Clinical Policy Title: Vaginitis diagnosis

Transcription

1 Clinical Policy Title: Vaginitis diagnosis Clinical Policy Number: Effective Date: September 1, 2017 Initial Review Date: July 20, 2017 Most Recent Review Date: September 21, 2017 Next Review Date: August 2018 Policy contains: Vaginitis Related policies: None. ABOUT THIS POLICY: AmeriHealth Caritas Northeast has developed clinical policies to assist with making coverage determinations. AmeriHealth Caritas Northeast s clinical policies are based on guidelines from established industry sources, such as the Centers for Medicare & Medicaid Services (CMS), state regulatory agencies, the American Medical Association (AMA), medical specialty professional societies, and peerreviewed professional literature. These clinical policies along with other sources, such as plan benefits and state and federal laws and regulatory requirements, including any state or plan specific definition of medically necessary, and the specific facts of the particular situation are considered by AmeriHealth Caritas Northeast when making coverage determinations. In the event of conflict between this clinical policy and plan benefits and/or state or federal laws and/or regulatory requirements, the plan benefits and/or state and federal laws and/or regulatory requirements shall control. AmeriHealth Caritas Northeast s clinical policies are for informational purposes only and not intended as medical advice or to direct treatment. Physicians and other health care providers are solely responsible for the treatment decisions for their patients. AmeriHealth Caritas Northeast s clinical policies are reflective of evidence based medicine at the time of review. As medical science evolves, AmeriHealth Caritas Northeast will update its clinical policies as necessary. AmeriHealth Caritas Northeast s clinical policies are not guarantees of payment. Coverage policy AmeriHealth Caritas Northeast considers vaginitis diagnosis by clinical evaluation and management (including laboratory services such as Gram stain, wet mount examination, herpes simplex virus culture, and syphilis IgG) to be clinically proven and, therefore, medically necessary. (Nwankwo 2017, Kriesel 2015, Sangkomkamhang 2015, van Schalkwyk 2015, Choe 2013, Lee 2012, Sherrard 2011) Limitations: AmeriHealth Caritas Northeast considers nucleic acid amplification (polymerase chain reaction [PCR]) for vaginitis diagnosis to be investigational, and therefore not medically necessary. AmeriHealth Caritas Northeast considers the routine screening for vaginitis in pregnant women at low risk for preterm delivery to be investigational, and therefore not medically necessary (U.S. Preventive Services Task Force 2008). 1

2 Alternative covered services: In network healthcare provider services for diagnosis and management of genital disorders. Background The American Congress of Obstetricians and Gynecologists (ACOG) maintains that vaginal symptoms are one of the most common presentations of patients to obstetrician gynecologists (ACOG 2006). Vaginitis may have significant penalties in terms of mental distress and physical discomfort, episodes of school or work absence, and sexual dysfunction. Vaginitis is frequently seen in concert with sexually transmitted diseases (STD), including human immunodeficiency virus (HIV). Diagnosis of vaginitis typically includes a suggestive history of perineal and vaginal discomfort, itching or discharge. Laboratory examination might include a microscopic examination of the discharge or vaginal vault with culture for bacterial, fungal and parasitic etiologies (e.g., candidiasis, trichomoniasis). Atrophic vaginitis (AV) is common with aging and the decreased ovarian production of estrogen. An accurate diagnosis of AV among postmenopausal women is vitally important to choosing the appropriate treatment. Searches AmeriHealth Caritas Northeast searched PubMed and the databases of: UK National Health Services Centre for Reviews and Dissemination. Agency for Healthcare Research and Quality s National Guideline Clearinghouse and other evidence based practice centers. The Centers for Medicare & Medicaid Services (CMS). We conducted searches on June 26, Search terms were: "vaginitis," "vaginal discharge," and "vaginal infection." We included: Systematic reviews, which pool results from multiple studies to achieve larger sample sizes and greater precision of effect estimation than in smaller primary studies. Systematic reviews use predetermined transparent methods to minimize bias, effectively treating the review as a scientific endeavor, and are thus rated highest in evidence grading hierarchies. Guidelines based on systematic reviews. Economic analyses, such as cost effectiveness, and benefit or utility studies (but not simple cost studies), reporting both costs and outcomes sometimes referred to as efficiency studies which also rank near the top of evidence hierarchies. 2

