Chronic Vulvovaginal Candidiasis
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《新英格兰医药杂志》
Vulvovaginal symptoms are common, and they represent one of the most frequent reasons for visits to physicians by women in all age groups. Vulvovaginitis is rarely life-threatening, and it is therefore vastly understudied and poorly understood. However, it is associated with substantial, albeit poorly quantified, cumulative morbidity. It causes genital discomfort, loss of productivity, reduced sexual pleasure, and psychological distress and necessitates medical expenditures.
Noninfectious vulvovaginitis is caused by a wide variety of inflammatory, hypersensitivity, and collagen vascular conditions.1 The most common cause of infectious vulvovaginitis is candidiasis, which accounts for 40 to 50 percent of all cases. Vulvovaginitis primarily affects the vulvar skin, the vagina, or a combination of the two. In candidiasis, both the vulvar skin and the vaginal epithelium are usually involved. In most patients, vulvovaginal candidiasis is uncomplicated (see Table). When properly diagnosed, uncomplicated candidiasis may be treated easily and reliably with any number of azole anticandidal medications, including short-course regimens. However, successful treatment is often delayed because the causes of vulvovaginitis, including candidiasis, are commonly misdiagnosed both by patients and physicians2 — mainly because the symptoms and signs may be nonspecific, but also because of the lack of inexpensive and accurate diagnostic tests and because of suboptimal medical training.
Table. Classification of Candidal Vaginitis.
Complicated candidiasis is much less common than uncomplicated disease (see Table). Severe symptoms usually require 7 to 14 days of therapy instead of the short course used for uncomplicated candidiasis. Candida species other than Candida albicans account for only about 10 percent of all infections, but only about half of these infections respond to either oral or vaginal azole therapy. Patients with chronic, recurrent candidiasis account for the remainder of cases of complicated candidiasis. Most cases of recurrent candidiasis are caused by C. albicans. The problem for both patients and physicians is that although complicated candida vulvovaginitis affects only a small proportion of cases of candidiasis, it leads to a substantial percentage of the total physician visits, because the symptoms and the disease usually clear only with very specific therapy or repeated treatment.
In this issue of the Journal, Sobel et al. (pages 876–883) report on the treatment of an important subgroup of women with candida infections, the 5 to 8 percent with chronic, recurrent vulvovaginal candidiasis, defined as four or more episodes per year. This is a manageable form of complicated candidiasis (see Table), and the report, confirming the findings of smaller studies, shows that three doses of fluconazole given at three-day intervals, followed by a single weekly dose, interrupts recurrent candidiasis for six months (the duration of treatment in this study) in more than 90 percent of study participants, as compared with only 36 percent of those given three doses of fluconazole followed by weekly placebo. Local intravaginal azole therapy given once or twice a week is also effective for recurrent candidiasis, but it is more cumbersome to use and is less popular with patients than the oral regimen. Fluconazole was well tolerated and safe, unlike long-term ketoconazole therapy, which has potential liver toxicity. Unlike antibiotics that are given to suppress chronic urinary tract infections, six months of fluconazole treatment did not cause resistance to fluconazole in these women with normal immune function. Such resistance has been a problem when fluconazole has been given on a long-term basis to patients with depressed immune function from human immunodeficiency virus infection. Prolonged suppressive therapy is now the standard of care for chronic, recurrent candida vulvovaginitis, and managed care groups need to start authorizing payment for prolonged suppressive therapy with fluconazole or intravaginal azoles.
Among the patients in the fluconazole group in the study by Sobel et al., about 9 percent had recurrent candida infection despite weekly fluconazole suppression, and within six months after suppression ceased, recurrent infection had developed in 57 percent. The failure to eradicate candida accounted for some recurrent symptoms, and in a separate report, this research group found a few behavioral factors to be loosely associated with recurrence.3 However, in large part, recurrence after stopping suppressive therapy with fluconazole remains unstudied and unexplained.
Thus, a number of questions remain. The optimal duration of suppressive therapy is unknown, and the pathophysiology of chronic, recurrent vulvovaginal candidiasis remains unclear. Some patients with persistent candida infection did not have recurrent symptomatic disease, whereas other patients in whom cultures showed no candida had recurrent symptoms. The role of mucosal immunity in protecting against recurrence, on the one hand, or in generating an excessive response resulting in symptoms despite a low concentration of candida, on the other hand, requires exploration, as do virulence factors on the microbe itself. Further work is required to eradicate this troublesome condition, but the current report describes an effective treatment strategy for the time being.
Dr. Eschenbach reports having received consultation fees from 3M and Pfizer.
Source Information
From the Department of Obstetrics and Gynecology, University of Washington Medical Center, Seattle.
References
Sobel JD. Vaginitis. N Engl J Med 1997;337:1896-1903.
Ferris DG, Nyirjesy P, Sobel JD, Soper D, Pavletic A, Litaker MS. Over-the-counter antifungal drug misuse associated with patient-diagnosed vulvovaginal candidiasis. Obstet Gynecol 2002;99:419-425.
Patel DA, Gillespie B, Sobel JD, et al. Risk factors for recurrent vulvovaginal candidiasis in women receiving maintenance antifungal therapy: results of a prospective cohort study. Am J Obstet Gynecol 2004;190:644-653.
