Sandbox: Candida VV
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Synonyms and keywords: Vulvovaginal candidiasis, Candidal Vulvovaginitis, Fungal Vaginitis, Yeast infection, Vulvovaginal Candidosis, candida vaginitis, Genital candidiasis

# Overview
Candida vulvovagintis is an infection of the vagina and the vestibulum, common in women in the reproductive age group. It is caused by various Candida species with Candida albicans most common pathogen followed by other species like Candida glabarta, Candida krusei etc. Patients present with vulvar pruritus, burning micturition and vaginal discharge.The diagnosis of candidal infection requires a collaboration of clinical and diagnostic findings. Patients have typical white cottage chesee like discharge with hyphae and spores demonstrated on microscopy. Patients with uncomplicated infection respond well to topical and oral azole therapy. 5 to 8% of women develop recurrent vaginitis, which is defined as more than 4 episodes in a year. These patients require a longer duration of therapy with an induction and maintenance phase.

# Historical Perspective
- In 1839, B. Lagenbeck from Germany described a yeast-like fungus for the first time in the human oral infection thrush and its ability to cause it.
- In 1923 the Candida albicans was described by Christine Marie Berkhout.  Over the years the classification of the genera and species has evolved. Obsolete names for this genus include Mycotorula and Torulopsis. The species has also been known in the past as Monilia albicans and Oidium albicans. The current classification is nomen conservandum, which means the name is authorized for use by the International Botanical Congress (IBC).
- The full current taxonomic classification is available at Candida albicans.
- The genus Candida includes about 150 different species. However, only a few of those are known to cause human infections. c. albicans is the most significant pathogenic (disease-causing) species. Other Candida species causing diseases in humans include c. tropicalis, c. glabrata, c. krusei, c. parapsilosis, c. dubliniensis, and c. lusitaniae.

# Classification
Candida vulvovaginitis can be classified based on the duration of the infection and based on the strain of Candida causing the infection.

## Duration
Candida vulvovaginitis can be divided based on the duration and number of episodes of the infection into:
- Acute, uncomplicated: these are usually sporadic cases of Candida vulvovaginitis, which respond to topical antifungal therapy and have a high cure rate.
- Acute, complicated: symptoms are more severe than uncomplicated infections and typically require a combination of oral and topical anti-fungal treatment.
- Recurrent Vulvovaginal Candidiasis (RVVC): defined as 4 or more episodes of Candida vulvovaginitis per year, usually caused by the same strain of Candida. Treatment also requires a combination of oral and topical antifungal agents.
- According to 2015, Treatment of STD guidelines - Candida vulvovaginitis can be classified into uncomplicated and complicated based on the following features:

# Pathophysiology

## Vaginal Defensive mechanisms aganist Candida

### Innate Mechanisms

### Adaptive Mechanisms

## Candida Virulence Factors
- C. albicans exists as blastospores, germ tubes, pseudomycelia, true mycelia and chlamydospores on special culture media. C. glabrata exists exclusively in blastospores.
- All strains of Candida species possess a yeast surface mannoprotein which helps in adhering to epithelial cells of the vagina.
- Germination of the spores helps in colonizing the vagina.
- Proteolytic enzymes, toxins and phospholipase destroy the proteins that normally impair fungal invasion, enhancing the ability of Candida to colonize the vagina.
- Phenotypic switching of Candida is described in patients with recurrent vaginitis.
- C. albicans can form biofilms on the intrauterine devices or sponges, causing disease recurrence.

## Pathogenesis
- Candida vulvovaginitis is a microbial disease and not all patients with detectable pathogen are symptomatic. Multiple risk factors and the imbalance in the protective vaginal defenses predispose patients to develop active disease.
- Candida vaginal infections are more common in the reproductive age group because of the high concentration of estrogen as it increases the amount of glycogen in the vagina providing a carbon source for Candida organisms to colonize. It also increases the adherence of Candida to the vaginal epithelial cells.
- The most common source of the infection is from the perianal area. Other less common source is sexual transmission and persistence of organisms in the vagina after treatment which is responsible for recurrence.
- The initial step of infection is colonization and symptoms appear with the invasion of the blastospores or pseudohyphae of the vaginal wall.
- The understanding of the transition from asymptomatic vaginal colonization with Candida to symptomatic vulvovaginitis is not clear.

