Is it BV? Candidiasis? Trich? A Practical Approach to Making the Diagnosis image

Is it BV? Candidiasis? Trich? A Practical Approach to Making the Diagnosis

Review the latest recommendations with Ashley Fuller, MD, FACOG, NCMP

Dr. Fuller is a gynecologist at Swedish Medical Group in Seattle, WA.  She has a background in microbiology and immunology, with previous work in academic and industry research.  Her practice focuses on vulvovaginal diseases and sexual health.

Learning Objectives: Upon completion of this activity, participants should be better able to

  • Discuss the important components of the evaluation of vaginitis
  • Formulate an evidence-based and practical approach to vaginitis evaluation in practice
  • Describe current testing options and approach to make the diagnosis

CONTENTS:

THE CASE:

Presenting History

  • 32 y/o G1P1
    • Presents with concern regarding vaginal discharge that is thick and white
    • Patient reports 2 weeks of vulvovaginal itching, burning, and discharge
    • Tried OTC vaginal antifungal cream for the past few days which just burned and made it worse
  • Gyn History
    • Same male partner x 5 years
    • Mirena IUD for contraception
    • No history of recurrent vaginal infections but has had BV in the past

SYNOPSIS:

Vaginitis is inflammation or infection of the vagina associated with a spectrum of symptoms and a common reason for visits to both primary care doctors and OB/GYNs.  The majority of these infections will be due to bacterial vaginosis, candidiasis, or trichomoniasis, but noninfectious vaginitis does exist and is not uncommon.  Accurate diagnosis is key as misdiagnosis can cause inappropriate treatment and recurrent visits. There are multiple diagnostic tools available so unfortunately diagnosis is not standardized.  Below are key points to consider for the evaluation, diagnosis, and treatment of vaginitis.

VAGINITIS OVERVIEW:

Bacterial Vaginosis (BV) 

  • Most common diagnosis in patients presenting with vaginal symptoms, especially in reproductive age women
    • 26 to 30% prevalence rate in the US with Black/African American women and Mexican-American with higher rates than non-Hispanic women
  • Associated with
    • Preterm delivery
    • Acquisition of STIs including HIV and PID
    • Complications after gynecologic surgery
    • Douching and sexual activity
  • Pathophysiology
    • Polymicrobial clinical syndrome where anaerobic bacteria (Gardnerella vaginalis, Prevotella sp, Mobiluncus sp, and numerous others) replace normal healthy vaginal Lactobacillus sp. 
    • The lack of hydrogen peroxide producing lactobacillus causes increase in pH
  • Symptoms include
    • Vaginal discharge | Fishy odor
    • Many cases are asymptomatic
  • Recurrence rate: 58% in 12 months

Vulvovaginal Candidiasis (VVC)

  • Second most common diagnosis in patients presenting with vaginal symptoms
    • 75% of women will have at least one episode of VVC in their lifetime
    • 40 to 45% will have >1 episode
  • Most candida infections are caused by Candida albicans but other less common candida species can also cause symptomatic infections
  • Symptoms of VVC include
    • Thick, white discharge | Burning | Itching | Edema | Dyspareunia
  • 10 to 20% of women will have complicated VVC, including recurrent, severe, or nonalbicans candidiasis

Trichomoniasis

  • Caused by the protozoan parasite Trichomonas vaginalis
    • Most common nonviral STI in the United States
    • 13% of black women are affected compared with 1.8% of non-Hispanic white women | CDC considers this gap in infection rates to be reflective of ongoing health disparities
  • Associated with
    • Increased number of sex partners
    • Low socioeconomic status
    • Douching
    • Acquisition of other STIs including HIV, PID, posthysterectomy cuff cellulitis
  • 50% asymptomatic
  • Symptoms include
    • Abnormal discharge | Itching | Burning | Postcoital bleeding | Vaginal or abdominal pain

EVALUATION:

History 

Symptoms: Questions to Ask

  • Characterization: Itching, burning, irritation, dyspareunia, odor, discharge?
    • Consider if symptoms sound more like BV, yeast, or other vaginitis etiology
  • Location of symptoms: Vulvar, vaginal or anal?
    • Consider vulvar or anal dermatologic conditions, such as lichen sclerosus or contact dermatitis
  • Duration: Acute, chronic, or recurrent?
    • Is this a new infection or similar to previous infections?
    • If acute, did something recently change ie antibiotic course for unrelated infection, new sexual partner, new hygiene product?
  • Systemic: Any fever, abdominal pain?
    • Consider PID, UTI, pyelonephritis
  • Urinary symptoms?
    • Consider UTI

