Lower genital tract infections

Ina S. Irabon, MD, FPOGS, FPSRM, FPSGE Obstetrics and Gynecology Reproductive Endocrinology and Infertility Laparoscopy and Hysteroscopy To download lecture deck Main Reference

´Comprehensive Gynecology 7th edition, 2017 (Lobo RA, Gershenson DM, Lentz GM, Valea FA editors); chapter 23, Genital tract infections Outline

´ Infections of the ´ Infections of the vagina ´ Infections of the cervix Infections of the vulva 23 Genital Tract Infections Vulva, Vagina, Cervix, Toxic Shock Syndrome, Endometritis, and Salpingitis Carolyn Gardella, Linda O. Eckert, Gretchen M. Lentz

For clarity of presentation, discussion of infectious diseases of secondary bacterial, viral, parasitic, or fungal infections and is sensi- the female genital tract is divided into those of the lower geni- tive to hormonal and allergic infuences. Vulvar pruritus accounts tal tract, the vulva, vagina, and cervix; and those of the upper for approximately 10% of outpatient gynecology visits. Vulvar - genital tract, the endometrium and fallopian tubes. However, ing or burning of acute onset and short duration suggests infection the female genital tract has anatomic and physiologic continuity, or contact dermatitis. Skin fssures and excoriation may be signs of so infectious agents that colonize and involve one organ often infection, may be caused by the woman’s scratching as a result of infect adjacent organs. To understand the pathophysiology and irritation from a vaginal discharge, or may be the manifestation of natural history of infectious diseases of the genital tract, one a primary dermatologic disease. Box 23.1 presents the diferential must keep this continuity in mind. diagnosis of vulvar pruritus and irritation (Prabhu, 2015). Te symptoms caused by infections of the lower genital tract produce the most common conditions seen by gynecologists. Terefore the initial focus of this chapter is on clinical presenta- Box 23.1 Causes of Vulvar Pruritus and Irritation tion and the diferential diagnosis of vulvitis, vaginitis, and cer- Acute: vicitis. Contact Dermatitis Toxic shock syndrome (TSS) and are also discussed in Allergic this chapter. Although the most devastating pathologic processes Irritant from these diseases occur in sites other than the genital tract, they often obtain entry into the body through the vulvar, rectal, Infections vaginal, or cervical epithelium. Candidiasis Many of the infections discussed in this chapter may be papilloma acquired through sexual contact and are termed sexually transmit- ted infections (STIs). STIs often coexist—for example, trachomatis and . When one disease is sus- pected, appropriate diagnostic methods must be used to detect Chronic: other infections. Contact Dermatitis Te Centers for DiseaseCause Control and Preventionof (CDC) regu- Allergic larly revises management protocols for STIs. Recommendations and Irritant medications in this edition are based on the 2015 CDC guidelines. Vulvar Dystrophies Readers are urged to consultvulvar updates in thepruritus online CDC guidelines Lichen planus (http://www.cdc.gov) because bacterial sensitivities and epidemio- Lichen sclerosis logic concerns may lead to changes in treatment protocols. Lichen simplex chronicus and irritation Psoriasis Infections INFECTIONS OF THE VULVA Candidiasis Human papillomavirus Te skin of the vulva is composed of a stratifed squamous epithe- Neoplasia lium containing follicles and sebaceous, sweat, and apocrine Paget disease glands. Te subcutaneous tissue of the vulva also contains spe- cialized structures such as the Bartholin glands. Similar to skin Atrophy elsewhere on the body, the vulvar area is subject to primary and

Comprehensive Gynecology 7th edition, 2017 (Lobo RA, Gershenson DM, Lentz GM, Valea FA editors); 524 chapter 23, Genital tract infections

Obstetrics & Gynecology Books Full INFECTIONS OF BARTHOLIN GLANDS

´ Bartholin glands are two rounded, pea-sized glands deep in the perineum that are not palpable unless enlarged. ´ Bartholin glands are located at the entrance of the vagina at 5 and 7 o’clock, in the groove between the hymen and the labia minora. ´ Mucinous secretions from Bartholin glands provide moisture for the epithelium of the vestibule. ´ The most common cause of Bartholin gland enlargement is cystic dilation of the Bartholin duct à typically caused by distal obstruction secondary to non-specific or trauma. ´ differential diagnosis: mesonephric cysts of the vagina and epithelial inclusion cysts. ´ Mesonephric cysts are generally more anterior and cephalad in the vagina ´ Epithelial inclusion cysts are more superficial.

