily oral antifungal treatment (p G .001). It should be especially noted that 68% of the study group and 7% of the control group had a positive swab at pre- sentation. This is a significant difference; however, there still remained 32% of patients who were fully responsive to oral antifungal therapy who had a negative swab. Eight clinical and historical features were identified as being significantly more common in the CVVC group (with high statistical significance, p e .001). Table 2 highlights odds ratios (ORs) associated with these fea- tures. Patients in the CVVC group were 79 times more likely to have had a previous positive Candida swab than women in the control group. Exacerbation with oral antibiotics and vaginal discharge were more than 25 times more likely in patients with CVVC. Cyclicity of symptoms and dyspareunia were 17 and 9 times more likely in CVVC, respectively, whereas soreness and Table 2. Statistical Analysis of Criteria V Control Versus CVVC Total no. Cases (n = 50), n (%) Controls (n = 42), n (%) OR (95% CI) a) Previous response to antifungals 92 50 (100) 3 (7.1) n/a b) Previous or current positive swab 92 43 (86.0) 3 (7.1) 79.86 (19.30Y330.5) c) Exacerbation with antibiotics 86 30 (68.2) 3 (7.1) 27.86 (7.33Y105.8) d) Discharge 92 42 (84.0) 7 (16.7) 26.25 (8.66Y79.58) e) Cyclicity 88 30 (65.2) 4 (9.5) 17.81 (5.39Y58.88) f) Dyspareunia 92 43 (86.0) 16 (38.1) 9.98 (3.63Y27.49) g) Soreness 92 44 (88.0) 24 (57.1) 5.50 (1.93Y15.71) h) Swelling 92 31 (62.0) 10 (23.8) 5.22 (2.10Y12.99) Vulvovaginal Candidiasis as a Chronic Disease & 33 Copyright © 2013 American Society for Colposcopy and Cervical Pathology. Unauthorized reproduction of this article is prohibited.
  4. 4. swelling were 5 times more likely to be found in the CVVC group compared to controls. Vulvovaginal itch was not a significant distinguishing feature of CVVC in our study group as it was present in 88% of the control group also. A history of atopy was associated more frequently with the control group (71% vs 50%, p G .05), and more women in the CVVC group reported an improvement of their vulvovaginal symptoms during pregnancy (53% vs 20%, p G .05). However, neither atopic history nor improvement during pregnancy significantly differed between the 2 groups. Qualitative data on suspected risk factors for CVVC were collected and analyzed using a 5-point Likert scale, where 1 = strongly disagree, 2 = disagree, 3 = neither agree or disagree, 4 = agree, and 5 = strongly agree. Mean scores for each item were used to compare the 2 patient groups. Figure 1 summarizes the findings. A mean score less than 3 was represented as a negative value or dis- agreeing with a statement. Mean scores greater than 3 (agreeing with a statement) were represented as positive values. A mean score equal to 3 was interpreted as being ‘‘neutral’’ and assigned a value of zero. Of the 34 patients in the CVVC group that had posi- tive Candida swabs taken at the start of the study, only 1 swab was identified as Candida glabrata, the rest were Candida albicans. A history of a positive Candida swab during the course of their disease was reported in 86% of women in the CVVC group. Figure 1. Hormonal influence on symptoms. Figure 2. Number of criteria met (CVVC vs control). 34 & H O N G E T A L . Copyright © 2013 American Society for Colposcopy and Cervical Pathology. Unauthorized reproduction of this article is prohibited.