## Genetics
- Few genetic factors are thought to be involved in patients with recurrent Candida vulvovaginitis.
- Supporting evidence is that Candida vaginitis is common in African-American women, runs in families and its association in patients with ABO-Lewis non-secretor phenotype (a rare blood group).
- In addition, women with recurrent Candida vulvovaginitis were found to have decreased concentrations of mannose binding lectin (MBL), hence, the variant (MBL) gene is thought to be a contributing factor in the development of Candida vulvovaginitis.

## Gross Pathology
On speculum examination typical curdy white discharge is present.
- This photograph is a speculum examination of the vagina with Candida infection and the typical thick, curdy vaginal discharge.

## Microscopic Pathology
Microscopic examination of the wet mount with 10% KOH or saline demonstrates hyphae, pseudohyphae and blastospores.
- This is a a microscopic image of Candida albicans, grown on cornmeal agar medium.
- This higher-power photomicrograph shows the yeasts and pseudohyphae of Candida organisms.
- This high-power photomicrograph shows the yeasts (1) and pseudohyphae (2).

## Associated Conditions
- Candida vulvovaginitis may be associated with other pathogens that cause vulvovaginitis including trichomonas vaginalis and gardnerella vaginalis. The presence of these diseases in combination is common therefore it is important to rule out other etiologies before initiation of anti fungal treatment.

# Causes
Candida vulvovaginitis is caused by many different species of Candida. They are divided into Candida albicans and Candida non-albicans species based on the causative pathogen:

## Common Causes
- Candida albicans: These strains are isolated in 85 to 95% patients with yeast infection.
- Candida non albicans: Candida glabrata is the most common isolated pathogen in this group affecting 10 to 20% of women and is associated with recurrent Candida vulvovaginitis.

## Less Common Causes
These are less commonly isolated in patients but is important to identify the species as they are less sensitive to standard azole therapy and cause recurrent infection.
- Candida parapsilosis
- Candida tropicalis
- Candida krusei

# Differentiating Candida Vulvovaginitis from other Diseases
Candida Vulvovaginitis must be differentiated from the following diseases which have a similar presentation:

# Epidemiology and Demographics
- Epidemiological studies on Candida vulvovaginitis are hard to perform, because of several factors:
Candida vulvovaginitis is not a reportable disease.
The diagnosis of Candida vulvovaginitis is based on clinical presentation and positive laboratory findings. Relying on a positive culture alone would likely overestimate the prevalence of Candida vulvovaginitis.
The use of over-the-counter (OTC) topical anti-fungals makes it difficult to conduct epidemiological studies.
- Candida vulvovaginitis is not a reportable disease.
- The diagnosis of Candida vulvovaginitis is based on clinical presentation and positive laboratory findings. Relying on a positive culture alone would likely overestimate the prevalence of Candida vulvovaginitis.
- The use of over-the-counter (OTC) topical anti-fungals makes it difficult to conduct epidemiological studies.
- Candida is the second most common cause of vaginal infection in young women following bacterial Vaginosis.

## Age
- Incidence of Candida vulvovaginitis is higher in pregnant women.
- Women in reproductive age group are prone for Candida vulvovaginits and at least one episode is reported in 70 to 75% in this population group.
- 40 to 50% of patients with a prior yeast infection have multiple episodes of yeast infection.
- Among the adult population 5 to 8% women have more than four episodes of infection.
- In 20% asymptomatic healthy adolescent women, Candida species can be isolated from the vagina.

