3.3.2: Inflammatory Disorders of the Vagina

3.3.2.1 Etiology

Vaginitis encompasses both infectious and noninfectious causes. Infectious etiologies include bacterial vaginosis (BV), vulvovaginal candidiasis (VVC), and trichomoniasis, while noninfectious types include atrophic vaginitis, allergic reactions, foreign body, chemical irritation, desquamative inflammatory vaginitis, and lichen planus. Disruption in the normal vaginal microbiota, particularly the reduction of hydrogen peroxide-producing Lactobacillus, is a key factor, often replaced by anaerobic and facultative bacteria such as Gardnerella vaginalis in BV or overgrowth of Candida species in VVC. Contributing factors include hormonal changes, antibiotics, douching, irritants, and tight clothing^.20

3.3.2.2 Epidemiology

Vaginitis is one of the most frequent gynecological complaints worldwide, with BV being the most common, followed by VVC and trichomoniasis. BV affects around 20–30% of reproductive-aged women in the U.S., and candidiasis affects over 30% of women in this age group. Trichomoniasis is the most common non-viral STI globally. Its incidence varies by age, hormonal status, sexual activity, hygiene, and healthcare access. Incidence is higher in low-resource settings and among individuals with risk factors such as poor hygiene, multiple sexual partners, and immunosuppression. Many women use over-the-counter remedies, which makes it difficult to evaluate the incidence of vaginitis accurately. ²¹

3.3.2.3 Pathogenesis

The pathogenesis of vaginitis differs based on the underlying cause. In bacterial vaginosis (BV), the depletion of protective Lactobacillus species permits the overgrowth of anaerobic bacteria such as Gardnerella vaginalis. Vulvovaginal candidiasis (VVC) results from the transformation of Candida from a commensal organism to a pathogen, often triggered by hormonal fluctuations, antibiotic use, or immune suppression. Trichomoniasis arises from direct infection by the protozoan Trichomonas vaginalis. Noninfectious forms may be associated with estrogen deficiency, hypersensitivity reactions, or mechanical irritation. Oxidative stress has emerged as a central mechanism across multiple vaginitis types. Excessive production of reactive oxygen species (ROS), coupled with the depletion of antioxidants like catalase (CAT) and glutathione (GSH), contributes to DNA fragmentation and the oxidation of lipids and proteins. This oxidative imbalance activates pro-inflammatory cytokines (e.g., TNF-α, IL-1β, IL-6) and induces mitochondrial dysfunction, promoting epithelial apoptosis and tissue injury. The resulting inflammatory cascade, marked by leukocyte infiltration and cellular damage, is a key driver of vaginitis pathogenesis.²²

3.3.2.4 Pathophysiology

The vaginal mucosa becomes inflamed, leading to discharge, itching, and pH alterations. The nature of the discharge helps distinguish between different types of vaginitis. For example, foul-smelling discharge occurs in bacterial vaginosis.²³

3.3.2.5 Diagnosis

Accurate diagnosis requires clinical evaluation plus lab confirmation. Tools include pH testing, wet mount microscopy, KOH prep, Gram stain with Nugent score (for BV), culture (especially for Candida species), and molecular assays such as PCR and NAAT. Oxidative stress markers (e.g., MDA, H₂O₂), DNA fragmentation, and apoptosis biomarkers (caspase-3, Bax, cytochrome C) have been correlated with vaginitis severity, but these are primarily used in research settings and not routine clinical diagnostics. The nature of the vaginal discharge is a key diagnostic indicator.²⁴

• Bacterial Vaginosis

Characterized by thin, homogeneous, foul-smelling, often fishy discharge. On microscopy, there are clue cells [vaginal epithelial cells (squamous epithelium) covered with bacteria (gram negative rods)] (Figure 3), and the vaginal pH is elevated (typically >4.5). This is linked to an overgrowth of anaerobic bacteria like Gardnerella vaginalis due to a reduction in Lactobacillus. Amsel's criteria (including pH, clue cells, discharge characteristics, and whiff test) are commonly used for diagnosis. The Nugent score, based on Gram stain, is another diagnostic method. ²⁵