Comprehensive Gynecology 7th edition, 2017 (Lobo RA, Gershenson DM, Lentz GM, Valea FA editors); chapter 23, Genital tract infections INFECTIONS OF BARTHOLIN GLANDS

´ The cysts may vary from 1 to 8 cm in diameter and are usually unilateral, tense, and nonpainful. ´ abscess of a Bartholin gland tends to develop rapidly over 2 to 4 days presenting with difficulty in ambulation and sitting. ´Acute pain and tenderness can be severe, secondary to enlargement, hemorrhage, or secondary infection. ´signs : erythema, acute tenderness, edema and, occasionally, cellulitis ´Positive cultures from Bartholin gland abscesses are often polymicrobial and contain a wide range of similar to the normal flora of the vagina.

Comprehensive Gynecology 7th edition, 2017 (Lobo RA, Gershenson DM, Lentz GM, Valea FA editors); chapter 23, Genital tract infections INFECTIONS OF BARTHOLIN GLANDS

´ Asymptomatic cysts in women younger than 40 years do not need treatment. ´ Simple incision and drainage of a Bartholin gland cyst or abscess is not recommended because recurrence after incision and drainage is frequent. ´ The surgical treatment of choice is marsupialization to develop a fistulous tract from the dilated duct to the vestibule. ´ An elliptical wedge of tissue is excised over the cyst just proximal to the hymenal ring. ´ A cruciate incision is made into the cyst wall, and the edges of the duct or abscess are everted and sutured to the surrounding skin with interrupted absorbable sutures forming an epithelialized pouch that provides ongoing drainage for the gland.

Comprehensive Gynecology 7th edition, 2017 (Lobo RA, Gershenson DM, Lentz GM, Valea FA editors); chapter 23, Genital tract infections 23 Genital Tract Infections 525