Sexual History

  • Number and gender ID of partners
  • Sexual practices | Use of sex toys and washing practices
    • New partner or same sex partner can be associated with BV | Sharing sex toys is associated with BV

Medication History

  • Any self-treatment with OTC products
    • Did OTC treatment help or worsen symptoms? 
    • Could be azole resistant yeast
    • If worsened consider wrong diagnosis or allergic reaction to OTC treatment
    • Can make in-office microscopy more difficult if recent usage of vaginal cream as discharge often mixed with medication

Hygiene Practices

  • Use of detergents, soaps, daily pads
    • Could be associated with contact dermatitis or allergic reaction
  • Douching, shaving
    • Could be associated with BV

Underlying Medical Conditions

  • Diabetes | Contact dermatitis or skin conditions | HIV | Inflammatory bowel disease
    • Uncontrolled diabetes associated with yeast
    • Other skin conditions could make them more likely to have vulvar skin conditions such as eczema
    • HIV infected patients more susceptible to opportunistic infections
    • IBD can be associated with vulvar Crohn’s disease

Relation of Symptoms to Menstrual Cycle

  • Hormonal changes that can affect pH
  • Use of pads or tampons that can cause irritation/allergic reaction

Physical Exam

Step 1: LOOK at the Vulva and Skin Surrounding the Anus

  • Rule out skin dermatosis by evaluating for signs of chronic inflammation
    • Erythema
    • Hypo- or hyperpigmentation
    • Papules and plaques
    • Edema
    • Architectural changes

Step 2: Speculum Exam

  • Obtain samples of vaginal discharge from vaginal walls or fornix
    • BV: Thin | Homogenous | Often with odor
    • Candida: Thick | Chunky | White
    • Trichomonas: Green-yellow | Often bubbly
  • Obtain sample for pH

Clinical ‘Point of Care’ Testing

pH Test

  • Use swab from middle of vagina to avoid collection of semen, cervical mucus
  • Place on narrow-range pH paper
  • Not highly specific
  • BV and Trichomonas have elevated pH > 4.5
  • Candida < 4.5

Wet Mount or Saline Microscopy

  • Coverslips should be placed on the slides and examined at 20x and 40x of microscope in office or laboratory
    • Slide 1: Dilute discharge with 1 to 2 drops of 0.9% normal saline
    • Slide 2: Dilute discharge with 10% KOH (for BV ‘Whiff test’ – see below)
  • Look to identify: Clue cells | Budding yeast/pseudohyphae | Motile trichomonads
  • Test performance
    • Results are immediate, inexpensive
    • Sensitivity | Specificity (broad range due to clinician ability)
    • BV: 37% to 70% | 94 to 99%
    • Candida: 53 to 61% | 89 to 91%
    • Trichomonas: 50 to 75% | 99%
    • Sensitivity increases slightly when in-clinic tests combined with history, signs and symptoms
  • Noninfectious etiologies like desquamative inflammatory vaginitis can ONLY be diagnosed by wet mount
    • Increased number of white blood cells and round parabasal epithelial cells
    • Elevated pH

Note: Many physician offices no longer have microscopes and/or healthcare professionals are not trained at this type of diagnosis

Amsel’s Criteria and KOH Whiff Test (BV)

  • Dilute vaginal discharge with 1-2 drops of 10% KOH and evaluate for amine or “fishy” odor
  • Part of Amsel’s diagnostic criteria for bacterial vaginosis: Must have 3 of the following symptoms/signs
    • Homogenous, thin, white discharge that smoothly coats the vaginal walls
    • >20% Clue cells (vaginal epithelial cells studded with adherent coccobacilli) on microscopic examination
    • pH of vaginal fluid >4.5
    • Positive Whiff Test
  • Sensitivity 92% | Specificity 77% (Amsel’s criteria)
  • Amsel’s criteria is the recommended method of diagnosis (along with Gram stain/Nugent scoring)

Chromogenic BV Test (OSOM BV Blue POC test)

  • Measures sialidase levels in vaginal fluid
  • Sialidase is produced by Gardnerella and Bacteroides
  • Dipstick with results in 10 min
  • Sensitivity 88 to 94% | Specificity  91 to 98%

Rapid antigen test for Trichomonas vaginalis (OSOM Trichomonas POC test)

  • Rapid antigen test to Trichomonas membrane proteins
  • Results in 10 min
  • Sensitivity 88.3% | Specificity 98.8%