Related Letters:
Chronic Vulvovaginal Candidiasis
Kuebrich C. T., Retzer D. R., Sobel J. D., Eschenbach D. A.(David A. Eschenbach, M.D.)
Noninfectious vulvovaginitis is caused by a wide variety of inflammatory, hypersensitivity, and collagen vascular conditions.1 The most common cause of infectious vulvovaginitis is candidiasis, which accounts for 40 to 50 percent of all cases. Vulvovaginitis primarily affects the vulvar skin, the vagina, or a combination of the two. In candidiasis, both the vulvar skin and the vaginal epithelium are usually involved. In most patients, vulvovaginal candidiasis is uncomplicated (see Table). When properly diagnosed, uncomplicated candidiasis may be treated easily and reliably with any number of azole anticandidal medications, including short-course regimens. However, successful treatment is often delayed because the causes of vulvovaginitis, including candidiasis, are commonly misdiagnosed both by patients and physicians2 — mainly because the symptoms and signs may be nonspecific, but also because of the lack of inexpensive and accurate diagnostic tests and because of suboptimal medical training.
Table. Classification of Candidal Vaginitis.
Complicated candidiasis is much less common than uncomplicated disease (see Table). Severe symptoms usually require 7 to 14 days of therapy instead of the short course used for uncomplicated candidiasis. Candida species other than Candida albicans account for only about 10 percent of all infections, but only about half of these infections respond to either oral or vaginal azole therapy. Patients with chronic, recurrent candidiasis account for the remainder of cases of complicated candidiasis. Most cases of recurrent candidiasis are caused by C. albicans. The problem for both patients and physicians is that although complicated candida vulvovaginitis affects only a small proportion of cases of candidiasis, it leads to a substantial percentage of the total physician visits, because the symptoms and the disease usually clear only with very specific therapy or repeated treatment.
In this issue of the Journal, Sobel et al. (pages 876–883) report on the treatment of an important subgroup of women with candida infections, the 5 to 8 percent with chronic, recurrent vulvovaginal candidiasis, defined as four or more episodes per year. This is a manageable form of complicated candidiasis (see Table), and the report, confirming the findings of smaller studies, shows that three doses of fluconazole given at three-day intervals, followed by a single weekly dose, interrupts recurrent candidiasis for six months (the duration of treatment in this study) in more than 90 percent of study participants, as compared with only 36 percent of those given three doses of fluconazole followed by weekly placebo. Local intravaginal azole therapy given once or twice a week is also effective for recurrent candidiasis, but it is more cumbersome to use and is less popular with patients than the oral regimen. Fluconazole was well tolerated and safe, unlike long-term ketoconazole therapy, which has potential liver toxicity. Unlike antibiotics that are given to suppress chronic urinary tract infections, six months of fluconazole treatment did not cause resistance to fluconazole in these women with normal immune function. Such resistance has been a problem when fluconazole has been given on a long-term basis to patients with depressed immune function from human immunodeficiency virus infection. Prolonged suppressive therapy is now the standard of care for chronic, recurrent candida vulvovaginitis, and managed care groups need to start authorizing payment for prolonged suppressive therapy with fluconazole or intravaginal azoles.
Among the patients in the fluconazole group in the study by Sobel et al., about 9 percent had recurrent candida infection despite weekly fluconazole suppression, and within six months after suppression ceased, recurrent infection had developed in 57 percent. The failure to eradicate candida accounted for some recurrent symptoms, and in a separate report, this research group found a few behavioral factors to be loosely associated with recurrence.3 However, in large part, recurrence after stopping suppressive therapy with fluconazole remains unstudied and unexplained.
Thus, a number of questions remain. The optimal duration of suppressive therapy is unknown, and the pathophysiology of chronic, recurrent vulvovaginal candidiasis remains unclear. Some patients with persistent candida infection did not have recurrent symptomatic disease, whereas other patients in whom cultures showed no candida had recurrent symptoms. The role of mucosal immunity in protecting against recurrence, on the one hand, or in generating an excessive response resulting in symptoms despite a low concentration of candida, on the other hand, requires exploration, as do virulence factors on the microbe itself. Further work is required to eradicate this troublesome condition, but the current report describes an effective treatment strategy for the time being.
Dr. Eschenbach reports having received consultation fees from 3M and Pfizer.
Source Information
From the Department of Obstetrics and Gynecology, University of Washington Medical Center, Seattle.
References
Sobel JD. Vaginitis. N Engl J Med 1997;337:1896-1903.
Ferris DG, Nyirjesy P, Sobel JD, Soper D, Pavletic A, Litaker MS. Over-the-counter antifungal drug misuse associated with patient-diagnosed vulvovaginal candidiasis. Obstet Gynecol 2002;99:419-425.
Patel DA, Gillespie B, Sobel JD, et al. Risk factors for recurrent vulvovaginal candidiasis in women receiving maintenance antifungal therapy: results of a prospective cohort study. Am J Obstet Gynecol 2004;190:644-653.
Related Letters:
Chronic Vulvovaginal Candidiasis
Kuebrich C. T., Retzer D. R., Sobel J. D., Eschenbach D. A.(David A. Eschenbach, M.D.)