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Home , Clindamycin, Kraurosis vulvae, Salpingitis, Terconazole, Vulvitis

What’s Going on Down There? Denise Rizzolo, PhD, PA-C Introduction

• Vulvovaginitis is of the and vaginal tissues. • Characterized by and/or vulvar itching and irritation as well as possible vaginal odor. • Accounts for 10 million visits yearly in the US and is the most common gynecologic complaint in prepubertal girls. History- What should you ask?

• Pruritus -General or just one spot • Soreness: stinging / burning / pain • Difficulty with sex • Lumps • Discharge • Partner’s have any symptoms • History of similar symptoms Physical Examination

• Careful gynecologic exam • Inspection of discharge • Close examination of vulvovaginal area • Careful inspection of • Look at perineum as well Physiologic Discharge

• Responsible for 10 percent of cases of vaginal discharge. • Composed of vaginal squamous cells suspended in fluid medium. • Clinical characteristics: • clear to slightly cloudy • non-homogeneous • highly viscous • Changes throughout the month Normal Vaginal Discharge

• Not associated with: • itching • burning • malodor • Normal increase in volume • ovulation • following coitus • after menses • during pregnancy The Big 3

•Three most common causes of vulvovaginitis include: • • Vaginal • Trichomonas Vaginalis •Others include: atrophic , irritant vaginitis, and other STIs. Vaginal Candidiasis- Overview

• Less common in postmenopausal women, unless taking . • 90% of yeast are secondary to Candida Albican (Most common). • Risk Factors include: • Pregnancy • Oral contraceptives • Uncontrolled DM • Recent use • Discussing around tight underwear, cotton underwear, spandex • Literature has been mixed to support this theory. Vaginal Candidiasis- Signs and Symptoms

Patient Reports Physical Exam • The discharge varies from • Whitish cottage cheese watery to thick cottage cheese discharge discharge • Vulvar erythema and edema • Vaginal soreness • Vaginal erythema • • Severe vaginal itching • External dysuria Vaginal Candidiasis- Diagnosis

• Normal pH4-4.5 • Positive results on microscopic exam (yeast buds and pseudohyphae) • Culture if unsure Vaginal Candidiasis- Treatment

• The topically applied drugs are more effective than (CDC) • 2% cream (single dose bioadhesive product), 5 g intravaginally in a single application OR • 0.4% cream 5 g intravaginally daily for 7 days OR • Terconazole 0.8% cream 5 g intravaginally daily for 3 days OR • Terconazole 80 mg vaginal , one suppository daily for 3 days • Oral Agent: • 150 mg orally in a single dose Case:

• Beth is a 33-year-old single woman who has been in your practice for several years and left a message with your nurse that she has a pruritic vaginal discharge that has persisted for 2 weeks despite her attempts at using an over-the-counter yeast cream. Is it ever appropriate to treat without an examination? • Very frequently, women will attempt to self-diagnose their vaginitis and self-treat with any number of readily available topical or oral agents. • However, the accuracy of self-diagnosis is often worse than is widely assumed. • Given the non-specific nature of vulvovaginal symptoms, patients requesting treatment by telephone should be asked to come in for evaluation, particularly – as in this patient – if she has treated herself with a non-prescription without success.

** May also depend on the relationship with the patient How do you confirm the diagnosis of candidiasis? What is the treatment? • The diagnosis may be suggested on the basis of history and physical examination, but confirmation requires either • (1) visualization of branched and budding hyphae on KOH wet mount or • (2) a positive culture in a symptomatic woman. • Uncomplicated patients may be treated with either topical or oral fluconazole. • Occasionally, in more severe cases, a second dose or repeated doses of fluconazole will be required. CASE

28 year old housewife is seen by you for a one week history of a frothy, greenish, malodorous vaginal discharge. She also complains of dyspareunia and vaginal irritation. Vaginal pH is 6.5 What is the most likely diagnosis? a.Herpes genitalis b.Trichomonas vaginalis c. genitalium d.Bacterial vaginosis e. Trichomonas Vaginalis -Overview

• Almost always sexually transmitted. • In US, an estimated 3.7 million people have the . • However, only about 30% develop any symptoms of trichomoniasis. • Associated with adverse pregnancy outcomes. • T. vaginalis infection is associated with two- to threefold increased risk for HIV acquisition. Trichomonas Vaginalis -Signs and Symptoms

Patient Reports Physical Exam • Itching, burning, redness or • Classic strawberry cervix in only soreness of the genitals 2% of patients • Discomfort with urination • Diffuse erythema seen in 10- • A change in their vaginal 33% discharge (i.e., thin discharge or increased volume) that can be • Discharge will be noted clear, white, yellowish, or greenish) • *** Can have no symptoms at all Trichomonas Vaginalis -Diagnosis

• Vaginal pH greater than 4.5 • Flagella on saline microscopy • Nucleic acid amplification tests NAATs are the most sensitive tests for T.vaginalis and are now considered the gold standard for diagnosis (can use vaginal swab or urine) Trichomonas Vaginalis -Treatment

• Partners must be treated! • 2 g orally in a single dose OR • 2 g orally in a single dose • Alternative Regimen • Metronidazole 500 mg orally twice a day for 7 days Treatment Failure

• A common reason for treatment failure is reinfection. Therefore, it its critical to assure treatment of all sex partners at the same time.