  5. 5. A selected multivariable logistic regression analysis of 8 significant features for the identification of CVVC demonstrated 4 criteria (positive swab, cyclicity, soreness, and discharge) to have excellent predictive validity as diagnostic criteria. The corresponding area under the receiver operating characteristic curve was 0.969 (95% confidence interval [CI] = 0.935Y1.00). According to these analyses, patients with any 2 of the 4 aforemen- tioned criteria (except soreness with discharge only) may be accurately classified as having CVVC in this study. The proposed diagnostic criteria gave a sensitiv- ity of 0.90 (95% CI = 0.77Y0.96), specificity of 0.98 (95% CI = 0.86Y1.00), positive predictive value of 0.98 (95% CI = 0.87Y1.00), negative predictive value of 0.89 (95% CI = 0.76Y0.96), and positive likelihood ratio of 37.8 (95% CI = 5.44Y262.7). The 8 historical and clinical features found to be sig- nificant discriminators for CVVC were analyzed further to determine how many features were present for each patient across both groups. Results are summarized in Figure 2. In the CVVC group, no women had fewer than 3 of the 8 criteria. Most CVVC women (88%) fulfilled 4 to 8 of 8 criteria. In the control group, no patients met more than 4 of 8 criteria, whereas 95% of control pa- tients met 0 to 3 criteria only. Table 3 outlines the diag- nostic criteria. These criteria were prospectively applied to a further 163 patients to determine their accuracy. Of these patients, 86.5% fulfilled 1 major and 5 or more minor criteria, and the remainder had a presumptive diagnosis with 3 to 4 minor criteria. All patients (100%) with a definite diagnosis responded to oral antifungal therapy within 3 months. Table 4 compares the percentage of prospectively studied patients with the control group. In both the orig- inal study group and the prospective group, the criteria were found to be highly significant compared to controls. DISCUSSION CVVC seems to exist on a spectrum with acute and re- current variants of VVC but presents as a different entity. We propose that it be defined as a chronic nonerosive vulvovaginitis causally related to Candida. These patients’ symptoms are not recurrent but chronic and continuous, remitting only during treatment with antifungal medica- tion and frequently recurring rapidly on cessation. Our results show that CVVC may be diagnosed using the criteria set out in Table 3. This in turn results in the ability to predict which patients will reliably benefit from oral antifungal treatment. Positive vaginal swabs were found in 68% of women in the original study group and 81.6% of women in the prospective group at the initial visit. Women with CVVC in our study were found to have very low rates of positive microscopy examinations for their swabs, and indeed, the majority had completely normal microscopy. There are a number of possible explanations for these results. The ready availability of over-the-counter antifungal agents used by patients who self-diagnose their CVVC may be responsible. There are no data on how long antifungals should be ceased for before a culture can become positive again, and even if this were available, there is likely to be a wide range between individuals. Women with CVVC may also have lower Candida counts in the vaginal epithelium that trigger symptoms compared to women with more acute forms of VVC. Another possible but less likely explanation is that the Candida strains found in CVVC may differ to those implicit in more acute VVC and may be more fastidious and difficult to culture. In future studies of CVVC, it may be useful to use various media other than CHROMagar for swab cultures and polymerase chain reaction, which has not yet been shown to be more sensitive than culture for Candida detection Table 3. Diagnostic Criteria for Chronic Vulvovaginal Candidiasis & Diagnostic: One major + 5 minor criteria & Presumptive: One major + 3Y4 minor criteria Major Criterion: & Chronic nonerosive, nonspecific vulvovaginitis Minor Criteria: Q5 & Positive vaginal swab either on presentation or in the past & Soreness & Cyclicity & Dyspareunia & Previous response to antifungal therapy even if incomplete & Exacerbation with antibiotics & Swelling & Discharge Table 4. Results From the Prospective Group Compared to the Control Group Diagnostic criteria Prospective (n = 163), n (%) Controls (n = 42), n (%) p Previous response to antifungals 139 (85.3) 3 (7.1) G.0001 Previous or current positive swab 133 (81.6) 3 (7.1) G.0001 Exacerbation with antibiotics 126 (77.3) 3 (7.1) G.0001 Discharge 102 (62.6) 7 (16.7) G.0001 Cyclicity 131 (80.4) 4 (9.5) G.0001 Dyspareunia 153 (93.9) 16 (38.1) G.0001 Soreness 146 (89.6) 24 (57.1) G.0001 Swelling 103 (63.2) 10 (23.8) G.0001 Vulvovaginal Candidiasis as a Chronic Disease & 35 Copyright © 2013 American Society for Colposcopy and Cervical Pathology. Unauthorized reproduction of this article is prohibited.