3 Findings A systematic review (Nwankwo 2017) of use of syndrome diagnosis in the evaluation of vaginitis followed the World Health Organization (WHO) algorithm and reported high sensitivity ( %) but moderate to low specificity (0 27.5%) among women with vaginal symptoms. The authors noted the method s substantial potential for overtreatment and physician error. A systematic review (n=4155 women) considered the notion that genital tract infection is associated with preterm birth (before 37 weeks' gestation) and whether screening for infections during pregnancy may reduce the numbers of babies being born prematurely (Sangkomkamhang 2015). The rate of preterm birth before 37 weeks' gestation was significantly lower in the intervention group (3% versus 5% in the control group) with a risk ratio (RR) of 0.55 (95% confidence interval (CI) 0.41 to 0.75; the evidence for this outcome was graded as of moderate quality). There is also evidence that routine screening of pregnant women before 20 weeks' gestation for vaginal infection is associated with cost savings when used for the prevention of preterm birth. The U.S. Preventive Services Task Force (USPSTF 2008, Nygren 2008) weighed the benefits versus harms of screening for bacterial vaginosis in pregnancy. The body recommended that clinicians should not screen for bacterial vaginosis in pregnant women at low risk for preterm delivery, and that current evidence is insufficient to assess the balance of benefits and harms of screening for bacterial vaginosis in pregnant women at high risk for preterm delivery. Numerous formulations for estrogen therapy are available, and the safety and efficacy of these preparations for the treatment of AV have been evaluated in randomized controlled clinical trials (Lynch 2009). Appropriate clinical intervention with vaginal estrogen formulations may safely offer postmenopausal women relief from undesirable symptoms and emotional distress associated with AV. Summary of clinical evidence: Nwankwo (2017) Syndromic Diagnosis in Evaluation of Women with Symptoms of Vaginitis. Systematic review of use of syndrome diagnosis in the evaluation of vaginitis Followed the WHO algorithm Reported high sensitivity ( %) but moderate to low specificity (0-27.5%) among women with vaginal symptoms. Studies in pregnancy reported sensitivity and specificity ranging from 35.4 to 54% for TV, 11 to 100% for bacterial vaginitis (BV), and 0 to 56.2% for trichomonas vaginalis, bacterial vaginosis, and vaginal candidiasis. Studies that added a point of care test reported higher sensitivity and specificity and positive predictive value. 3