INFECTIONS OF BARTHOLIN GLANDS abscesses tend to rupture spontaneously by the third or fourth Bartholin glands are two rounded, pea-sized glands deep in the day. Unilateral or bilateral Bartholin gland infection in most perineum that are not palpable unless enlarged. Tey drain via cases is not caused by a sexually transmitted infection. Positive ducts approximately 2 cm long lined by transitional epithelium cultures from Bartholin gland abscesses are often polymicrobial and located at the entrance of the vagina at 5 and 7 o’clock, and contain a wide range of bacteria similar to the normal fora in the groove between the hymen and the labia minora. Muci- of the vagina. nous secretions from Bartholin glands provide moisture for the Te treatment of enlargement or infection of Bartholin epithelium of the vestibule. Approximately 2% of adult women glands depends on symptomatology. Asymptomatic cysts in develop enlargements of one or both glands. Te most common women younger than 40 years do not need treatment. Simple cause is cystic dilation of the Bartholin duct (Fig. 23.1), typically incision and drainage of a Bartholin gland cyst or abscess is not caused by distal obstruction secondary to non-specifc infam- recommended because recurrence after incision and drainage is mation or trauma. Following obstruction, there is continued frequent. Instead, the surgical treatment of choice is marsupi- secretion of glandular fuid, which results in the cystic dilation. alization to develop a fstulous tract from the dilated duct to Te diferential diagnosis of vulvar cysts also includes meso- the vestibule. An elliptical wedge of tissue is excised over the nephric cysts of the vagina and epithelial inclusion cysts. Meso- cyst just proximal to the hymenal ring. A cruciate incision is nephric cysts are generally more anterior and cephalad in the made into the cyst wall, and the edges of the duct or abscess are vagina, whereas epithelial inclusion cysts are more superfcial. everted and sutured to the surrounding skin with interrupted Rarely, a lipoma, fbroma, hernia, vulvar varicosity, or hydrocele absorbable sutures forming an epithelialized pouch that provides may be confused with a Bartholin duct cyst. ongoing drainage for the gland. Te recurrence rate following Most women with Bartholin duct cysts are asymptomatic. marsupialization is approximately 5% to 10%. An alternative Te cysts may vary from 1 to 8 cm in diameter and are usu- surgical approach is to insert a Word catheter, a short catheter ally unilateral, tense, and nonpainful. Most cysts are unilocu- with an infatable Foley balloon, through a stab incision into the lar. However, in chronic or recurrent cysts there occasionally are abscess and leave it in place for 4 to 6 weeks (Fig. 23.2). During multiple compartments. this period, a tract of epithelium will form. All the procedures In contrast, an abscess of a Bartholin gland tends to develop mentioned may be performed with local anesthesia. Antibiotics rapidly over 2 to 4 days with signifcant symptoms, includ- are not necessary unless there is an associated cellulitis surround- ing difculty in ambulation. Acute pain and tenderness can be ing the Bartholin gland abscess. severe and are secondary to rapid enlargement, hemorrhage, Women older than 40 years with gland enlargement require a or secondary infection. Te signs are those of a classic abscess: biopsy to exclude adenocarcinoma of the Bartholin gland. Exci- erythema, acute tenderness, edema and, occasionally, cellulitis sion of a Bartholin duct and gland is indicated for persistent deep of the surrounding subcutaneous tissue. Without therapy, most infection, multiple recurrences of abscesses, or recurrent enlarge- ment of the gland in women older than 40 years. Excision can be challenging because of the rich vascular supply to the region and may be accompanied by morbidity, including intraopera- tive hemorrhage, hematoma formation, fenestration of the labia, INFECTIONS OF BARTHOLIN GLANDSpostoperative scarring, and associated dyspareunia. It is best to use regional block or general anesthesia for excision. Excision of ´ An alternative surgical approach is to insert a Word a Bartholin gland for recurrent infection should be performed catheter, a short catheter with an inflatable Foley when the infection is quiescent (Heller, 2014; Kessous, 2013; Khanna, 2010; Li, 2011; Wechter, 2009). balloon, through a stab incision into the abscess and leave it in place for 4 to 6 weeks ´ Women older than 40 years with gland enlargement require a biopsy to exclude adenocarcinoma of the Bartholin gland. ´ Excision of a Bartholin duct and gland is indicated for persistent deep infection, multiple recurrences of abscesses, or recurrent enlargement of the gland in women older than 40 years. Figure 23.1 Bartholin abscess. The mass is tender and fluctuant and is situated on the lower lateral aspect of labium minus at Figure 23.2 Word catheters before and afer inflation. They are 5 o’clock. (From Kaufman RH. Cystic tumors. In: Kaufman RH, used to develop a fistula from a Bartholin cyst or abscess to the Faro S, eds. Benign Diseases of the Vulva and Vagina. 4th ed. St. Louis: vestibule. (From Friedrich EG. Vulvar Disease. 2nd ed. Philadelphia: Mosby–Year Book; 1994.) WB Saunders; 1983.)

Obstetrics & Gynecology Books Full Comprehensive Gynecology 7th edition, 2017 PUBIS

´ the skin of the vulva is a frequent site of by parasites, the two most common being the and the itch mite. ´ is an infestation by the crab louse, Phthirus pubis. ´ the crab louse is also called the pubic louse and is a different species from the body or . ´ Lice in the are the most contagious of all STIs, with over 90% of sexual partners becoming infected following a single exposure.

th ´ The louse’s life cycle has three stages: Comprehensive Gynecology 7 edition, 2017 egg (nit), nymph, and adult. The entire life cycle is spent on the host. PEDICULOSIS PUBIS

´ The predominant clinical symptom of louse infestation is constant pubic pruritus caused by allergic sensitization. ´ Examination of the vulvar area without magnification demonstrates eggs and adult lice and pepper grain feces adjacent to the hair shafts ´ For definitive diagnosis, one can make a microscopic slide by scratching the skin papule with a needle and placing the crust under a drop of mineral oil.

