title: Elevated nitric oxide in recurrent vulvovaginal candidiasis - association with clinical findings.
abstract: BACKGROUND
  Recurrent vulvovaginal candidiasis is defined as having three to four episodes per year and causes substantial suffering. Little is known about the mechanisms leading to relapses in otherwise healthy women. Nitric oxide is part of the nonspecific host defense and is increased during inflammation. Nitric oxide levels were measured and the expression of inducible nitric oxide synthase was analyzed in the vagina during an acute episode of recurrent vulvovaginal candidiasis and after treatment with fluconazole.
  
  
  METHODS
  Twenty-eight women with symptoms of recurrent vulvovaginal candidiasis were enrolled together with 31 healthy controls. Nitric oxide was measured with an air-filled 25-mL silicon catheter balloon incubated in the vagina for five minutes and then analyzed by chemiluminescence technique. Vaginal biopsies were analyzed for the expression of inducible nitric oxide synthase. Symptoms and clinical findings were surveyed using a scoring system. The measurements and biopsies were repeated in patients after six weeks of fluconazole treatment.
  
  
  RESULTS
  Nitric oxide levels were increased during acute infection (median 352 ppb) compared with controls (median 6 ppb), p < 0.0001. The levels decreased after treatment (median 18 ppb) but were still higher than in controls. Increased expression of inducible nitric oxide synthase was observed in the epithelial basal layer in patients before and after treatment compared with controls. Before treatment, there were positive correlations between nitric oxide and symptom (rs= 0.644) and examination scores (rs= 0.677), p < 0.001.
  
  
  CONCLUSIONS
  Nitric oxide is significantly elevated in patients with recurrent vulvovaginal candidiasis during acute episodes of infection and decreases after antifungal treatment. The results illustrate the pronounced inflammatory response in recurrent vulvovaginal candidiasis correlating to symptoms of pain and discomfort.
authors.affiliation: Department of Clinical Sciences, Division of Obstetrics and Gynecology, Karolinska Institute, Danderyd Hospital, Stockholmn, Sweden.
authors.forename: Cathrin
authors.identifier: http://orcid.org/0000-0003-4329-9965
authors.initials: C
authors.lastname: Alvendal
authors.affiliation: Department of Clinical Sciences, Division of Obstetrics and Gynecology, Karolinska Institute, Danderyd Hospital, Stockholmn, Sweden.
authors.forename: Sophia
authors.initials: S
authors.lastname: Ehrström
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Division of Clinical Microbiology, Karolinska Institute and Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Annelie
authors.initials: A
authors.lastname: Brauner
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
authors.forename: Jon O
authors.initials: JO
authors.lastname: Lundberg
authors.affiliation: Department of Clinical Sciences, Division of Obstetrics and Gynecology, Karolinska Institute, Danderyd Hospital, Stockholmn, Sweden.
authors.forename: Nina
authors.initials: N
authors.lastname: Bohm-Starke
mesh_terms: D000293:Adolescent; D000328:Adult; D000935:Antifungal Agents / Q000008:administration & dosage / Q000627:therapeutic use; D002181:Candidiasis, Vulvovaginal / Q000188:drug therapy / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D015725:Fluconazole / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D012008:Recurrence; D011795:Surveys and Questionnaires; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; D009569:Nitric Oxide; D015725:Fluconazole; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II
keywords: Candida albicans; anti-fungal; fluconazole; inducible nitric oxide synthase; nitric oxide; recurrent vulvovaginal candidiasis; vulvovaginal candidiasis