Candidiasis - Current concepts of etiology, pathogenesis and treatment of vulvovaginal candidiasis

Vaginal discharge is one of the most frequent causes of treatment of women by doctors specialized medical institutions. The cause of vaginal discharge can be as specific (urogenital trichomoniasis), and nonspecific urogenital infections (vulvovaginal candidiasis, bacterial vaginosis, nonspecific vaginitis, desquamative vaginitis, and allergic) and cervicitis of different etiology.

The development of recurrent VVC, defined as four episodes of illness and more than a year, is seen in 5-10% of women [21]. Number of studies [9, 12] demonstrated that Candida ═ spp. can be isolated from the lower parts of the urinary tract in 20% (according to some studies, up to 55%) of women with no abnormal discharge or other symptoms of vulvovaginitis.

It is known that Candida can cause about 20 species of Candida. 85 to 90% of strains of yeasts isolated from the vagina are C. albicans, among non-albicans species of Candida most frequently encountered ═ glabrata ═ (4-4,2%). Next in frequency of occurrence of pathogens are S. FINE parapsilosis ═ (2.26%), C. tropicalis ═ (0,97-1%), C. krusei ═ (0.32%) [22]. Much less frequently isolated C. kefyr, C. guilliermondi, yet at least - other species, but virtually any kind of Candida ═ may be the cause of vulvovaginitis [2, 6].

According to some authors [12, 21], non-albicans species can cause clinically similar to C. albicans ═ vaginitis, but they are characterized by resistance to azole drugs. Other foreign workers [23] include SSC caused by non-albicans species, the so-called uncomplicated vulvovaginal constituting approximately 10% of cases of this disease. For complicated vulvovaginitis tend more severe, recurrent nature of the disease, often manifested by symptoms of diabetes.

Among the reports of non-albicans vulvovaginitah dominated cases caused by C. glabrata. It remains controversial whether the increase in such cases, absolute, or reflect the growth of cultural studies as compared with routine microscopic methods.

The researchers found that the fungi of the genus Candida ═ typical dimorphism - one of the major virulence factors, which is manifested by alternating mycelial and yeast phases of the life cycle, as demonstrated by the wide possibilities of adaptation of agent [6]. The presence of mycelial phase colonies can best absorb and utilize nutrients from the environment, especially when they are scarce. Under favorable conditions, a change of mycelial phase to yeast, characterized by the multiplication by budding. Change of phases is accompanied by a change in the structure of the cell wall, as well as the synthesis of various proteolytic enzymes.

Distinguish the following stages in the development of Candida infection: attachment of fungi to the mucosal surface (adhesion), the increase of the pathogen (colonization), the introduction of the epithelium (invasion), to overcome the barrier of the epithelial mucosa, entering the connective tissue of lamina propria, bridging tissue cellular defense mechanisms penetration into the vascular bed with subsequent dissemination and lesions of various organs. The emergence of symptoms due to inflammatory reaction of tissue response to invasion, as well as various virulence factors of the microorganism. It is known that the pathogenicity of C. albicans ═ the following factors: adhesion to epithelial and endothelial cells, proteinase production, hyphal formation and psevdogif, switching phenotype, production of phospholipases and antigenic modulation as a result of the formation psevdogif [19, 20, 24].

Currently, there is growing resistance of pathogens Candida to antimycotic agents. According to several authors resistant C. albicans ═ the most widely used in Russia, an antifungal agent fluconazole is about 2.3%. C. glabrata ═ most distinguished women who receive prophylactic treatment with fluconazole in low doses. This reflects the view of some scholars on the relationship of cases to increase non-albicans vulvovaginitis and ═ use of short courses of drugs azole, both local and systemic effects.

Although the clinical manifestations of VVC often occur without clearly defined reasons, there are several factors contributing to the development of this disease. It is known that during pregnancy there is increased sensitivity of the vaginal mucosa to Candida ═ spp., manifested in the increase in the number of colonies and the frequency of clinical symptoms of vulvovaginitis. Increased level of sex hormones increases the amount of glycogen in the vaginal epithelium, which is a carbon source for Candida. A number of researchers [15, 16] demonstrated in ═ vitro ═ ability of receptors C. albicans ═ to interact with the female sex hormone that stimulates the formation of mycelium and contributes to clinical manifestations. Pregnant symptoms of VVC most often found in the III trimester.

