Candida vulvovaginitis pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Dima Nimri, M.D. [2], Aravind Kuchkuntla, M.B.B.S[3]

Overview

Several virulence factors of Candida are implicated in vulvovaginitis, but the process of transition from asymptomatic vaginal colonization to symptomatic vulvovaginitis is poorly understood. There may be genetic factors associated with Candida vulvovaginitis, as infection runs in families in many cases and is more common in African-American women.

Pathophysiology

Vaginal Defensive mechanisms aganist Candida

Innate Mechanisms

Defense Mechanism of protection Evidence of protection
Vaginal epithelial cells
  • Protective role in vivo unknown
  • Patients with recurrent candida infections have decreased anti-Candida activity
Mannose-binding lectin
Activated lactoferrin[4]
  • Fungistatic and fungicidal activity
  • Role in protection aganist infection is not clear
Vaginal bacterial flora
  • Role in protection aganist vaginitis still unclear
Phagocytic systems/polymononuclear leukocytes, mononuclear cells, complement
  • Role in protection still unclear

Adaptive Mechanisms

Defense Mechanism Role in Protection
Immunoglobulin mediated immunity Systemic IgM, IgG, and local IgA antibodies are produced in response to the infection[6]
  • Protective role not proven.
  • Elevated titres of vaginal anti-Candida IgG, IgA are detected in women with recurrent vaginitis
  • Persistent symptoms could be attributed to anti-Candida IgE[7]
Cell Mediated Immunity

Interleukin 4 (Th2) inhibits anti-Candida activity of nitric oxide and protective pro-inflammatory Th1 cytokines.[8]

  • Role in protection from vulvovaginitis is still not clear
  • It is still a hypothesis[9]
  • Patients with recurrent infection have undetectable Th2 cytokines.

Candida Virulence Factors

Pathogenesis

Genetics

Gross Pathology

On speculum examination typical curdy white discharge is present.

Microscopic Pathology

Microscopic examination of the wet mount with 10% KOH or saline demonstrates hyphae, pseudohyphae and blastospores.

Associated Conditions

  • Candida vulvovaginitis may be associated with other pathogens that cause vulvovaginitis. These include Trichomonas vaginalis and Gardnerella vaginalis. The association may be a mixed infection, where 2 or more pathogens are symptomatic, or a co-infection, in which there are 2 or more pathogens but some are not symptomatic.[22][23]