4 Kriesel (2015) Multiplex PCR testing for nine different sexually transmitted infections. van Schalkwyk (2015) The authors concluded that the use of WHO syndrome-based algorithm or its modification for treatment of vaginitis though moderately effective has the potential for overtreatment and physician error. Point of care testing and laboratory investigation are essential for productive intervention especially in pregnancy. A research-use-only STI panel including multiple PCR primer sets for each organism was designed to detect Chlamydia trachomatis, Neisseria gonorrhoeae, Treponema pallidum, Trichomonas vaginalis, Mycoplasma genitalium, Ureaplasma urealyticum, Haemophilus ducreyi, and herpes simplex virus (HSV) types 1 and 2. Standard clinical testing included Gram stain, nucleic acid amplification, wet mount examination, herpes simplex virus culture, and syphilis IgG. Two hundred and ninety-five clinical specimens from 190 subjects were directly compared to standard testing. Urine (n = 146), urethral/cervical swabs (31), oral swabs (60), rectal swabs (43), and ulcer swabs (15) were tested. Among the tested samples, FilmArray detected C. trachomatis in 39 (13%), N. gonorrhoeae in 20 (7%), T. vaginalis in nine (3%), HSV 1 in five (2%), HSV 2 in five (2%), U. urealyticum in 36 (12%), M. genitalium in eight (3%), and T. pallidum in 11 (4%). Concordance between the FilmArray STI panel and standard nucleic acid amplification testing for C. trachomatis was 98% and for N. gonorrhoeae was 97%. Multiplex PCR STI testing has the potential to improve public health by providing rapid, sensitive, and reliable results within the clinic or nearby laboratory. Vulvovaginitis: screening for and management of trichomoniasis, vulvovaginal candidiasis, and bacterial vaginosis. Systematic review looked at the evidence for and provided recommendations on screening for and management of vulvovaginal candidiasis, trichomoniasis, and bacterial vaginosis. Vulvovaginal candidiasis affects 75% of women at least once. Topical and oral antifungal azole medications are equally effective. Following initial therapy, treatment success of recurrent vulvovaginal candidiasis (defined as 4 or more episodes per year) is enhanced by maintenance of weekly oral fluconazole for up to 6 months. Trichomonas vaginalis is best detected by antigen testing using vaginal swabs collected and evaluated by immunoassay or nucleic acid amplification test. Cure rates of up to 88% for trichomoniasis may be achieved with oral metronidazole 2 g once or 500 mg twice daily for 7 days. Partner treatment, even without screening, enhances cure rates. Test of cure following treatment of trichomoniasis with oral metronidazole is not recommended. Higher-dose therapy may be needed for treatment-resistant cases of trichomoniasis. In pregnancy, treatment of symptomatic Trichomonas vaginalis with oral metronidazole is warranted for the prevention of preterm birth. Bacterial vaginosis should be diagnosed using either clinical (Amsel's) or laboratory (Gram stain with objective scoring system) criteria. 4

5 Sangkomkamhang (2015) Antenatal lower genital tract infection screening and treatment programs for preventing preterm delivery. Kenyon (2014) Recent progress in understanding the epidemiology of bacterial vaginosis. Choe (2013) Performance of Anyplex II multiplex real-time PCR for the diagnosis of seven sexually transmitted infections: comparison with currently available methods. Symptomatic bacterial vaginosis should be treated with oral metronidazole 500 mg twice daily for 7 days. Alternatives include vaginal metronidazole gel and oral or vaginal clindamycin cream. Current evidence of the efficacy of alternative therapies for bacterial vaginosis (probiotics, vitamin C) is limited. Longer courses of therapy for bacterial vaginosis are recommended for women with documented multiple recurrences. Systematic review (n=4155 women) studied if genital tract infection is associated with preterm birth (before 37 weeks' gestation) and whether screening for infections during pregnancy may reduce the numbers of babies being born prematurely. The intervention group (2058 women) received infection screening and treatment for bacterial vaginosis, trichomonas vaginalis and candidiasis; the control group (2097 women) also received screening, but the results of the screening program were not revealed and women received routine antenatal care. The rate of preterm birth before 37 weeks' gestation was significantly lower in the intervention group (3% versus 5% in the control group) with a risk ratio (RR) of 0.55 (95% confidence interval (CI) 0.41 to 0.75; the evidence for this outcome was graded as of moderate quality). The incidence of preterm birth for infants with a weight equal to or below 2500 g (low birthweight) and infants with a weight equal to or below 1500 g (very low birthweight) were significantly lower in the intervention group than in the control group (RR 0.48, 95% CI 0.34 to 0.66 and RR 0.34; 95% CI 0.15 to 0.75, respectively; both graded as moderate quality evidence). Based on a subset of costs for preterm births of < 1900 g, the authors reported that for each of those preterm births averted, EUR 60,262 would be saved. Narrative review holds that the vaginal microbiome can be classified in five to eight clusters. Bacterial vaginosis-type clusters typically constitute one of these clusters, but in higher risk women, it can constitute up to three clusters. Biofilm-producing Gardnerella vaginalis are likely to play an important role in initiating the structured polymicrobial biofilm that is a hallmark of bacterial vaginosis. A narrative review notes that the real-time PCR assay is the most sensitive test for screening and diagnosing sexually transmitted infections (STIs) and has made diagnosing these infections easier for clinicians. The authors reported a series of a total of 897 specimens from 365 symptomatic patients and 532 asymptomatic volunteers were collected over a 10-month period. A total of 696 subjects provided 50ml of first-voided urine as samples, and 201 female patients provided endocervical swab specimens. Multiplex real-time PCR (Anyplex II) showed outstanding results in all fields, particularly sensitivity and specificity, compared with other diagnostic tools. 5