## Race
Candida vulvovaginitis is more prevalent among African American women than white American women.

# Risk Factors
The following risk factors have been implicated in predisposing patients to Candida vulvovaginitis:
- Previous infection with Candida vulvovaginitis
- Previous infection with neisseria gonorrhea
- Nulliparity
- Luteal phase of the menstrual cycle 
- Recent antibiotic use
- Pregnancy
- Diabetes mellitus
- Obesity
- Immunosuppression, such as HIV or glucocorticoid use
- Condom use

### Risk Factors for Recurrent Candida Vulvovaginitis
Table adopted from Vulvovaginal candidiasis Lancet 2007; 369: 196171

# Screening
There are no screening procedures for Candida vulvovaginitis.

# Natural History, Complications and Prognosis

## Natural History
Candida vulvovaginitis is a common infection of women in reproductive age group. Patients present with vulvar pruritus, dysuria, and vaginal discharge. Half of the affected patients have multiple episodes of the infection and less than 10% have recurrent infection.

## Prognosis
Candida albicans vulvovaginitis has excellent prognosis with azole therapy. Patients with non-Candida albicans infections are prone to have recurrence and treatment with boric acid and oral fluconazole has good prognosis.

## Complications
Candida vulvovaginitis is a self limiting disease with no complications.

# Diagnosis
Diagnosis of Candida vulvovaginitis requires a correlation of clinical features, microscopic examination, and vaginal culture.

## History and Symptoms
Symptoms of vulvovaginitis caused by Candida species are indistinguishable and include the following:
- Pruritus is the most significant symptom
- Change in the amount and the color of vaginal discharge: It is characterized by a thick, white "cottage cheese-like" vaginal discharge
- Pain on urination (dysuria)
- Pain on sexual intercourse (dyspareunia)
- Vulvovaginal soreness
- Symptoms aggravate a week before the menses

## Physical Examination
Candida vulvovaginitis requires a careful examination of the external genitalia, the vaginal sidewalls and the cervix. Signs include:
- Edema and erythema of the vulva and labia
- Fissures and excoriations of the external genitalia
- Thick whitish vaginal discharge adherent to the vaginal walls
- Cervix is not affected and is normal

## Laboratory Findings
The laboratory findings consistent with the diagnosis of Candida vulvovaginitis include:
- Vaginal pH: vaginal pH is normal (ranges from 4.0-4.5)
- Wet mount or Saline preparation: It will help in detection of hyphae, clue cells and motile trichomonas differentiating different causes of vaginitis.
- 10% Potassium hydroxide preparation: It is more sensitive than wet mount to demonstrate budding blastospores or pseudohyphae.
- Culture: Culture for diagnosing candida vulvovaginitis not recommended in patients with positive microscopy. However, it should be done in a symptomatic woman with a negative microscopy and a normal vaginal pH.  Culture using Sabouraud agar, Nickersons medium, or Microstix-Candida medium identify candida species with equal sensitivity.

## Approach to patient with Candida Vulvovaginitis
The following is a algorithm for diagnosis and treatment of vulvovaginal candidiasis :
Algorithm adopted from Vulvovaginal candidiasis Lancet 2007; 369: 196171

# Treatment

## Medical Therapy
According to, 2016 Update by the Infectious Diseases Society of America medical therapy for Candida vulvovaginitis includes:
- Uncomplicated Candida Vulvovaginits:
1st line :Any topical antifungal agents can be used and all of them have equal efficacy
Alternative : Single 150mg dose of oral fluconazole is recommended
- 1st line :Any topical antifungal agents can be used and all of them have equal efficacy
- Alternative : Single 150mg dose of oral fluconazole is recommended
- Severe acute Candida vulvovaginitis:
1st line: Oral fluconazole 150mg, given every 72 hours for a total of 2 or 3 doses
- 1st line: Oral fluconazole 150mg, given every 72 hours for a total of 2 or 3 doses
- Candida glabrata: When unresponsive to oral azoles
1st line: Topical intravaginal boric acid administered in a gelatin capsule, 600mg daily for 14 days
2nd line: Nystatin intravaginal suppositories, 100,000 units daily for 14 days
3rd line: Topical 17% flucytosine cream alone or in combination with amphotericin B cream daily for 14 days
- 1st line: Topical intravaginal boric acid administered in a gelatin capsule, 600mg daily for 14 days
- 2nd line: Nystatin intravaginal suppositories, 100,000 units daily for 14 days
- 3rd line: Topical 17% flucytosine cream alone or in combination with amphotericin B cream daily for 14 days
- Recurring vulvovaginal candidiasis:
1st line: 10 to 14 days of induction therapy with a topical agent or oral fluconazole, followed by fluconazole, 150mg weekly for 6 months
- 1st line: 10 to 14 days of induction therapy with a topical agent or oral fluconazole, followed by fluconazole, 150mg weekly for 6 months

### Candida Vulvovaginitis in HIV positive women
- Treatment of symptomatic Candida vulvovaginitis  in HIV-positive women is similar to HIV-negative individuals.