References

  1. Barousse MM, Espinosa T, Dunlap K, Fidel PL (2005). "Vaginal epithelial cell anti-Candida albicans activity is associated with protection against symptomatic vaginal candidiasis". Infect Immun. 73 (11): 7765–7. doi:10.1128/IAI.73.11.7765-7767.2005. PMC 1273905. PMID 16239581.
  2. 2.0 2.1 Donders GG, Babula O, Bellen G, Linhares IM, Witkin SS (2008). "Mannose-binding lectin gene polymorphism and resistance to therapy in women with recurrent vulvovaginal candidiasis". BJOG. 115 (10): 1225–31. doi:10.1111/j.1471-0528.2008.01830.x. PMID 18715406.
  3. Ip WK, Lau YL (2004). "Role of mannose-binding lectin in the innate defense against Candida albicans: enhancement of complement activation, but lack of opsonic function, in [[phagocytosis]] by human dendritic cells". J Infect Dis. 190 (3): 632–40. doi:10.1086/422397. PMID 15243942. URL–wikilink conflict (help)
  4. Naidu AS, Chen J, Martinez C, Tulpinski J, Pal BK, Fowler RS (2004). "Activated lactoferrin's ability to inhibit Candida growth and block yeast adhesion to the vaginal epithelial monolayer". J Reprod Med. 49 (11): 859–66. PMID 15603095.
  5. Diamond RD, Krzesicki R, Jao W (1978). "Damage to pseudohyphal forms of Candida albicans by neutrophils in the absence of serum in vitro". J Clin Invest. 61 (2): 349–59. doi:10.1172/JCI108945. PMC 372545. PMID 340470.
  6. Waldman RH, Cruz JM, Rowe DS (1972). "Immunoglobulin levels and antibody to Candida albicans in human cervicovaginal secretions". Clin Exp Immunol. 10 (3): 427–34. PMC 1713147. PMID 4556009.
  7. Fidel PL, Sobel JD (1996). "Immunopathogenesis of recurrent vulvovaginal candidiasis". Clin Microbiol Rev. 9 (3): 335–48. PMC 172897. PMID 8809464.
  8. Fidel PL (2005). "Immunity in vaginal candidiasis". Curr Opin Infect Dis. 18 (2): 107–11. PMID 15735412.
  9. Fidel PL, Barousse M, Espinosa T, Ficarra M, Sturtevant J, Martin DH; et al. (2004). "An intravaginal live Candida challenge in humans leads to new hypotheses for the immunopathogenesis of vulvovaginal candidiasis". Infect Immun. 72 (5): 2939–46. PMC 387876. PMID 15102806.
  10. 10.0 10.1 10.2 Sobel JD (2007). "Vulvovaginal candidosis". Lancet. 369 (9577): 1961–71. doi:10.1016/S0140-6736(07)60917-9. PMID 17560449.
  11. 11.0 11.1 11.2 Sobel JD (1985). "Epidemiology and pathogenesis of recurrent vulvovaginal candidiasis". Am. J. Obstet. Gynecol. 152 (7 Pt 2): 924–35. PMID 3895958.
  12. Sobel JD, Muller G, Buckley HR (1984). "Critical role of germ tube formation in the pathogenesis of candidal vaginitis". Infect Immun. 44 (3): 576–80. PMC 263631. PMID 6327527.
  13. 13.0 13.1 Sobel JD (1989). "Pathogenesis of Candida vulvovaginitis". Curr Top Med Mycol. 3: 86–108. PMID 2688924.
  14. Schaller M, Bein M, Korting HC, Baur S, Hamm G, Monod M; et al. (2003). "The secreted aspartyl proteinases Sap1 and Sap2 cause tissue damage in an in vitro model of vaginal candidiasis based on reconstituted human vaginal epithelium". Infect Immun. 71 (6): 3227–34. PMC 155757. PMID 12761103.
  15. Soll DR (1988). "High-frequency switching in Candida albicans and its relations to vaginal candidiasis". Am J Obstet Gynecol. 158 (4): 997–1001. PMID 3284370.
  16. Muzny CA, Schwebke JR (2015). "Biofilms: An Underappreciated Mechanism of Treatment Failure and Recurrence in Vaginal Infections". Clin Infect Dis. 61 (4): 601–6. doi:10.1093/cid/civ353. PMC 4607736. PMID 25935553.
  17. Dennerstein GJ, Ellis DH (2001). "Oestrogen, glycogen and vaginal candidiasis". Aust N Z J Obstet Gynaecol. 41 (3): 326–8. PMID 11592551.
  18. Miles MR, Olsen L, Rogers A (1977). "Recurrent vaginal candidiasis. Importance of an intestinal reservoir". JAMA. 238 (17): 1836–7. PMID 333134.
  19. Fidel PL, Vazquez JA, Sobel JD (1999). "Candida glabrata: review of epidemiology, pathogenesis, and clinical disease with comparison to C. albicans". Clin Microbiol Rev. 12 (1): 80–96. PMC 88907. PMID 9880475.
  20. Calderon L, Williams R, Martinez M, Clemons KV, Stevens DA (2003). "Genetic susceptibility to vaginal candidiasis". Med Mycol. 41 (2): 143–7. PMID 12964847.
  21. Liu F, Liao Q, Liu Z (2006). "Mannose-binding lectin and vulvovaginal candidiasis". Int J Gynaecol Obstet. 92 (1): 43–7. doi:10.1016/j.ijgo.2005.08.024. PMID 16256117.
  22. Sobel JD, Subramanian C, Foxman B, Fairfax M, Gygax SE (2013). "Mixed vaginitis-more than coinfection and with therapeutic implications". Curr Infect Dis Rep. 15 (2): 104–8. doi:10.1007/s11908-013-0325-5. PMID 23354954.
  23. Anderson MR, Klink K, Cohrssen A (2004). "Evaluation of vaginal complaints". JAMA. 291 (11): 1368–79. doi:10.1001/jama.291.11.1368. PMID 15026404.

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