  6. 6. [8]. Our own experience with Candida polymerase chain reaction reflects this, and we have not found it to be positive unless there is also a positive culture. It is not a routinely available test in Australia and was not per- formed on our study cohort. Sobel [5] reported that low microscopy counts corre- lated with low culture numbers, which, in turn, was as- sociated with asymptomatic carriage of Candida and that high counts correlated with greater severity of signs and symptoms. The patients in our study had highly symp- tomatic disease despite low microscopy counts, which may suggest a hypersensitivity to Candida by these ge- netically susceptible women in producing symptomatic CVVC. Importantly, a positive culture on presentation is not essential for the diagnosis of CVVC provided there are sufficient other diagnostic features present. This is a significant difference from acute and recurrent VVC, which both, by definition, require a positive culture for diagnosis and may support the notion that CVVC is a hypersensitivity reaction, which continues in the absence of detectable Candida in the vagina. There is a possibility that Candida in the bowel may be the antigenic stimulus for a vaginal, estrogen-mediated hypersensitivity response. This could explain why oral antifungal medication is so much more effective than topical vaginal antifungals in treating CVVC. Further investigation is required to ex- plain the possibility of this phenomenon. The pathogenic mechanisms that explain how a nor- mal commensal organism of the genital tract can cause severe chronic symptoms in otherwise healthy women, even in the absence of a positive vaginal swab, remain unknown, and further studies are required to elucidate this. In acute VVC and recurrent VVC (which, by defi- nition, is simply frequent attacks of acute VVC), an in- termittent increase in vaginal Candida colonization, associated with typical signs of acute inflammation (itch, soreness, sudden onset of intense vaginal erythema, typ- ical white cheesy discharge, polymorphonuclear leuko- cytes [PMNs] on vaginal swab, and positive culture for Candida) occurs. A short course of topical or oral anti- fungal medication is usually effective. In CVVC, the clinical picture is quite different. Inflammation, although at times intense, is variable or even absent, particularly during menses. Discharge is frequent but inoffensive and mucoid, lacking in PMNs and usually normal to micros- copy. Symptoms (itch, soreness, dyspareunia) are complex and continuous, flaring premenstrually. Short-course top- ical and oral antifungals afford brief and incomplete relief. It would seem that high estrogen states, which have been highlighted in previous publications as a risk factor, are important [9Y12]. The control group did not report any cyclical change in symptoms, whereas it is charac- teristic of the CVVC group’s symptoms to worsen during the premenstrual phase and improve markedly during menstruation. In addition, CVVC is not seen in prepu- bertal children or postmenopausal women unless the latter are on hormone replacement therapy [13, 14]. Immunodeficiency has been postulated as a factor; however, in this study, all patients were systemically well, were not immunosuppressed, and had no oral involve- ment. A study by Fidel et al. [15] using a live intravaginal Candida challenge showed that patients with candidiasis in fact mount an exaggerated inflammatory response to the organism and also that these patients have a history of previous susceptibility. A lack of inflammation is attributed to protection from symptoms. These data, to- gether with our finding in this study that the presence of a discharge that is not characterized by the presence of polymorphs, may suggest that Candida is behaving as an antigen producing an inflammatory response in geneti- cally susceptible individuals. The difference between this effect in patients with acute or recurrent VVC and CVVC may simply be one of degree; however, this has not been demonstrated. It is possible that there is a threshold be- yond which patients react to Candida in a maladaptive way and that it is lowest in CVVC. Our empirical ob- servation has been that CVVC patients have often, his- torically, evolved from RVVC to CVVC, and we postulate that a diminishing threshold is associated with a progres- sive increase in intolerance of the organism and symp- toms. Prolonged antifungal therapy may be effective in reducing this threshold. The idea that CVVC is a maladaptive inflammatory response rather than an immune deficiency explains par- adoxes that have so far confounded investigators, in- cluding lack of local or systemic immune deficiency, the fact that it is no more common in HIV-infected patients than healthy patients, the lack of oral involvement, and irrelevance of infection by the male partner. Candida antigen interaction with specific estrogen receptors present in vulvovaginal tissue may explain why there is almost never oral involvement, why symptoms cycle, why CVVC is not seen in low estrogen states, and why patients may improve in pregnancy when estrogen receptors are downregulated. Itch was one of the most common presenting com- plaints in both the study (92%) and control (88%) groups, and although it is characteristic, it is nonspecific for VVC. Itch has been used as a diagnostic feature in previous studies of acute and recurrent VVC but was not 36 & H O N G E T A L . Copyright © 2013 American Society for Colposcopy and Cervical Pathology. Unauthorized reproduction of this article is prohibited.