• If treatment failure occurs with metronidazole 2 g orally in a single dose for all partners, treat with metronidazole 500 mg orally twice daily for 7 days or tinidazole 2 g orally single dose.

• If treatment failure of either of these regimens, consider retreatment with tinidazole or metronidazole 2 g orally once a day for 5 days.

• If repeated treatment failures occur, contact the Division of STD Prevention, CDC, for metronidazole-susceptibility testing (telephone: 404-718-4141, website: www.cdc.gov/std)

21 Case

•28 y/o female graduate student is seen for a 5- day history of a thin, greyish-white vaginal discharge associated with vaginal burning and a fishy odor. Whiff test: (+) . Vaginal pH: 5.5 What is the diagnosis? a.Bacterial vaginosis b.Candida vaginitis c.Trichomonas vaginitis d.Mixed infection e.Normal discharge Let’s Focus More on …. Bacterial Vaginosis What percent of women will return with a recurrent BV infection within 12 months after the initial infection? • 20% • 30% • 40% • 50% Bacterial Vaginosis - Overview

• Bacterial Vaginosis (BV), formally known as Gardnerella vaginitis, is a common dysbiosis affecting approximately 21 million women in the United States. • BV is often recurrent after treatment with 50% of women having return of symptoms within twelve months. • BV affects 29% of women overall and is more common in Black and Hispanic women with rates of 51% and 32%, respectively. Bacterial Vaginosis - Overview

• Some research suggests that it may precipitate preterm labor and has been associated with the development of Pelvic Inflammatory Disease (PID). • USPSTF- has recent EBM question posed on website regarding BV and Pre term labor ----will discuss more later.

• BV predisposes women to the acquisition of Sexually Transmitted Infections (STIs), including Human Virus (HIV). Bacterial Vaginosis - Pathophysiology

• In women with BV the native vaginal flora, hydrogen peroxide producing lactobacilli, that are responsible for maintaining an acidic environment, are replaced with invasive , G. vaginalis, species, and Mobiluncus species. • This promotes a basic pH that sets the environment for BV. • is capable of producing a biofilm that provides a matrix for other to cling to as well as making it harder for antibiotic therapy to penetrate and eradicate the infection. Bacterial Vaginosis – Risk Factors

• Increased incidence among women: • douche regularly, smoke tobacco , have an IUD in place and have sex with women. • Women that have sex with women have a higher rate of BV and usually both women are affected. • Recurrent BV is higher in women who have multiple sex partners and do not use . • Conversely those that use oral contraceptives such as the pill, have lower rates of BV. • Oral estrogen is thought to have a nurturing effect on the lactobacilli in the perhaps explaining the lower overall rate of BV in women that use oral contraceptives. Most women with BV present with symptoms? • True • False Bacterial Vaginosis – History and Physical Exam

• Most women with BV are asymptomatic and unaware they have BV. • Symptomatic women typically present with: • vaginal discharge • odor • sometimes irritation • It is not uncommon for women to report a previous episode of BV within the previous three months to a year. • Physical examination • thin milky discharge • at times a fishy odor is detectable • bimanual exam normal unless another STI is present Bacterial Vaginosis – Diagnosis

• Collection of vaginal discharge with a cotton tipped swab from the lateral and posterior vaginal walls for pH measurement and will demonstrate an alkaline environment greater than 4.5. • A saline wet mount slide made from the vaginal secretions will show clue cells. • A 10% potassium hydroxide solution (10% KOH) added to a slide of vaginal secretions will yield the fishy odor. Bacterial Vaginosis – Diagnosis

• Amsel’s criteria relies on the identification of 3 out of the 4 criteria being present, which include: • elevated pH above 4.5, measured with pH strips • thin homogenous discharge • fishy odor after application of 10% KOH solution to vaginal smear • 20% or greater clue cells on saline microscopy • This requires the clinician to be good at microbiology and vaginal exam. Bacterial Vaginosis – Diagnosis

• Nugent scoring and gram staining =gold standard for diagnosing BV. • Involves identifying and quantifying lactobacilli as well as G. vaginalis, Mobiluncus and species. • A numerical score is calculated by identifying how many lactobacilli or G. vaginalis/Bacteroides /Mobiluncus are in each field. • One bacteria or less per field is rated at +1 • Two to five bacterium is rated at +2 • Six to thirty bacterium is rated at +3 • Greater than 30 is rated +4. • A score of 0-3 is deemed normal, 4-6 is considered intermediate and 7-10 is indicative of BV. • This method is not practical for most office settings as it requires an onsite lab and the expertise to identify different bacterium. Bacterial Vaginosis – Diagnosis

• Affirm test - single swab collected from vagina for specimen (tests for Candida species, and Trichomonas vaginalis nucleic acid in vaginal fluid specimens from patients with symptoms of vaginitis/vaginosis.). • Results generated at lab. • This requires the clinician to place collection swab in tube and send to lab. What treatment would you offer this patient?