Comprehensive Gynecology 7th edition, 2017 (Lobo RA, Gershenson DM, Lentz GM, Valea FA editors); chapter 23, Genital tract infections 23 Genital Tract Infections 527

12 hours and washed of, or ivermectin, 250 µg/kg, repeated in recommended for pubic lice with the 5% cream 2 weeks. None of these should be applied to the eyelids. Retreat- recommended for scabies (Leone, 2007; Scott, 2011). ment may be necessary if lice are found or if eggs are observed at the hair-skin junction. Patients with pediculosis pubis should be MOLLUSCUM CONTAGIOSUM evaluated for other STIs and evaluated after 1 week if symptoms persist. Tose who do not respond to one of the recommended Molluscum contagiosum is a poxvirus that replicates in the cyto- regimens should be retreated with an alternative regimen. plasm of cells and causes a chronic localized infection consist- To treat scabies, CDC recommends permethrin cream ing of fesh-colored, dome-shaped papules with an umbilicated applied to all areas of the body from the neck down and washed center. Like many in the pox family, molluscum is spread of after 8 to 14 hours or ivermectin, 200 µg/kg orally, repeated by direct skin-to-skin contact. However, lesions can be spread in 2 weeks, if necessary. Alternative regimens include , by autoinoculation, during contact sports, or by fomites on 1%, 1 oz of lotion or 30 g of cream applied thinly to all areas of bath sponges or towels. Te incubation period is 2 to 7 weeks. the body from the neck down and thoroughly washed of after In adults, it is primarily an asymptomatic disease of the vulvar 8 hours. Resistance to lindane has been reported in some parts skin, and, unlike most STIs, it is only mildly contagious. Wide- of the United States. Lindane is not recommended as frst-line spread infection in adults is most closely related to underlying therapy because of toxicity. It should only be used as an alterna- cellular immunodefciency, such as during an HIV infection. It tive if the woman cannot tolerate other therapies or if they have can also occur in the setting of chemotherapy or corticosteroid failed. Lindane should not be used immediately after a bath or administration. shower and should not be used by persons who have extensive Diagnosis is made by the characteristic appearance of the dermatitis, women who are pregnant or lactating, or children lesions. Te small nodules or domed papules of molluscum con- younger than 2 years. Patients with scabies have intense pruri- tagiosum are usually 1 to 5 mm in diameter (Fig. 23.6). Close tus that may persist for many days following efective therapy. inspection reveals that many of the more mature nodules have An antihistamine will help alleviate this symptom. Similar to an umbilicated center. An infected woman will typically have 1 pediculosis pubis, women should be examined 1 week following to 20 solitary lesions randomly distributed over the vulvar skin. initial therapy and retreated with an alternative regimen if live A crop of new nodules will persist from several months to years. mites are observed (Hu, 2008). If the diagnosis cannot be made by simple inspection, the white To avoid reinfection by pediculosis pubis or scabies, treat- waxy material from inside the nodule should be expressed on a ment should be prescribed for sexual contacts within the pre- microscopic slide. Te fnding of intracytoplasmic molluscum vious 6 weeks and other close household contacts. Tose with bodies with Wright or Giemsa stain confrms the diagnosis. close physical contact should be treated at the same time as the Te major complication of molluscum contagiosum is bacterial infected woman, regardless of whether they have symptoms. superinfection. Te umbilicated papules may resemble furuncles Bedding and clothing should be decontaminated (i.e., machine when secondarily infected. washed, machine dried using the heat cycle, or dry cleaned) or Molluscum contagiosum is usually a self-limiting infection removed from body contact for at least 72 hours. Fumigation of and spontaneously resolves after a few months in immunocom- living areas is not necessary. Importantly, women and physicians petent individuals. However, treatment of individual papules should not confuse the 1% cream rinse of permethrin dosage will decrease sexual transmission and autoinoculation of the SCABIES virus. After injection of local anesthesia, the caseous material is