Laboratory Testing

Nugent score (BV)

  • Gram stain looking at different types of bacteria associated with BV including
    • Gram positive rods (lactobacilli)
    • Gram negative and gram variable rods and cocci (Gardnerella vaginalis, Prevotella, porphyromonas, peptostreptococci)
    • Curved Gram-negative rods (mobiliuncus)
  • Scores are based on presence of each these bacteria
    • Normal flora: 0 to 3
    • Intermediate flora: 4 to 6
    • BV: 7 to 10
  • Inexpensive | However, usually not same day results
  • Sensitivity 65 to 97% Specificity 71 to 81%

Note: Although recommended for diagnosis, mostly used for research purposes and rarely used in clinical practice

Yeast Culture

  • Indication: Recurrent yeast infections to speciate
    • 10-20% of women have Candida sp. in their vaginas and are asymptomatic so a positive culture without symptoms is not an indication for treatment
    • Can detect specific species
    • Can take several days to a week to get results

Trichomonas culture

  • Not used frequently now that molecular diagnostics are available
    • Less sensitive than newer tests
  • Takes 5 days
  • Sensitivity 75 to 95% | Specificity 100%

Pap Test

  • Do not use for the diagnosis of vaginitis
  • Confirm diagnosis by another method if patient is symptomatic and treat accordingly
  • If asymptomatic with findings suggestive of BV or yeast, no indication to treat
  • If asymptomatic with findings of Trichomonas, perform confirmatory diagnostic test and treat accordingly if positive | Sensitivity only 55 to 60% for trichomonas diagnosis

Commercial Testing

DNA testing (Affirm VP Assay from BD)

  • Direct DNA probe to specific sequences of Gardnerella vaginalis, Candida spp, and Trichomonas
  • Must be sent out to lab
  • However
    • BV: Detection specific for G vaginalis only | Does not test for other bacterial species associated with BV | BV is polymicrobial condition and presence of 1 bacteria does not always indicate BV and can be part of normal flora, lowering specificity
    • Candida: Tests for the presence of several Candida sp. but does not speciate
    • Trichomonas: NAAT is the recommended test (see below) and not DNA testing
  • Sensitivity/Specificity
    • BV: 90.1% | 67.6%
    • Candida: 58.1% | 100%
    • Trichomonas: 46.3% | 100%

Nucleic Acid Amplification Tests (NAAT)

  • Single swab panel test combining nucleic acid probe technology and multiplex PCR
    • Several tests exist including NuSwab (LapCorp), SureSwab (Quest), Aptima (Hologic), BD Max Vaginal panel (Becton Dickinson), OneSwab (Medical Diagnostic Laboratory)
    • Detects BV, Candida and Trichomonas | Can also detect Chlamydia trachomatis and Neisseria gonorrhoeae if desired
    • Must be sent out to lab
  • BV
    • Can detect multiple species of bacteria associated with bacterial vaginosis
    • Most offer detection of common bacterial vaginosis associated bacteria including Atopobium vaginae, fastidious bacteria termed BV-associated bacterium (BVAB2), Megasphera type 1, and G. vaginalis
    • Usually also detect some lactobacilli species that are negative predictors of BV like L. crispatus and L. jensenii
    • The specific species tested varies per brand of test
  • Candida
    • Can detect and speciate multiple species of candida
    • All test for C. albicans and C. glabrata
    • Larger multi species candida test available for C. parapsilosis, C krusei, C tropicalis, C lusitaniae
  • Trichomonas
    • Can detect Trichomonas and is the recommended method for testing
  • Sensitivity/Specificity
    • BV: 90 to 100% | Specificity 91 to 100%
    • Candida: 84.7 to 97.7% | Specificity 93.2 to 99.1%
    • Trichomonas: 95.3 to 100% | Specificity 95.2 to 100%

Professional Recommendations: Diagnostic Clinical Criteria

  • ACOG does describe and recommend point of care testing in the office (summarized below), but also acknowledges that because pH paper, KOH and microscopy may not be generally available

Commercial tests that have been approved by the U.S. Food and Drug Administration (FDA) for the diagnosis of vaginitis can be used as an alternative to clinical testing

BV

  • Amsel’s criteria with saline microscopy and KOH whiff test, and gram stain with Nugent scoring
  • Consider alternative FDA-approved commercial tests

Candida

  • In symptomatic patient must have one of the following
    • Spores, hyphae, or pseudohyphae on saline/KOH microscopy
    • Positive yeast culture
  • Consider alternative FDA-approved commercial tests