6 Lee (2012) Evaluation of Seeplex STD6 ACE Detection kit for the diagnosis of six bacterial sexually transmitted infections. Sherrard (2011) European (IUSTI/WHO) guideline on the management of vaginal discharge, Lynch (2009) Vaginal estrogen therapy for the treatment of atrophic vaginitis. Nygren (2008) This method yielded 100% sensitivity and high specificity for the detection of C. trachomatis, N. gonorrhoeae, T. vaginalis, M. genitalium, and M. hominis. It was also useful for discriminating between U. urealyticum and U. parvum. Traditional diagnosis of bacterial sexually transmitted infection (STI) has been dependent on the isolation of the causative pathogens by culturing endocervical or urethral swab specimens on selective media. Seeplex( ) STD6 ACE (auto-capillary electrophoresis) Detection assay employed six pairs of dual priming oligonucleotide (DPO ) primers specifically targeted to unique genes of Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, Ureaplasma urealyticum, Mycoplasma hominis, and Trichomonas vaginalis. A total of 739 specimens (304 cervical swabs and 435 urine samples) collected for 4 months were tested, and results were compared to those obtained with a combined monoplex PCR. The concordance between the multiplex PCR and monoplex PCR assay was 100% for both sensitivity and specificity. The authors concluded that multiplex PCR assay using the Seeplex( ) STD6 ACE Detection kit is a cost-effective and fast diagnostic tool with high sensitivity and specificity for the simultaneous detection of six STI pathogens. WHO guideline outlines the differential diagnoses of vaginitis and offers recommendations for treatment based on currently available evidence Narrative review notes that systemic administration of estrogen is effective in treating acute vasomotor symptoms typically associated with perimenopause and early menopause Standard doses may not be sufficient for the treatment of AV-related symptoms that generally arise after long-term estrogen deficiency. Vaginal estrogen preparations (e.g., creams, tablets, rings) are more often recommended for women with moderate to severe AV. Evidence on the benefits and harms of screening and treating pregnant women who are asymptomatic for bacterial vaginosis: an update review for the U.S. Preventive Services Task Force. The USPSTF has found no benefit to screening and treating women with low- or average-risk pregnancies for asymptomatic bacterial vaginosis. 6

7 U.S. Preventive Services Task Force.(2008) Screening for bacterial vaginosis in pregnancy to prevent preterm delivery: U.S. Preventive Services Task Force recommendation statement. ACOG Committee on Practice Bulletins Gynecology (2006) ACOG Practice Bulletin. Clinical management guidelines for obstetriciangynecologists, Number 72, May 2006: Vaginitis. The USPSTF weighed the benefits and harms of screening for bacterial vaginosis in pregnancy by identifying new evidence addressing previously identified gaps from the 2001 USPSTF recommendation. The body recommended that clinicians do not screen for bacterial vaginosis in pregnant women at low risk for preterm delivery, and that current evidence is insufficient to assess the balance of benefits and harms of screening for bacterial vaginosis in pregnant women at high risk for preterm delivery. Vaginal symptoms are common in the general population and are one of the most frequent reasons for patient visits to obstetrician-gynecologists. Vaginitis may have important consequences in terms of discomfort and pain, days lost from school or work, and sexual functioning and self-image. Vaginitis is associated with sexually transmitted diseases and other infections of the female genital tract, including human immunodeficiency virus (HIV), as well as adverse reproductive outcomes in pregnant and non-pregnant women. Treatment usually is directed to the specific cause of vaginal symptoms, which most commonly include bacterial vaginosis, vulvovaginal candidiasis, and trichomoniasis. References Professional society guidelines/other: ACOG Committee on Practice Bulletins Gynecology ACOG Practice Bulletin. Clinical management guidelines for obstetrician gynecologists, Number 72, May 2006: Vaginitis. Obstet Gynecol. 2006;107(5): U.S. Preventive Services Task Force. Screening for bacterial vaginosis in pregnancy to prevent preterm delivery: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2008;148(3): Peer reviewed references: Choe HS, Lee DS, Lee SJ, Hong SH, Park DC, Lee MK, Kim TH, Cho YH. Performance of Anyplex II multiplex real time PCR for the diagnosis of seven sexually transmitted infections: comparison with currently available methods. Int J Infect Dis. 2013;17(12):e Kenyon CR, Osbak K. Recent progress in understanding the epidemiology of bacterial vaginosis. Curr Opin Obstet Gynecol. 2014;26(6):