´ Scabies is a parasitic infection of the itch mite, . ´ transmitted by close contact; Unlike louse infestation, scabies is an infection that is widespread over the body, without a predilection for hairy areas. ´ the adult female itch mite digs a burrow just beneath the skin à pathognomonic sign Figure 23.5 Skin scrapings of unexcoriated papules fortuitously disclose adults, larvae, eggs, and fecal pellets, any of which would Figure 23.6 Papule of molluscum contagiosum with umbilicated be diagnostic of scabies. (From Orkin M, Howard IM. Scabies. In: center. (From Brown ST. Molluscum contagiosum. In Holmes KK, Holmes KK, Mårdh PA, Sparling PF, et al, eds. Sexually Transmitted Mårdh PA, Sparling PF, et al, eds. Sexually Transmitted Diseases. ´ the predominant clinical symptom of scabies is severe Diseases. New York: McGraw-Hill; 1984.) New York: McGraw-Hill; 1984.) but intermittent itching à more intense pruritus occurs

at night when the skin is warmer and the mites are Obstetrics & Gynecology Books Full more active. ´ Scabies has been termed the great dermatologic imitator, and the differential diagnosis includes almost all dermatologic diseases that cause pruritus.

Comprehensive Gynecology 7th edition, 2017 (Lobo RA, Gershenson DM, Lentz GM, Valea FA editors); chapter 23, Genital tract infections SCABIES

´ therapy currently recommended is permethrin, 1% cream rinse, applied to affected areas and washed o after 10 minutes, or pyrethrins, with piperonyl butoxide applied to the affected area and washed off after 10 minutes. ´ An antihistamine will help alleviate pruritus. ´ To avoid reinfection by pediculosis pubis or scabies, treatment should be prescribed for sexual contacts within the previous 6 weeks and other close household contacts. ´ Bedding and clothing should be decontaminated (i.e., machine washed, machine dried using the heat cycle, or dry cleaned) or removed from body contact for at least 72 hours.

Comprehensive Gynecology 7th edition, 2017 (Lobo RA, Gershenson DM, Lentz GM, Valea FA editors); chapter 23, Genital tract infections 23 Genital Tract Infections 527