According to some researchers found an increase in the number of colonies of Candida vaginal ═ spp. through the use of estrogen oral contraceptives. In other studies [7] also found that the development of clinical manifestations of disease contributes to the use of intrauterine devices (IUDs), diaphragms, sponges, condoms, spermicides.

SSC is not normally considered as infection, sexually transmitted, because of the fungi of the genus Candida ═ in the vaginal flora was normal. Earlier in his clinical observations, we found that sexual transmission of infection occurs in men and is rare in women [4]. The number of episodes of VVC does not depend on the number of sexual partners during their lifetime or the frequency of contacts, but may be related to sexual practices (including oral-genital forms of sexual intercourse) [11].

Development of Candida infection by a variety of immunosupres-Intense states including HIV infection. It is not no difference between infected and healthy women at risk of urogenital candidiasis [19]. Moreover, recurrent VVC occurs more frequently in patients who do not have HIV.

It is known that the use of antibiotics broad-spectrum accompanied by the growth of vaginal colonization by Candida ═ spp. and the appearance of clinical symptoms of vulvovaginitis. This process involves the elimination of protective vaginal microflora that provides colonization resistance and prevent the invasion of Candida ═ [18].

A number of studies [8, 17] have shown that SSC bowl found in patients with diabetes mellitus. Elevated blood glucose levels in these patients reduces the phagocytic activity of neutrophils, as well as being nutritious substrate, promotes the growth of colonies Candida. In patients with diabetes mellitus type II being devoted non-albicans vulvovaginitis pathogens, especially C. glabrata ═ [14]. C. glabrata ═ resistant to antifungal azole, particularly to fluconazole, often causing nosocomial infections.

Several clinical studies to identify risk factors for the development of VVC caused by C. glabrata. Such factors include advanced age, uncontrolled diabetes mellitus, previous long-term prophylactic treatment with fluconazole in low doses.

In A. Spinillo et al. [25] also observed peculiarities of vulvovaginitis caused by C. Glabrata. Ratio between C. Albicans ═ and C. gla - brata ═ as causative agents of disease in women of childbearing age was 10:1, in postmenopausal women - 3:1. These figures are explained by a stimulating effect of estrogen on the growth and adhesion to cells of vaginal epithelium C. albicans. In that study, C. glabrata ═ most often stood in HIV-positive women. Was also determined for recurrent vulvovaginitis caused by C. glabrata, which was caused by treatment failure due to resistance of a microorganism to antimycotic azole drugs.

The clinical picture of vulvovaginitis caused by C. glabrata, were more common complaints of pain during sexual intercourse, but much less - the itch. Complaints of vaginal discharge were observed equally often in patients with known C. albicans ═ and C. glabrata. In a study of vulvar erythema and edema occurred with similar frequency in both groups. Physical examination of patients with C. glabrata ═ was characterized by erythema of the vaginal walls and the predominance of white curd-like discharge of separated character (mucous, watery, purulent, frothy).

Another frequently isolated non-albicans species is C. parapsilosis. According to the Russian authors [3], the clinical picture of disease caused by this pathogen is characterized by sparse clear mucus vaginal discharge, mild inflammation (redness, swelling). The same authors have identified features of the flow vulvovaginitis caused by C. tropicalis. The clinical picture is dominated by diseases such complaints of itching in the vulva, cheesy or creamy white discharge, mild hyperemia and marked edema of the mucous membrane of the vulva and vagina. We also know that this kind are often resistant to fluconazole.

Therapy of vulvovaginal candidiasis should be comprehensive, phased, include not only etiotropic treatment, but also the elimination of predisposing factors, and treatment of opportunistic diseases. The objective is to maximize the total elimination of the pathogen. Dose and duration of treatment depend on clinical course and evaluate the effectiveness of the therapy.