8 Kriesel J, Bhatia A, Barrus C, Vaughn M, Gardner J, Crisp RJ. Multiplex PCR testing for nine different sexually transmitted infections. Int J STD AIDS Dec;27(14): Lee SJ, Park DC, Lee DS, Choe HS, Cho YH. Evaluation of Seeplex STD6 ACE Detection kit for the diagnosis of six bacterial sexually transmitted infections. J Infect Chemother Aug;18(4): Lynch C. Vaginal estrogen therapy for the treatment of atrophic vaginitis. J Womens Health (Larchmt). 2009;18(10): Nwankwo TO, Aniebue UU, Umeh UA. Syndromic Diagnosis in Evaluation of Women with Symptoms of Vaginitis. Curr Infect Dis Rep. 2017;19(1):3. Nygren P, Fu R, Freeman M, Bougatsos C, Klebanoff M, Guise JM; U.S. Preventive Services Task Force. Evidence on the benefits and harms of screening and treating pregnant women who are asymptomatic for bacterial vaginosis: an update review for the U.S. Preventive Services Task Force. Ann Intern Med. 2008;148(3): Sangkomkamhang US, Lumbiganon P, Prasertcharoensuk W, Laopaiboon M. Antenatal lower genital tract infection screening and treatment programs for preventing preterm delivery. Cochrane Database Syst Rev. 2015;(2):CD Sherrard J, Donders G, White D, Jensen JS; European IUSTI. European (IUSTI/WHO) guideline on the management of vaginal discharge, Int J STD AIDS. 2011;22(8): van Schalkwyk J, Yudin MH. Vulvovaginitis: screening for and management of trichomoniasis, vulvovaginal candidiasis, and bacterial vaginosis. J Obstet Gynaecol Can. 2015;37(3): CMS National Coverage Determinations (NCDs): No NCDs were identified as of the writing of this policy. Local Coverage Determinations (LCDs): No LCDs were identified as of the writing of this policy. Commonly submitted codes Below are the most commonly submitted codes for the service(s)/item(s) subject to this policy. This is not an exhaustive list of codes. Providers are expected to consult the appropriate coding manuals and bill accordingly. 8

9 CPT Code Description Comments Amines, vaginal fluid, qualitative ph; body fluid, not otherwise specified Smear, primary source with interpretation; wet mount for infectious agents (e.g., saline, India ink, KOH preps) Infectious agent detection by nucleic acid (DNA or RNA); Candida species, direct probe technique Infectious agent detection by nucleic acid (DNA or RNA); Candida species, amplified probe technique Infectious agent detection by nucleic acid (DNA or RNA); Gardnerella vaginalis, direct probe technique Infectious agent detection by nucleic acid (DNA or RNA); Gardnerella vaginalis, amplified probe technique Infectious agent detection by nucleic acid (DNA or RNA); Trichomonas vaginalis, direct probe technique Infectious agent enzymatic activity other than virus (e.g., sialidase activity in vaginal fluid) ICD-10 Code Description Comments A59.01 Trichomonal vulvovaginitis B37.3 Candidiasis of vulva and vagina L29.2 Pruritus vulvae L29.3 Anogenital pruritus, unspecified O O23.93 Infection genitourinary tract, pregnancy HCPCS Level II Code N/A Description Comments 9