• Vulvovaginal Candidiasis

Often presents with a thick, white, cottage cheese-like discharge. There is erythema of the vagina, and budding yeast or pseudohyphae are detected on KOH prep. Culture may be necessary to identify non-albicans Candida species.²⁶

• Trichomoniasis

Can cause a frothy, yellow-green discharge. There is a strawberry cervix and motile flagellates seen on a wet mount.²⁷

• Desquamative Inflammatory Vaginitis

Manifests as excessive purulent discharge (yellow-greenish), or mixed with blood.²⁸

• Atrophic vaginitis

Clinical features of atrophic vaginitis typically include vaginal dryness, burning, discomfort during intercourse (dyspareunia), and inflammation. On examination, the vaginal mucosa may appear thin with a loss of rugal folds and, in some cases, purulent discharge. Microscopic evaluation of vaginal secretions often reveals numerous white blood cells, occasional basal and parabasal cells, a reduced presence of Lactobacillus species, and an increased number of gram-positive cocci and gram-negative rods. The vaginal pH is commonly elevated above 4.5.²⁹

3.3.2.6 Differential Diagnosis

Vaginitis may mimic STIs (chlamydia, gonorrhea, herpes), UTIs, PID, dermatologic conditions (lichen sclerosus, eczema, psoriasis), vulvodynia, and allergic reactions. Foreign body-induced vaginitis, particularly in children, is another consideration.³⁰

3.3.2.7 Treatment

• Bacterial Vaginosis

  • Recommended: Metronidazole 500 mg orally twice daily for 7 days or intravaginal metronidazole 0.75% gel once daily for 5 days or clindamycin 2% cream intravaginally at bedtime for 7 days.
  • Alternative Regimens: Tinidazole 2 g orally once daily for 2 days or tinidazole 1 g orally once daily for 5 days or clindamycin 300 mg orally twice daily for 7 days.
  • Recurrent BV: May need extended or alternative regimens. Consider suppressive therapy with twice-weekly metronidazole gel. CDC recommends using the same drugs used to treat the initial infection.³¹

Note

Treatment of male partners is not generally recommended.

• Vulvovaginal Candidiasis

  • Uncomplicated VVC:Fluconazole 150 mg single dose orally or topical azoles (e.g., clotrimazole, miconazole) for 1-7 days.
  • Complicated VVC (recurrent, severe, non-albicans): Fluconazole 150 mg orally every 72 hours for three doses, followed by maintenance therapy (e.g., fluconazole 150 mg weekly for six months). Topical treatments may also be used for longer durations.³²

Note

Identify and manage predisposing factors such as uncontrolled diabetes or antibiotic use.

• Trichomoniasis

  • Recommended: Metronidazole 2 g orally in a single dose or tinidazole 2 g orally in a single dose.³³

Note

Treat partners to prevent reinfection. HIV-positive patients may require a 7-day course of metronidazole.

• Atrophic Vaginitis

  • First-line: Vaginal estrogen cream (e.g., conjugated estrogens, estradiol).
  • Non-hormonal options: Vaginal moisturizers and lubricants for mild symptoms.
  • Alternative: Oral ospemifene, an estrogen agonist/antagonist.³⁴

Note

Long-term therapy may be necessary.

• Antioxident Therapy

While promising, antioxidant strategies require further validation through large-scale clinical studies. Vitamin C vaginal tablets have been shown to restore Lactobacillus dominance, reduce vaginal pH, and alleviate symptoms.³⁵

Figure 3.3.3 Two epithelial cells are seen however the one on the left is 'coated' with gram variable bacilli (Gardnerella vaginalis) making the cell appear purplish. On lower power scanning, these are usually seen with some frequency in a patient experiencing bacterial vaginosis.
(1000X, Gram Stain, Nikon). https://thunderhouse4-yuri.blogspot.com/2010/11/bacterial-vaginosis.html
Source: Yuri. Fun With Microbiology (What’s Buggin’ You?): Bacterial Vaginosis.” Accessed April 15, 2025. Open source blog, available from: https://thunderhouse4-yuri.blogspot....vaginosis.html.