• • Amoxicillin • Ciprofloxin • Metronidazole Patient should abstain from sex during treatment? • True • False Bacterial Vaginosis- Treatment (General Guidelines) • Abstinence from sex during treatment for BV is preferred as condoms can be weakened by the use of vaginal creams and this effect may persist up to 5 days following treatment. • Symptomatic pregnant women are treated the same as those that are not pregnant. • Breastfeeding women can be treated safely with either oral or vaginal metronidazole. • Side effects are primarily gastrointestinal in nature, including and , metallic taste, should not be taken with alcohol. Bacterial Vaginosis- Treatment CDC Recommended Alternative Treatments Metronidazole 500mg by mouth twice a day x 7 days Metro 0.75% one applicator intra-vaginally every night for 5 nights vaginal 2% cream one applicator intra-vaginally every night for 7 nights CDC Recommended Alternative Treatments Tinidazole 2 grams by mouth for 2 days Tinidazole 1 gram by mouth for 5 days Clindamycin 300 milligrams by mouth twice a day for 7 days Clindamycin ovules 100 milligrams intra-vaginally each night for 3 nights Notes: Tinidazole use is not recommended in pregnant women. Pregnant or Breastfeeding women may use both oral and vaginal metronidazole safely. DOSE relapse after 4 wk

• Metronidazole 500 mg BID x 7 d 20 % • Metronidazole 2 g x 1 dose 50 % • Metronidazole vaginal gel 34 % • Clindamycin vaginal cream 42 % • Clindamycin vaginal ovules 49 % Is treating the partner recommended in cases of BV? • Yes • No Bacterial Vaginosis- Partner Treatment

• Despite some literature that suggests that BV may have the potential to be sexually transmitted, the CDC does not recommend treatment for male partners . • A systematic review conducted by Mehta did not find male partner treatment to be helpful in preventing recurrent BV. • A study by Bukusi, et al using a topical microbicide applied to male partner’s penis daily and before and after sex did not decrease the incidence of recurrent BV and actually increased it. • residual bactericidal effect of the microbicide persisting on the penis may have affected flora in the vagina during sexual intercourse which led to destruction of lactobacilli and overgrowth of BV pathogens. Bacterial Vaginosis- Recurrent Infection

• Table 2 CDC Suggested Extended Regimens for Frequent BV Recurrences • 0.75% Metronidazole gel Intravaginal twice weekly for 4-6 months, or • Metronidazole 500mg po bid x 7 days + intravaginal boric acid 600mg qd x 21 days then • 0.75% metronidazole gel twice weekly for 4-6 months, or • Metronidazole 2gms po q month + fluconazole 150mg q month Probiotics have been proven to be effective in the preventing of BV? • True • False Bacterial Vaginosis- Probiotics

• The use of probiotics is not currently recommended by the CDC for the treatment or prevention of BV. • Probiotics may be beneficial in re-colonizing vaginal flora and preventing recurrence of BV. • Few, if any adverse effects and thus it may be prudent to discuss them with patients who want a natural approach to balancing the vaginal environment. • No good quality studies recommend one formulation over another. Bacterial Vaginosis- Life Style Changes

• Stop douching can help reduce the recurrence of BV. • Smoking cessation should be recommended. • Limiting the number of sexual partners and consistent . • In patients using contraception, combined birth control pills can help reduce recurrence of BV. • There has been no reduction of recurrent BV by: • changing bathing practices • wearing certain underwear material • menstrual hygiene practices, such as using pads versus , has not impacted the incidence of recurrent BV. Which leads to ……

• https://www.uspreventiveservicestaskforce.org/Page/Document/draf t-research-plan/bacterial-vaginosis-in-pregnant-women-to-prevent- preterm-delivery-screening The 3 Lichens…..

• Lichen simplex • • The 3 Lichens

• All three cause similar skin change • The skin becomes thickened, pale, with increased skin markings [grooves]and fissures • L. Sclerosis can occur in early teen years • Can have an impact on sex life Lichen sclerosus- Overview

• Lichen sclerosus (LS) was described for the first time in 1887. • Since then, many synonyms have been in use, notably ‘,’ ‘vulvar dystrophy,’ ‘white spot disease,’ and ‘lichen sclerosus et atrophicus’ or ‘guttate scleroderma.’ • All of these terms have been abandoned and replaced by ‘lichen sclerosus.’ • Chronic, inflammatory skin disease with a distinct predilection for the anogenital region. • Exact prevalence of LS is difficult to ascertain and probably underestimated, since patients present to various clinical specialties. • Clinicians do not always recognize symptoms • patients may not report symptoms because of embarrassment or because they are asymptomatic when they see their healthcare provider Lichen sclerosus- Overview

• Considered an autoimmune diseases –more prevalent in female patients. • Chronic irritant effects of urinary contact are suggested to be provocative. • No infectious agent has been consistently linked to LS Lichen sclerosus- Natural Progression

• Scarring, chronic progressive or relapsing and remitting, lifelong condition. • minora may become reabsorbed and fused, and the entrapped under scar tissue. • Vaginal introitus may become stenotic and narrowed. • Less commonly, genital LS may be complicated by SCC. Lichen sclerosus- History and Physical Exam