Trichomonas

  • NAAT

Back to the Case

  • Exam
    • Vulva: Erythema and edema bilaterally
    • Vaginal: Erythema
    • White discharge present | Some left-over antifungal cream
  • Diagnostic testing
    • PH < 4.5
    • Saline microscopy and KOH: Increased WBCs but no obvious hyphae | More difficult to perform because of antifungal cream in vagina
    • NAAT sent for vaginitis panel of BV, Candida albicans/glabrata, trichomonas
  • Result
    • Candida albicans
  • Treatment
    • Cessation of intravaginal antifungal
    • Patient switched to oral fluconazole

Note: In this case, patient was switched to oral fluconazole because she seemed to have a contact dermatitis from the vaginal anti-fungal | Can happen in approximately 5% of OTC users | Many patients prefer oral anti-fungal as it is equally effective, well tolerated, and allergic reactions are rare 

The Wrap-Up on Diagnostic Testing

  • Accurate diagnosis is important, so avoid treating based on symptoms alone as this approach leads to misdiagnosis and inaccurate treatment which have consequences
    • Increased cost
    • Symptoms continue and return visits are inevitable
    • Loss of trust
    • Ongoing infection that can lead to complications including acquiring HIV or other STIs
    • Overuse of antibiotics for nonexistent bacterial infections that can contribute to vaginal candidiasis and increased risk of azole resistance
  • Self-diagnosis by the patient is not recommended due to limited accuracy
  • Vaginitis may go undiagnosed, so it is important to consider other non-infectious diagnoses such as
    • Vulvar skin diseases | Desquamative inflammatory vaginitis | Genitourinary syndrome of menopause
    • It is important to distinguish vulvar symptoms from vaginal symptoms
  • This patient was evaluated in the office, including a physical exam
    • No evidence of non-infectious cause
    • On wet mount
  • Why was NAAT testing performed?
    • In-office testing with microscopy is quickest but not necessarily most accurate as it depends on both (1) clinician ability and (2) equipment availability
    • For uncomplicated vaginitis especially with a classic presentation, office testing with pH and saline microscopy can be used if trained personnel and well-maintained equipment are both available
    • NAAT test performed in this case because, even in the setting of adequate equipment and trained personnel, the patient had previously failed treatment leaving diagnosis in doubt or necessitating a different approach
    • Especially in the case of more complicated vaginitis presentations (recurrent disease, severe symptoms, or previous failed treatment) consider NAAT as it has higher sensitivity and specificity | Counsel patient that there may be a delay for return of results but that accurate results will determine appropriate treatment

Note: Treatment Guidelines can be found in ‘Related ObG Topics’ below

REFERENCES: 

ACOG Practice Bulletin 215:  Vaginitis in Nonpregnant Patients

Clinical validation of the Aptima Bacterial Vaginosis and Aptima Candida/Trichomonas Vaginitis Assays: Results from a Prospective Multicenter Clinical Study (Schwebke et al. JCM, 2020)

Diagnostic Performance of Molecular test vs clinician assessment of vaginitis (Schwebke et al. JCM, 2018)

Diagnosis and Treatment of Vaginal Discharge Syndromes in Community Practice Settings (Hillier et al.  Clinical Infectious Diseases, 2020)   

Syndromic Treatment of Women with Vulvovaginal Symptoms in the United States: A call to Action! (Sobel, Jack. Clinical Infectious Diseases, 2020) 

Molecular Diagnosis of Bacterial Vaginosis: an Update (Coleman et al, JCM, 2018)

Comparison of Nucleic Acid Amplification Assays with BD Affirm VPIII and Diagnosis of Vaginitis in Symptomatic Women (Cartwright et al. JCM, 2013)

Rapid and POC tests for the diagnosis of Trichomonas Vaginalis in women and men (Gaydos et al. Sexually Transmitted Infections, 2017)

Clinical Validation of a Test for the Diagnosis of Vaginitis (Gaydos et al, Obstetrics and Gynecology, 2017)

Trichomoniasis: CDC Diagnosis and Treatment Guidelines – The ObG Project

Diagnosis and Treatment of Vulvovaginal Candidiasis – The ObG Project

Bacterial Vaginosis – CDC Diagnosis and Treatment Recommendations – The ObG Project

Commercial Support 

This educational activity is supported by Hologic

Faculty Disclosures

Dr. Fuller reports that she has no relevant financial relationships to disclose

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