12 hours and washed of, or ivermectin, 250 µg/kg, repeated in recommended for pubic lice with the 5% permethrin cream 2 weeks. None of these should be applied to the eyelids. Retreat- recommended for scabies (Leone, 2007; Scott, 2011). ment may be necessary if lice are found or if eggs are observed at the hair-skin junction. Patients with pediculosis pubis should be MOLLUSCUM CONTAGIOSUM evaluated for other STIs and evaluated after 1 week if symptoms persist. Tose who do not respond to one of the recommended Molluscum contagiosum is a poxvirus that replicates in the cyto- regimens should be retreated with an alternative regimen. plasm of cells and causes a chronic localized infection consist- To treat scabies, CDC recommends permethrin cream ing of fesh-colored, dome-shaped papules with an umbilicated applied to all areas of the body from the neck down and washed center. Like many viruses in the pox family, molluscum is spread of after 8 to 14 hours or ivermectin, 200 µg/kg orally, repeated by direct skin-to-skin contact. However, lesions can be spread in 2 weeks, if necessary. Alternative regimens include lindane, by autoinoculation, during contact sports, or by fomites on 1%, 1 oz of lotion or 30 g of cream applied thinly to all areas of bath sponges or towels. Te incubation period is 2 to 7 weeks. the body from the neck down and thoroughly washed of after In adults, it is primarily an asymptomatic disease of the vulvar 8 hours. Resistance to lindane has been reported in some parts skin, and, unlike most STIs, it is only mildly contagious. Wide- of the United States. Lindane is not recommended as frst-line spread infection in adults is most closely related to underlying therapy because of toxicity. It should only be used as an alterna- cellular immunodefciency, such as during an HIV infection. It tive if the woman cannot tolerate other therapies or if they have can also occur in the setting of chemotherapy or corticosteroid failed. Lindane should not be used immediately after a bath or administration. shower and should not be used by persons who have extensive Diagnosis is made by the characteristic appearance of the dermatitis, women who are pregnant or lactating, or children lesions. Te small nodules or domed papules of molluscum con- younger than 2 years. Patients with scabies have intense pruri- tagiosum are usually 1 to 5 mm in diameter (Fig. 23.6). Close tus that may persist for many days following efective therapy. inspection reveals that many of the more mature nodules have An antihistamine will help alleviate this symptom. Similar to an umbilicated center. An infected woman will typically have 1 pediculosis pubis, women should be examined 1 week following to 20 solitary lesions randomly distributed over the vulvar skin. initial therapy and retreated with an alternative regimen if live A crop of new nodules will persist from several months to years. mites are observed (Hu, 2008). If the diagnosis cannot be made by simple inspection, the white To avoid reinfection by pediculosis pubis or scabies, treat- waxy material from inside the nodule should be expressed on a ment should be prescribed for sexual contacts within the pre- microscopic slide. Te fnding of intracytoplasmic molluscum vious 6 weeks and other close household contacts. Tose with bodies with Wright or Giemsa stain confrms the diagnosis. close physical contact should be treated at the same time as the Te major complication of molluscum contagiosum is bacterial infected woman, regardless of whether they have symptoms. superinfection. Te umbilicated papules may resemble furuncles Bedding and clothing should be decontaminated (i.e., machine when secondarily infected. washed, machine dried using the heat cycle, or dry cleaned) or Molluscum contagiosum is usually a self-limiting infection removed from body contact for at least 72 hours. Fumigation of and spontaneously resolves after a few months in immunocom- MOLLUSCUM CONTAGIOSUMliving areas is not necessary. Importantly, women and physicians petent individuals. However, treatment of individual papules should not confuse the 1% cream rinse of permethrin dosage will decrease sexual transmission and autoinoculation of the virus. After injection of local anesthesia, the caseous material is ´ chronic localized infection consisting of flesh-colored, dome-shaped papules with an umbilicated center. ´ molluscum is spread by direct skin-to-skin contact. ´ it is primarily an asymptomatic disease of the vulvar skin, and, unlike most STIs, it is only mildly contagious. ´ Widespread infection in adults is most closely related to underlying cellular immunodeficiency, such as during an HIV infection, chemotherapy or corticosteroid administration. ´ To confirm diagnosis à white waxy material from inside the nodule may be expressed on a microscopic slide à Figure 23.5 Skin scrapings of unexcoriated papules fortuitously intracytoplasmic molluscumdisclose bodies adults, larvae, with eggs, Wright and fecal pellets, or any Giemsa of which would Figure 23.6 Papule of molluscum contagiosum with umbilicated stain confirms the diagnosis.be diagnostic of scabies. (From Orkin M, Howard IM. Scabies. In: center. (From Brown ST. Molluscum contagiosum. In Holmes KK, Holmes KK, Mårdh PA, Sparling PF, et al, eds. Sexually Transmitted Mårdh PA, Sparling PF, et al, eds. Sexually Transmitted Diseases. ´ the major complication of molluscumDiseases. New York: McGraw-Hill; contagiosum 1984.) is New York: McGraw-Hill; 1984.) bacterial superinfection

´ Molluscum contagiosum is usually a self-limiting infectionObstetrics & Gynecology Books Full and spontaneously resolves after a few months in immunocompetent individuals