• is the main symptom, often worse at night and sufficiently severe to disturb sleep. • Pain, soreness, and dysuria may be a consequence of erosions or fissures. • A high proportion of women reported that LS led to significant sexual problems including dyspareunia and apareunia due to continuing inflammatory disease as well as due to anatomic changes and scarring. • There are cases where LS is asymptomatic and noted on exam. Lichen sclerosus- History and Physical Exam

• Areas involved may vary from a small, single area to the entire region of vulva, perineum, and perianus. • May have extension to the genitocrural folds, buttocks, and thighs. • Characteristic sites involved are the interlabial sulci, and , clitoris and , and perineum and perianal area, giving rise to the characteristic ‘figure-of-eight’ shape. • Genital mucosal involvement does not occur, the vagina and cervix always being spared, in contrast to LP. • Tearing during sexual intercourse or physical examination is common. • Crinkling or cellophane paper-type appearance is pathognomonic. Lichen sclerosus- Diagnosis

• Usually clinical. • Clinically inconclusive cases, a histologic exam is advisable, but should never be interpreted in isolation. • A nonspecific biopsy does not rule out LS, but classic histologic findings confirm diagnosis. Lichen sclerosus- Treatment

• Minimize irritants, soap substitution, avoidance of urinary contact. • Moisturization with emollients. • Treatment of infections. Lichen sclerosus- Treatment

• Ultrapotent or potent topical corticosteroid (Clobetasol ): • once daily at night for 4 weeks, • then on alternate nights for 4 weeks, • and then twice weekly for a further 4 weeks. • Continued suppressive therapy according to the ongoing inflammatory activity • In corticosteroid-resistant cases, application of topical calcineurin inhibitors, topical in hyperkeratotic lesions, systemic retinoids, or photodynamic therapy • Surgery for intraepithelial neoplasia or carcinoma • Long-term surveillance Intralesional Corticosteriods

• Thickened lesions can be injected with • Inject directly into area – once per month for three months • Pre treatment with topical anesthetic can help with the pain and discomfort. • Response is high, but can be painful • Trial of topical steroids is recommended first Topical Calcineurin Inhibitors

• 2nd line therapy – check to make sure they were adhering to primary treatment first • Less potent then clobetasol • Apply twice daily, for three months- then re-evaluted • 0.1% vs Clobetasol 0.05% both applied daily for three months • Greater resolution found with Clobetasol • Adverse effects – long term safety is unknown. Other therapies

• Oral retinoids – Some resolution in thickened plaques – but high side effect profile (20-30 mg per day for 16 weeks) • UVA1 phototherapy • UVA 1 phototherapy 4 times a week was compared to clobetasol daily • Both had similar efficacy; however, quality of life improved with clobetasol • Topical and testosterone – studies limited and no significant findings- more research is needed. Lichen sclerosus- Follow up

• Patients under routine follow up will need a biopsy if: • (1) there is a suspicion of neoplastic change, persistent erosion, or erythema, or new warty or pustular lesions; • (2) there is an area resistant to adequate treatment; • (3) there is extragenital LS, with features suggesting an overlap with morphea; (4) there are pigmented areas, in order to exclude an abnormal melanocytic proliferation; • (5) second-line therapy is to be used. Prognosis

• Over age of 70 unlikely to have complete remission of symptoms • Relapses are common- 50 % relapse in 16 months and 84% relapse in within 4 years • For children- may see regression but potentially will continue into adulthood. Case

• A 57-year-old woman presents to clinic for a routine wellness exam. She reports bloating, gastrointestinal upset, and vaginal itching that has been going on for about 2 months, which she attributes to menopause and vaginal dryness. She has pain with intercourse, which has caused some strain with her husband. She is asking for vaginal lubricant. On exam you see as shown in the image. What symptoms for vaginal and vulvar cancers are present? (mark all that apply) • Persistent vaginal itching • Pain with intercourse • Bloating • GI upset What do you want to do next? (mark all that apply) • Refer the patient to gynecologist or gynecologic oncologist • Prescribe estrogen or cream • Tell her to return in one month if symptoms have not resolved • Biopsy the abnormal area if done in your practice Case

• A 64 y.o. G4P4 was recently diagnosed with lichen sclerosus (no biopsy performed). She was started on clobetasol propionate. She calls complaining of vulvar pain. Your diagnosis is?

• Lichen planus • Pemphigoid • Lichen planus with herpes • Invasive squamous cell carcinoma What percent of people with HSV-2 are unaware that they are infected? • 10-20% • 21 – 40% • 50- 70% • Over 80%

https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5915a3.htm Superinfections can occur!