  7. 7. a sensitive marker useful in the diagnosis of CVVC in this study (p 9 .05) [16]. Patients complaining of vaginal itch in the absence of other features should not be assumed to have VVC. We believe this is an important point, as this is a very common assumption. The treatment of chronic and recurrent VVC requires long-term continuous suppressive therapy, often for more than 6 months. Given the lengthy duration of treatment necessary to achieve control of CVVC, oral antifungals are a more attractive option over topicals, less likely to cause irritant reactions, and not significantly more ex- pensive than an equivalent number of antifungal pessaries. Itraconazole and fluconazole are associated with a better liver safety profile compared to ketoconazole (100 mg daily in previous studies), and none of our patients expe- rienced any adverse effects. We have previously empiri- cally observed that daily dosing is more reliable than the widely published treatment regimen of weekly 150 mg of fluconazole, which we have often observed to fail. Thus, women were initially treated with daily itraconazole 100 mg or fluconazole 50 mg, until symptom resolu- tion was achieved, usually approximately 1 to 3 months. Thereafter, a maintenance dose was reached by tapering the dose. The time needed for symptom resolution varied between individuals, but many women were able to maintain symptom control with once- or twice-weekly 50- to 100-mg doses. Women were also instructed to take rescue doses during oral antibiotic treatment, especially if this was a known previous precipitant of flares. Con- comitant antifungal therapy may prevent the flare expe- rienced by some women with CVVC during antibiotic therapy for other infections. Boric acid vaginal supposi- tories (600 mg used twice daily) have been shown to be effective in some treatment-resistant cases of VVC, for example, with C. glabrata colonization, and were used to treat our single patient with C. glabrata on vaginal swab [17]. Given the very large cost burden of treatment of all forms of VVC, it is important to correctly identify patients who will genuinely benefit from treatment. Despite the absence of a placebo control group, the rates of response were much higher than one would expect from placebo effect in correctly selected patients. Donders et al. [18] have called for RVVC to be regarded as a chronic condition. We agree that this is a worthy idea based on the need for prolonged treatment; however, we believe that a condition that behaves chron- ically should be called a chronic condition. There is still a great deal of research that is required to explain both RVVC and CVVC, which may indeed exist on a spectrum. CONCLUSIONS Patients presenting with chronic, erythematous non- erosive vulvovaginitis who answered ‘‘yes’’ to at least 5 of the 8 criteria, which we identified as most characteristic of this condition (Table 3), responded to a 3-month course of oral antifungal medication with complete res- olution of symptoms and signs in 100% of patients. These criteria were subsequently verified in a further group of 163 patients. This included patients with a negative vaginal swab for Candida at presentation. We propose that these diagnostic criteria may be useful in correctly identifying patients who will be genuinely re- sponsive to oral antifungal therapy and that CVVC may be defined as a chronic nonerosive vulvovaginitis causally associated with the antigenic effects of Candida. REFERENCES 1. Foxman B, Barlow R, D’Arcy H, Gillespie B, Sobel JD. Candida vaginitis: self-reported incidence and associated costs. Sex Transmit Dis 2000;27:230Y5. 