Comprehensive Gynecology 7th edition, 2017 528 Part III GENERAL GYNECOLOGY

evacuated and the nodule excised with a sharp dermal curette. Tere are two distinct types of HSV, type 1 (HSV-1) and Te base of the papule is chemically treated with ferric subsulfate type 2 (HSV-2). In the past, a broad generalization was that (Monsel solution) or 85% trichloroacetic acid. Alternative meth- HSV-1 tends to infect epithelium above the waist, and HSV-2 ods are cantharidin, a chemical blistering agent, imiquimod, or tends to cause ulceration below the waist. However, HSV-1 is cryotherapy (Al-Mutairi, 2010; Chen, 2013; Gamble, 2012; the most commonly acquired in women younger Mathes, 2010). than 25 years and, in some series, HSV-1 may cause lower geni- In immunocompromised individuals, treatment is more dif- tal tract infection in 13% to 40% of patients. Genital HSV-1 fcult. In the HIV-infected woman, there have been multiple is transmitted from orolabial lesions to the vulva during oral- reports of recalcitrant molluscum lesions resolving only after ini- genital contact or from genital to genital to genital contact with tiating highly active antiretroviral therapy (HAART). a partner with genital HSV-1. In primary herpes, the incubation period is between 3 and GENITAL ULCERS 7 days (average, 6 days). Although subclinical primary herpes infection is common, both local and systemic disease manifes- Herpes, (donovanosis), lymphogranuloma tations occur when the primary infection is symptomatic. Te venereum, , and syphilis may all present as ulcerations woman typically experiences paresthesia of the vulvar skin fol- in the genital area. However, their causes, disease courses, and lowed by the eruption of multiple painful vesicles, which progress treatments are diferent. Table 23.1 lists some of their major to shallow, superfcial ulcers over a large area of the vulva. Patients characteristics. Physicians must always consider the possibility experience multiple crops of ulcers for 2 to 6 weeks. Te ulcers of more than one STI concurrently infecting an individual. usually heal spontaneously without scarring (Fig. 23.7). Viral shedding may occur for 2 to 3 weeks after vulvar lesions appear Genital Herpes and, during primary infections, positive cultures for herpesvirus Genital herpes is a recurrent viral infection that is incurable may be obtained from lesions in 80% of women. Most symp- and highly contagious, with 75% of sexual partners of infected tomatic women have severe vulvar pain, tenderness, and inguinal individuals contracting the disease. It is among the most fre- adenopathy and simultaneous involvement of the vagina and cer- quently encountered STIs; a study of 5452 asymptomatic vix is common (Fig. 23.8). adults in private community-based clinics in six geographic Systemic symptoms, including general malaise and fever, regions in the United States found the seroprevalence of herpes are experienced by 70% of women during the primary infec- simplex virus type 2 (HSV-2) was 25.5%. Approximately 80% tion. Rarely, there is central nervous system (CNS) infection, of infected individuals are unaware that they are infected. Fre- with the reported mortality rate from herpes encephalitis being quently, herpes is transmitted during episodes of asymptomatic approximately 50%. Primary infections of the urethra and blad- shedding, which may occur as frequently as once in 5 days der may result in acute urinary retention, necessitating catheter- (Bernstein, 2013). It is important that the woman understand ization. Te symptoms of vulvar pain, pruritus, and discharge the natural history of disease with emphasis on the probabil- peak between days 7 and 11 of the primary infection. Te typical ity of recurrent attacks, efect of antiviral agents, and risks of woman experiences severe symptoms for approximately 14 days. neonatal infection. Although recurrent genital herpes is not Recurrent genital herpes is a local disease with less severe a debilitating physical disease, it may present a psychological symptoms. On average, a woman will have four recurrences dur- burden. Excellent online patient education and support can be ing the frst year and, in 50% of women, the frst recurrence found www.ashastd.orgGenital. Ulcers occurs within 6 months of the initial infection. Te probability