The choice of method of treatment depends on many factors: the form of the disease, the general condition of patients, the priorities of patients and physicians.

Distinguish between local and systemic therapies. The benefits of local products is that they are practically not absorbed, creating a high concentration of antimycotics on the mucous membrane, provide a rapid decrease in clinical symptoms. Therefore, their use is justified in pregnancy and lactation.

The disadvantage of local therapy include the uneven distribution of the drug on the surface of the mucous membrane, which creates conditions for the preservation of the reservoir of infection. In this case the system is not ensured elimination of Candida infections in other reservoirs, which can lead to recurrence of infection. Many patients point to the inconvenience of use, which reduces the quality of life. These failures of local resources determine the relevance of systemic therapy.

The advantage of systemic antimycotics is the high efficiency of treatment, the distribution in many organs and tissues, and thus - the impact on the agent in any location. One important advantage of systemic antimycotics is easy to use compared to local vaginal forms.

Treatment regimens of acute systemic candidiasis vulvovaginalnita antimycotics:

╥ Itraconazole (mikotroks) 200 mg 2 times daily for 1 day or 200 mg once daily for 3 days;

╥ Fluconazole (difloks) 150 mg orally once.

Systemic antimycotics for the treatment of chronic SSC (main course):

╥ Itraconazole (mikotroks) 200 mg 1 time per day 3-7 days;

╥ Fluconazole (difloks) 150 mg 3 times at intervals of 72 hours

╥ Ketoconazole 200 mg 2 times a day, 5 days.

Prevention of recurrence of chronic relapsing Candida vulvovaginalnita:

╥ Itraconazole (mikotroks) 200 mg once a day once in a day of menstruation of 4-6 months;

╥ Fluconazole (difloks) 100-150 1 mg once a week, 6 months, then the 1st day of menstruation 6 months;

╥ Ketoconazole 100 mg 1 time per week 6 months.

System candidiasis therapy should be administered, taking into account the sensitivity of the pathogen. For example, Candida ═ non-albicans (C. glabrata, C. tropicalis, C. p. arapsilosis) genetically stable fluconazole. So, if you hold the culture diagnosis is not possible, treatment should be antimycotics widest possible range of actions - itraconazole ("Mikotroksom"). In addition to broad-spectrum, highly lipophilic mikotroks therefore retained in tissues after administration of the drug for 3 days, ensuring the elimination of the pathogen.

A common mistake is to assign the treatment of Candida polyene antimycotics vulvovaginalnita - nystatin, levorin, natamycin as a "systemic" drugs. Their bioavailability is less than 5%, so the outside of the gastrointestinal tract, these antimycotics ineffective.

The results of our own studies on the use of itraconazole ("Mikotroks", manufactured by Pharmacare Int.Co,) in the treatment of vulvovaginal candidiasis published previously, indicate a high efficacy and good tolerability (EA Levonchuk, 2007). We observed 26 patients with vulvovaginal candidiasis: in 9 of them are diagnosed with acute, 17 - chronic recurrent VVC. Allocation for bacteriological examination in 23 patients with C. Albicans, in 2 - C. Tropicalis, in a - C. Crusei confirms the significant prevalence of fluconazole-resistant C an dida ═ non-albicans, which were detected in 13% of patients with recurrent disease.

Patients prescribed therapy schemes proposed above, in accordance with the form of a pathological process that led to the resolution of the pathological process in the first two days in all patients with acute candidiasis, and 7 - chronic. The remaining 10 patients recovery occurred by the end of primary treatment. All patients tolerated the therapy well. Against the background of preventive therapy for relapse in 11 patients not observed in 6 had a slight worsening of the disease before the menstrual period, which did not require appointment of additional therapy.

Thus, studies have shown a high efficacy and good tolerability of systemic antimycotics in the treatment of mikotroksa various forms of vulvovaginal candidiasis. Ease of use and lack of side effects makes it possible to recommend Mikotroks not only for treatment but for prevention of recurrent candidiasis. Patients with recurrent vulvovaginal candidiasis, when it is impossible to culture diagnosis, treatment should be favored itraconazole (Mikotroksu).

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