• If there is a partial response to treatment – consider superinfection and obtain cultures • Can develop Staph, Strep, Herpes and even Candidiasis infections Next up….Lichen Planus Lichen Planus-Overview

• Autoimmune and less common • More painful • Just as destructive as LS • More likely to be seen on other parts of the patient • More difficult to treat than LS; may respond to immunosuppressive therapy Lichen planus: cutaneous type

• Violaceous plaques • Wickham’s striae • Labia majora • Irregular distribution Lichen planus: mucosal type

• May be very itchy • More often very painful • Very tender to touch • Destructive – loss of clitoral hood, labia minora • May cause introital narrowing • More likely to involve vagina (unlike lichen sclerosus (only vulva)) • May also affect oral mucosa • Buccal mucosa, inner lips, tongue • Desquamative gingivitis Erosive lichen planus

• Red glistening painful mucosal patch • Loss of labia minora Lichen Planus –Patient complaints

• Pruritus • Irritation • Rawness • Burning • Dyspareunia Lichen Planus -Diagnosis

• Biopsy Lichen Planus-Treatment

• Topical Clobetasol daily • May be required daily long-term • Topical calcineurin inhibitors, e.g., pimecrolimus cream • Oral prednisone • Methotrexate Finally Lichen Simplex Lichen Simplex- Overview

• Lichen simplex chronicus of the vulva is the end stage of the itch-scratch-itch cycle • The initial stimulus to itch may be: • Underlying seborrheic • Intertrigo • Tinea • • In most cases, the underlying cause is not evident and may have been transient or vaginal discharge. • Any itching disease of the vulva may become secondarily lichenified. • Remove the irritant and the skin recovers. Lichen Simplex- History and Physical Exam

• Hyperkeratotic, usually ill-defined, grayish, thickened, and sometimes excoriated lesion

• Usually located over the labia majora

• Hyperpigmentation

• Itching is always present and may be intense Lichen Simplex- Treatment

• Treatment • Includes removal of irritants and/or allergens • Topical application of mild-to-high–potency corticosteroids. • Avoid soaps and cleansing agents other than aqueous cream. • Discourage excessive cleaning of the genital area; use of hot water; overheating; and wearing of synthetic, rough, and/or tight clothing. • Lichen simplex chronicus may be associated with underlying diseases (eg, Paget disease, Bowen disease) • Thinning and of vaginal epithelium

• Most common in postmenopausal women with low estrogen levels

• Dyspareunia and vaginal spotting (differential includes uterine cancer)

• Treatment – vaginal or oral estrogen Contact Vulvovaginitis

• results from the exposure of vulvar epithelium and vaginal mucosa to a primary chemical irritant or an allergen. • perfumes, dyes, soaps, bubble baths, deodorants, tampons, pads, feminine hygiene products, topical , tight slack/pantyhose, synthetic underwear or scented toilet paper. • Clinically there may be local swelling, itching or burning sensation, ulcerations or even secondary infections. • Diagnosis is made by ruling out infectious causes and identifying the offending agent. Contact Vulvovaginitis

• Mild cases resolve spontaneously. • Treatment for more severe cases include: cool sitz baths, wet compresses of dilute boric acid or Burow’s solution, topical corticosteroids, and oral antihistamines. Chlamydia

• Chlamydia are obligate intracellular parasites, similar to gram (-) bacteria and inhibited by • Genital infections caused by C. trachomitis strains D through K • caused by strains L1, L2 or L3 • Chlamydial complications: • Acute , bartholinitis, proctitis, PID, conjunctivitis, Reiter’s syndrome, , perihepatitis (Fitz-Hught-Curtis syndrome), systemic complications such as arthritis, , Chlamydia - Epidemiology

• NGU peaked 1960s-1970s – stabilized in 1980s • In 2010 reported 1,307,893 cases • In 2011 reported 1,412,791 cases • In 2012 reported 1,422,976 cases • In 2014 reported 1,441,789 cases • In 2015 reported 1,526,658 cases • Believed to be under-reported, CDC estimates double reported • Largest burden among women <25 y/o Clinical Manifestations

• Asymptomatic infection is common • C. trachomatis causes 30-50% of NGU C. trachomatis urethritis generally less severe than gonococcal urethritis • Symptoms: • Vaginal discharge • Urethral discharge, dysuria, urethral itching • Minimal frequency/urgency and negative urine culture • >2/3 females with no symptoms Clinical Manifestations

• Known as ”silent” disease because the majority have no symptoms • If symptoms occur, usually appear 1-3 weeks after exposure Complications

• Females • Migrate into upper GU tract resulting in bartholinitis, salpingitis or perihepatitis, PID • Can cause chronic Diagnosis

• NAAT the most sensitive and FDA cleared to use with urine • Females: first catch urine, vaginal swab (provider or self collected) • Culture, however, expensive and not always available • Other test available but not typically used: • Direct immunofluorescence • Enzyme immunoassay • Antigen test • Nucleic acid hybridization • Many treated empirically Treatment

• Azithromycin 1 g PO single dose • OR • Doxycyline 100 mg PO BID x 7 days

• Treat all sexual contacts within 60 days • Test for other STIs • Abstinence from sex for 7 days after last partner has completed therapy and sx resolved • Test of cure is not recommended • Retest in 3 – 4 month for re-infection Treatment