## Surgical Therapy
There are no surgical options for Candida vulvovaginitis.

# Prevention

## Primary Prevention
- There are no primary preventive measures for Candidal infection.

## Secondary Prevention
- Prophylactic maintainence of fluconazole is helpful in patients with idiopathic recurrent Candida vulvovaginitis and in secondary recurrent vulvovaginitis associated with lichen sclerosus or topical estrogen application.

# Gallery
- Oral candidiasis on the tongue and soft palate.
- Oral manifestations of HIV infection and AIDS. Chronic oral candidiasis in patient with AIDS. Image courtesy of Professor Peter Anderson DVM PhD and published with permission.  PEIR, University of Alabama at Birmingham, Department of Pathology
- Soft palate showing extensive oral candidiasis in patient with AIDS. Image courtesy of Professor Peter Anderson DVM PhD and published with permission.  PEIR, University of Alabama at Birmingham, Department of Pathology
- Oral candidiasis Image courtesy of Professor Peter Anderson DVM PhD and published with permission.  PEIR, University of Alabama at Birmingham, Department of Pathology
- Eczema secondary to candidiasis. Image courtesy of Professor Peter Anderson DVM PhD and published with permission.  PEIR, University of Alabama at Birmingham, Department of Pathology
- Candidiasis; skinfold. Image courtesy of Professor Peter Anderson DVM PhD and published with permission.  PEIR, University of Alabama at Birmingham, Department of Pathology
- Erythematous candidiasis. Image courtesy of Professor Peter Anderson DVM PhD and published with permission.  PEIR, University of Alabama at Birmingham, Department of Pathology
- Genital candidiasis. Image courtesy of Professor Peter Anderson DVM PhD and published with permission.  PEIR, University of Alabama at Birmingham, Department of Pathology
- Paronychia: Another manifestation of candidiasis. Image courtesy of Professor Peter Anderson DVM PhD and published with permission.  PEIR, University of Alabama at Birmingham, Department of Pathology
- Interdigital candidiasis. Image courtesy of Professor Peter Anderson DVM PhD and published with permission.  PEIR, University of Alabama at Birmingham, Department of Pathology
- Candidiasis of umblical cord. White spots of colonies are present. Image courtesy of Professor Peter Anderson DVM PhD and published with permission.  PEIR, University of Alabama at Birmingham, Department of Pathology
- Lung: Candidiasis. Postmortem findings. Image courtesy of Professor Peter Anderson DVM PhD and published with permission.  PEIR, University of Alabama at Birmingham, Department of Pathology
Image: Candidiasis 17.jpeg|  Candidiasis of the fingernail caused by a fungus of the genus Candida. From Public Health Image Library (PHIL). 

### Skin folds
- Candidiasis. Adapted from Dermatology Atlas.
- Candidiasis. Adapted from Dermatology Atlas.

### Genitourinary
- Infant presented with a rash formerly known as Moniliasis now called Candidiasis caused by the fungus Candida sp. From Public Health Image Library (PHIL). 
- Wet mounted vaginal smear specimen, revealed the presence of Candida albicans, which had been extracted from a patient with vaginal candidiasis. From Public Health Image Library (PHIL). 
- Candidiasis. Adapted from Dermatology Atlas.
- Candidiasis. Adapted from Dermatology Atlas.
- Candidiasis. Adapted from Dermatology Atlas.
- Candidiasis. Adapted from Dermatology Atlas.
- Candidiasis. Adapted from Dermatology Atlas.

### Oral cavity
- Candidiasis. Adapted from Dermatology Atlas.
- Candidiasis. Adapted from Dermatology Atlas.
- Candidiasis. Adapted from Dermatology Atlas.