2. Sobel JD. Vulvovaginal candidiasis. Lancet 2007;369: 1961Y71. 3. Irving G, Miller D, Robinsons A, Reynolds S, Copas AJ. Psychological factors associated with recurrent vaginal candi- diasis: a preliminary study. Sex Transm Infect 1998;74:334Y8. 4. Sobel JD. Pathogenesis and treatment of recurrent vulvovaginal candidiasis. Clin Infect Dis 1992;14(suppl 1): S148Y53. 5. Sobel JD. Candidal vulvovaginitis. Clin Obstet Gynecol 1993;36:153Y65. 6. Powell K. Vaginal thrush: quality of life and treatments. Br J Nurs 2010;19:1106Y11. 7. Finlay AY, Khan GK. Dermatology Life Quality Index. 1991. Available at: http://www.dermatology.org.uk. Accessed June 2010. 8. Mardh PA, Novikova N, Witkin SS, Korneeva I, Rodriques AR. Detection of Candida by polymerase chain reaction vs microscopy and culture in women diagnosed as recurrent vulvovaginal cases. Int J STD AIDS 2003;14:753Y6. 9. Hamad M, Abu-Elteen KH, Ghaleb M. Estrogen- dependent induction of persistent vaginal candidosis in naBve mice. Mycoses 2004;47:304Y309. 10. Sobel JD, Faro S, Force RW, Foxman B, Ledger WJ, Nyirjesy PR, et al. Vulvovaginal candidiasis: epidemiologic, di- agnostic and therapeutic considerations. Am J Obstet Gynecol 1998;178:203Y11. 11. Geiger AM, Foxman B. Risk factors for vulvovaginal candidiasis: a case-control study among university students. Epidemiology 1996;7:182Y7. 12. Calderon L, Williams R, Martinez M, Clemons KV, Stevens DA. Genetic susceptibility to vaginal candidiasis. Med Mycol 2003;41:143Y7. Vulvovaginal Candidiasis as a Chronic Disease & 37 Copyright © 2013 American Society for Colposcopy and Cervical Pathology. Unauthorized reproduction of this article is prohibited.
  8. 8. 13. Fischer G, Bradford J. Vulvovaginal candidiasis in postmenopausal women: the role of hormone replacement therapy. J Low Genit Tract Dis 2011;15:263Y7. 14. Dennerstein GJ, Ellis DH. Oestrogen, glycogen and vag- inal candidiasis. Aust N Z J Obstet Gynaecol 2001;41:326Y8. 15. Fidel PL Jr, Barousse M, Espinosa T, Ficarra M, Sturtevant J, Martin DH, et al. An intravaginal live Candida challenge in humans lead to new hypotheses for the immuno- pathogenesis of vulvovaginal candidiasis. Infect Immun 2004; 72:2939Y46. 16. Nyirjesy P, Peyton C, Weitz MV, Mathew L, Culhane JF. Causes of chronic vaginitis: analysis of a pro- spective database of affected women. Obstet Gynecol 2006; 108:1185Y91. 17. Redondo-Lopez V, Lynch M, Schmitt CA. Torulopsis glabrata vaginitis: clinical aspects and susceptibility to anti- fungal agents. Obstet Gynecol 1990;76:651Y5. 18. Donders GG, Bellen G, Mendling W. Management of recurrent vulvo-vaginal candidosis as a chronic illness. Gynecol Obstet Invest 2010;70:306Y21. 38 & H O N G E T A L . Copyright © 2013 American Society for Colposcopy and Cervical Pathology. Unauthorized reproduction of this article is prohibited.

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