• In pregnancy • Azithromycin 1g PO once • is contraindicated in pregnancy • Alternative available – see CDC • Test of cure in 3-4 wks after completion of Tx • Repeat testing in 3 month • Repeat test during 3rd trimester Gonorrhea • Gonorrhea is infection of columnar and transitional epithelium caused by • Neisseria gonorrhoeae is gram-negative usually found in pairs • Typically infects lower genital tract • Anatomic sites which can be infected directly: • urethra, rectum, conjunctiva, pharynx, and endocervix • Complications: • endometritis, salpingitis, , and bartholinitis in the females, and periurethral and epididymitis in males, also abscess and fistula formation, arthritis, dermatitis, , meningitis, myopericarditis, hepatitis, infertility Sexually Transmitted Infections Gonorrhea - Epidemiology • Incidence has steadily decreased since 1975 • 301,174 cases reported in 2009 - lowest since recording of gonorrhea rates began • 309,341 cases reported in 2010 • 321,849 cases reported in 2011 • 334,826 cases reported in 2012 • 333,004 cases reported in 2013 • 350,062 cases reported in 2014 • Young black women bear the heaviest burden Pathogenesis

• N. gonorrhoeae provokes an intense, suppurative inflammatory reaction • In females urethral and endocervical exudates tend to be less obvious • Acute inflammation of adjacent structures, such as Bartholin glands is common • Ascending infection may cause acute salpingitis, oopharitis, tubo- ovarian • Can cause scaring of structures and result in infertility Clinical Features

• In females: initial infection may be asymptomatic or associated with dysuria, lower pelvic pain, and vaginal discharge • Gonoccocal infection of the upper genital tract may spread to peritoneal cavity and result into perihepatitis • Resolution of inflammation results in the formation in “violin-string” adhesions between the dome of the and the adjacent diaphragm – Fitz-Hugh-Curtis syndrome • In homosexual men, primary infections more commonly are oropharynx and anorectal area, with resultant acute pharyngitis and proctatitis Clinical Features

• Disseminated infections 0.5% to 3% • More common in females than in males • Tenosynovitis, arthritis, pustular or hemorrhagic skin lesions, endocarditis, meningitis • Gonoccocal infections may be transmitted to infants during passage through the birth canal Diagnostics

• Nucleic acid amplification test (NAAT) allows the widest variety of specimen types and is FDA-cleared for use • Endocervial swab, vaginal swab, urethral swab (males only), urine (male and female) • Gram-stain urethral/cervical/rectal discharge • Intracellular gram-negative diplococci in leukocytes • Negative Gram stain is not sufficient for ruling out infection in asymptomatic males • Culture and sensitivity should be performed if suspected or documented treatment failure • Endocervical in females or urethral swab in males Diagnostics

• Gram stain of endocervical specimens, pharyngeal, or rectal specimens also are not sufficient to detect infection - not recommended. Treatment

• Patients infected with N. gonorrhoeae frequently are coinfected with C. trachomatis • Patients treated for gonococcal infection also must be treated routinely with a regimen that is effective against uncomplicated genital C. trachomatis infection • Increasing resistance Treatment

• Dual therapy • Uncomplicated infection of cervix, urethra, rectum: • Ceftriaxone 250 mg IM one dose • PLUS Azithromycin 1g PO once • Alternative regimens – see CDC Treatment

• GC of the pharynx more difficult to eradicate • Disseminated gonococcal infection • Hospitalization • Arthritis and arthritis-dermatitis • Ceftriaxone 1 g IM/IV q24h + Azithromycin 1g PO once • Switch to PO for total of minimum 7 days • Meningitis and endocarditis • Ceftriaxone 1-2 g IV q12-24h + Azithromycin 1g PO once • Meningitis parenteral tx x 10-14 days • Endocarditis parenteral tx x 4 wks Treatment

• Pregnant women infected with N. gonorrhoeae treated with dual therapy • Neonates can be infected during birth • Sexual abuse is the most frequent cause of gonococcal infection in infants and children Treatment

• Partners within 60 days treat empirically • Test for other STIs • Abstinence from sexual contact for 7 days after last partner has started antibiotic therapy and sx resolved • Test of cure is not recommended • Retest in 3 – 4 month for re-infection or at next encounter within 12 months Conclusion