Footnotes

21. Hildebrand, Jason P., Karen Carlson, and Adam T. Kansagor. “Vaginitis.” StatPearls, January 19, 2025. https://www.ncbi.nlm.nih.gov/books/NBK470302/; MojganTansaz, Aminimoghaddam Soheila, Hosseini Hamed, Moghadam Fazele Heydarian, and Hajimehdipoor Homa. “Vaginitis: Etiology and Role of Oxidative Stress, Inflammation and Antioxidants Therapy.” Reproductive Medicine International 4, no. 1 (2021). https://doi.org/10.23937/2643-4555/1710014. Mohammed, Lubna, Moiz Javed, Aldanah Althwanay, Farah Ahsan, Federico Oliveri, Harshit K Goud, Zainab Mehkari, and Ian H Rutkofsky. “Live Bacteria Supplementation as Probiotic for Managing Fishy, Odorous Vaginal Discharge Disease of Bacterial Vaginosis: An Alternative Treatment Option?” Cureus, 2020. https://doi.org/10.7759/cureus.12362; Agarwal, Manju, Rakhee Soni, and Adhunika Singh. “Clinical Presentation, Diagnosis and Management of Bacterial Vaginosis: A Hospital Based Cross-Sectional Study.” International Journal of Reproduction, Contraception, Obstetrics and Gynecology 9, no. 4 (2020). https://doi.org/10.18203/2320-1770.ijrcog20201222.
22. Hildebrand et al, 2025; Mojgan et al, 2021; Mohammaed et al, 2020; Agarwal et al, 2020.
23. Hildebrand et al, 2025; Mojgan et al, 2021; Mohammaed et al, 2020; Agarwal et al, 2020.
24. Hildebrand et al, 2025; Mojgan et al, 2021; Mohammaed et al, 2020; Agarwal et al, 2020.
25. Hildebrand et al, 2025; Mojgan et al, 2021; Mohammaed et al, 2020; Agarwal et al, 2020.
26. Hildebrand et al, 2025; Mojgan et al, 2021; Mohammaed et al, 2020; Agarwal et al, 2020.
27. Hildebrand et al, 2025; Mojgan et al, 2021; Mohammaed et al, 2020; Agarwal et al, 2020.
28. Hildebrand et al, 2025; Mojgan et al, 2021; Mohammaed et al, 2020; Agarwal et al, 2020.
29. Hildebrand et al, 2025; Mojgan et al, 2021; Mohammaed et al, 2020; Agarwal et al, 2020.
30. Hildebrand et al, 2025; Mojgan et al, 2021; Mohammaed et al, 2020; Agarwal et al, 2020.
31. Hildebrand et al, 2025; Mojgan et al, 2021; Mohammaed et al, 2020; Agarwal et al, 2020.
32. Hildebrand et al, 2025; Mojgan et al, 2021; Mohammaed et al, 2020; Agarwal et al, 2020.
33. Hildebrand et al, 2025; Mojgan et al, 2021; Mohammaed et al, 2020; Agarwal et al, 2020.
34. Hildebrand et al, 2025; Mojgan et al, 2021; Mohammaed et al, 2020; Agarwal et al, 2020.
35. Hildebrand et al, 2025; Mojgan et al, 2021; Mohammaed et al, 2020; Agarwal et al, 2020.

Image Acknowledgements

Yuri. Fun With Microbiology (What’s Buggin’ You?): Bacterial Vaginosis.” Accessed April 15, 2025. Open source blog, available from: https://thunderhouse4-yuri.blogspot....vaginosis.html.