• Many women will not discuss symptoms. • Most women present late, and very distressed. • They often feel guilt or ashamed. • They always feel embarrassed . • Discharge must be an STI. • Any lump most be a wart. References • 1. Amsel, R, Totten, PA, Spiegel, CA, Chen, KC, Eschenbach, D, Holmes, KK. Nonspecific vaginitis diagnostic criteria and microbial and epidemiological associations. Am J Med. 1983; 74: 14-22. • 2. Koumans, EH, Sternberg, M, Bruce, C, et al. The prevalence of bacterial vaginosis in the United States, 2001-2004; associations with symptoms, sexual behaviors, and reproductive health. Sex Transm Dis. 2007; 34(11): 864-869. • 3. Bradshaw, CS, Vodstrcil, LA, Hocking, JS, et al. Recurrence of bacterial vaginosis is significantly associated with post treatment sexual activities and hormonal contraceptive use. Clin Infect Dis. 2013; 56(6): 777-786. • 4. Taylor, BE, Darville, T, Haggerty, CL. Does bacterial vaginosis cause pelvic inflammatory disease? Sex Transm Dis. 2013; 40(2): 117-122. • 5. Sobel, R, Sobel, JD. Metronidazole for the treatment of vaginal infections. Expert Opin Pharmacother. 2015; 16(7): 1109-1115. • 6. Brotman, RM, Klebanoff, MA, Nansel, TR, et al. Bacterial vaginosis assessed by gram stain and diminished colonization resistance to incident gonococcal, chlamydial, and trichomonal genital infection. JID. 2010; 202(12): 1907-1915. • 7. Cohen, CR, Lingappa, JR, Baeten, JM, et al. Bacterial vaginosis associated with increased risk of female-to-male HIV-1 transmission: a prospective cohort analysis among African couples. PloS. 2012; 9(6): 1-9. • 8. Schwebke, JR, Muzny, CA, Josey, WE. Role of gardnerella vaginalis in the pathogenesis of bacterial vaginosis: a conceptual model. JID. 2014; 210(1): 338-342. • 9. Muzny, CA, Schwebke, JR. Pathogenesis of bacterial vaginosis: discussion of current hypotheses. JID. 2016; 214(1): 51-55. • 10. Zozaya, M, Ferris, MJ, Siren, JD, et al. Bacterial communities in penile skin, male urethra and of heterosexual couples with and without bacterial vaginosis. Microbiome. 2016; 4(16): 1- 10. • 11. Marrazzo, JM, Koutsky, LA, Eschenbach, DA, Agnew, K, Stine, K, Hiller, SL. Characterization of vaginal flora and bacterial vaginosis in women who have sex with women. JID. 2002; 185: 1307- 1313. • 12. Workowski, KA, Bolan, GA. MMWR sexually transmitted disease treatment guidelines 2015. MMWR. 2015; 64(RR3): 69-72. • 13. Sobel, JD. Vaginal Biofilm: much ado about nothing, or a new therapeutic challenge? Clin Infect Dis. 2015; 61: 607-608. • 14. Ankum, KC, Idemoh, C, Olise, N. Evaluation of bacterial vaginosis (bv) using nugent scoring system. JMBR. 2014; 13(1): 25-32. • 15. Mohammadzadeh, F, Dolatian, M, Jorjani, M, Majd, HA. Diagnostic value of amsel’s criteria for diagnosis of bacterial vaginosis. Glob J Health Sci. 2015; 7(3): 8-14. • 16. Myziuk, L, Romanowski, B, Johnson, SC. BV blue test for diagnosis of bacterial vaginosis. J Clin Microbiol. 2003; 41: 1925-1928. • 17. West, B, Morison, L, Van Der Loeff, MS, et al. Evaluation of a new rapid diagnostic kit FemExam for bacterial vaginosis in patients with vaginal discharge syndrome in the Gambia. Sex Transm Dis. 2003; 30 (6): 483-489. • 18. Crist, AE, Bankert, D, Mallory, RV, Rank, EL, Althouse, M. Comparison of the bd affirm vpIII test to primary care and clinical laboratory methods for the diagnosis of bacterial vaginosis and yeast vaginitis. Infect Dis Clin Pract. 2011; 19(4): 273-275. • 19. Tokyol, C, Aktepe, OC, Cerioglu, AS, Altindis, M, Dilek, FH. Bacterial vaginosis: comparison of pap smear and microbiological test results. Mod Pathol. 2004; 17: 857-860. • 20. Sheehy, O, Santos, F, Ferreira, E, Berard, A. The use of metronidazole during pregnancy: a review of evidence. Curr Drug Safe. 2015; 10: 170-179. References

• 21. Chung, AM, Reed, MD, Blumer, JL. Antibiotics and breast-feeding: a critical review of the literature. Pediatr Drugs. 2002; 4(12): 817-837. • 22. Cleocin Hydrochloride Capsules (clindamycin hydrochloride)-drug summary. Physicians’ Desk Reference Web site. http://www.pdr.net/drug-summary/Cleocin-Hydrochloride- Capsules-clindamycin-hydrochloride-1864 Published 2016. Accessed November 11, 2016. • 23. United States Preventative Services Task Force. Screening for bacterial vaginosis in pregnancy to prevent preterm delivery: U.S. preventative services task force recommendation statement. Ann Int Med. 2008; 148(3): 218. • 24. Ugwumadu, A, Manyonda, I, Reid, F, Hay, P. Effect of early oral clindamycin on late miscarriage and preterm delivery in asymptomatic women with abnormal vaginal flora and bacterial vaginosis: a randomized controlled trial. Lancet. 2003; 361: 983-988. • 25. Lamont, RF, Duncan, SLB, Mandau, D. Intravaginal clindamycin to reduce in women with abnormal genital tract flora. ACOG. 2003; 101(3): 516-522. • 26. Jorgensen, JS, Weile, LKK, Lamont, RF. The early use of appropriate prophylactic antibiotics in susceptible women for the prevention of preterm birth of infectious etiology. Expert Opin Pharmacother. 2014; 15(15): 2173-2191. • 27. Brocklehurst, P, Gordon, A, Milan, SJ. Antibiotics for treating bacterial vaginosis in pregnancy. Cochrane Database of Systematic Reviews 2013. Issue 1, Art. No. : CD000262. DOI: 10.1002/14651858.CD000262.pub4. • 28. Mehta, SD. Systematic review of randomized trials of treatment of male sexual partners for improved bacterial vaginosis outcomes in women. Sex Transm Dis. 2012; 39(10): 822-830. • 29. Bukusi, E, Thomas, KK, Nguti, R, et al. Topical penile microbicide use by men to prevent recurrent bacterial vaginosis in sex partners: a randomized . Sex Transm Dis. 2011; 38(6): 483-489. • 30. Forcey, DS, Vodstrcil, LA, Hocking, JS, et al. Factors associated with bacterial vaginosis among women who have sex with women: a systematic review. PloS. 2015; 10(12): 1- 15. • 31. Sobel, JD, Ferris, D, Schwebke, J, et al. Suppressive antibacterial therapy with 0.75% metronidazole vaginal gel to prevent recurrent bacterial vaginosis. Am J Obstet Gynecol. 2006; 194: 1283-1289. • 32. Reichman, O, Akins, R, Sobel, JD. Boric acid addition to suppressive antimicrobial therapy for recurrent bacterial vaginosis. Sex Transm Dis. 2009; 36(11): 732-734. • 33. Aguin, T, Akins, RA, Sobel, JD. High-dose maintenance metronidazole for recurrent bacterial vaginosis: a pilot study. Sex Transm Dis. 2014; 41(5): 290-291. References

• 34. Krasnopolsky, VN, Prilepskaya, VN, Polatti, F. Efficacy of tablets as prophylaxis for recurrent bacterial vaginosis: a randomized double-blind, placebo-controlled trial. J Clin Med Res. 2013; 5(4): 309-315. • 35. Larsson, PG, Brandsborg, E, Forsum, U, et al. Extended antimicrobial treatment of bacterial vaginosis combined with human lactobacilli to find the best treatment and minimize the risk of relapses. BMC Infect Dis. 2011; 11(223): 1-14. • 36. Weissenbacher, ER, Donders, G, Unzeitig, V, et al. A comparison of chloride vaginal tablets (Fluomizin) and clindamycin vaginal cream in the treatment of bacterial vaginosis: a single-based, randomized clinical trial of efficacy and safety. Gynecol Obstet Invest. 2013; 73: 8-15. • 37. Laghi, L, Picone, G, Cruciani, F, et al. modulates the vaginal microbiome and metabolome in women affected by bacterial vaginosis. Anitmicrob Agents and Chemother. 2014; 58(6): 3411-3420. • 38. Zhong-ming, Z, Qi-pin, L, Chen, Y, et al. Directed shift of vaginal flora after topical application of sucrose gel in a phase III clinical trial: a novel treatment for bacterial vaginosis. Chin Med J. 2010; 123(15): 2051-2057. • 39. Vujic, G, Knez, AJ, Stefanovic, VD, Vrbanovic, VK. Efficacy of orally applied probiotic capsules for bacterial vaginosis and other vaginal infections: a double-blind, randomized, placebo-controlled study. Eur J Obstet Gynecol Reprod Biol. 2013; 168: 75-79. • 40. Ya, W, Reifer, C, Miller, L. Efficacy of vaginal probiotic capsules for recurrent bacterial vaginosis: a double-blind, randomized, placebo-controlled study. Am J Obstet Gynec. 2010; 203: 120e1-120e6. • 41. Bodean, O, Munteanu, O, Cirstoiu, C, Secara, D, Cirstoiu, M. Probiotics- a helpful additional therapy for bacterial vaginosis. J Med Life. 2013; 6(4): 434-436. • 42. Marcone, V, Calzolari, E, Bertini, M. Effectiveness of vaginal administration of Lactobacillus rhamnosus following conventional metronidazole therapy: how to lower the rate of bacterial vaginosis recurrences. New Microbiol. 2008; 31: 429-433. • 43. Laxmi, U, Agrawal, S, Raghunandan, C, Randhawa, VS, Saili, A. Association of bacterial vaginosis with adverse fetomaternal outcome in women with spontaneous preterm labor: a prospective cohort study. J Matern Fetal Neonatal Med.2012; 25(1): 64-67. • 44. Gillet, E, Meys, JFA, Verstraelen, H, et al. Bacterial vaginosis is associated with uterine cervical human papillomavirus infection: a meta-analysis. BMC Infect Dis. 2011; 11(10): 1-9. • 45. Gao, W, Weng, J, Gao, Y, Chen, X. Comparison of the vaginal microbiota diversity of women with and without human papillomavirus infection: a cross-sectional study. BMC Infect Dis. 2013; 13(271): 1-10. • 46. Bilardi, J, Walker, S, McNair, R, et al. Women’s management of recurrent bacterial vaginosis and experiences of clinical care: a qualitative study. PloS. 2016; 11(3):1-.doi:10.1371/journal.pone.0151794. • 47. Klebanoff, MA, Nansel, TR, Brotman, RM, et al. Personal Hygienic behaviors and bacterial vaginosis. Sex Transm Dis. 2010; 37(2): 94-99. • 48. Brotman, RM, He, X, Gajer, P, et al. Association between cigarette smoking and the vaginal microbiota: a pilot study. BMC Infect Dis. 2014; 14(471): 1-11. • 49. Klatt, TE, Cole, DC, Eastwood, DC, Barnabei, VM. Factors associated with recurrent bacterial vaginosis. J Reprod Med. 2010; 55(1-2): 55-61.