Table 23.1 Clinical Features of Genital Ulcers Type Lymphogranuloma Parameter Syphilis Herpes Chancroid Venereum Donovanosis Incubation period 2-4 wk (1-12 wk) 2-7 days 1-14 days 3 days-6 wk 1-4 wk (up to 6 mo) Primary lesion Papule Vesicle Papule or pustule Papule, pustule, or Papule vesicle Number of lesions Usually one Multiple, may coalesce Usually multiple, may Usually one Variable coalesce Diameter (mm) 5-15 1-2 2-20 2-10 Variable Edges Sharply demarcated Erythematous Undermined, ragged, Elevated, round or oval Elevated, irregular Elevated, round or oval irregular Depth Superficial or deep Superficial Excavated Superficial or deep Elevated Base Smooth, nonpurulent Serous, erythematous Purulent Variable Red and rough (beefy) Induration Firm None Sof Occasionally firm Firm Pain Unusual Common Usually very tender Variable Uncommon Lymphadenopathy Firm, nontender Firm, tender, ofen Tender, may sup- Tender, may suppurate, Pseudoadenopathy bilateral purate, usually loculated, usually bilateral unilateral unilateral

From Holmes KK, Mårdh PA, Sparling PF, et al, eds. Sexually Transmitted Diseases, 2nd ed. New York: McGraw-Hill, 1990.

Comprehensive Gynecology 7th edition, 2017 (Lobo RA, Gershenson DM, Lentz GM, Valea FA editors); chapter 23, Genital tract infections

Obstetrics & Gynecology Books Full Genital Herpes

´ recurrent viral infection that is incurable and highly contagious ´ herpes is transmitted during episodes of asymptomatic shedding ´ two distinct types of HSV: type 1 (HSV-1) and type 2 (HSV- 2). ´ HSV-1 is the most commonly acquired genital herpes in women younger than 25 years and, in some series, HSV-1 may cause lower genital tract infection in 13% to 40% of patients. ´ Genital HSV-1 is transmitted from orolabial lesions to the vulva during oral-genital contact or from genital to genital to genital contact with a partner with genital HSV-1. ´ paresthesia of the vulvar skin followed by the eruption of multiple painful vesicles, which progress to shallow,painful superficial ulcers over a large area of the vulva.

Comprehensive Gynecology 7th edition, 2017 (Lobo RA, Gershenson DM, Lentz GM, Valea FA editors); chapter 23, Genital tract infections 23 Genital Tract Infections 529

and frequency of recurrence of herpes are related to the HSV For recurrences, vulvar involvement is usually unilat- serotype. Approximately 80% of women with an initial genital eral, attacks last an average of 7 days, and viral shedding HSV-2 infection will experience a recurrence within 12 months. occurs for approximately23 Genital 5 days. Tract T Infectionse ability to culture529 her- If her primary HSV-2 infection was severe, she will have recur- pesvirus successfully from recurrent herpetic ulcers is 40%. rences approximately twice as often, with a shorter time to A common feature of recurrence is a prodromal phase of sacro- recurrenceand frequency intervals of recurrencecompared of with herpes women are related with to milder the HSV initial Forneuralgia, recurrences, vulvar vulvar burning, involvement tenderness, is usually and unilat pruritus- for a few episodesserotype. of the Approximately disease. In 80%contrast, of women if the with initial an initialpelvic genital infection eral, attackshours to last 5 an days average before of vesicle 7 days, formation. and viral shedding Extragenital sites of was HSV-1,HSV-2 infection there is will a 55% experience chance a recurrence of a recurrence within 12within months. 1 year, occurs recurrent for approximately infection 5 are days. common. Te ability T toe culture herpesvirus her- resides in a with Ifthe her average primary rateHSV-2 of recurrenceinfection was slightly severe, sheless will than have one recur episode- pesvirus latent successfully phase in from the dorsal recurrent root herpetic ganglia ulcers of S2, is S3, 40%. and S4. per yearrences (Phipps, approximately 2011; Tronstein, twice as often, 2011 with). a shorter time to A commonT featuree clinical of recurrence diagnosis is of a genitalprodromal herpes phase is ofoften sacro made- by simple recurrence intervals compared with women with milder initial neuralgia,clinical vulvar inspection. burning, tenderness,Women come and pruritusto their for physician a few when they episodes of the disease. In contrast, if the initial pelvic infection hours develop to 5 days symptoms before vesicle from formation. vulvar ulcers. Extragenital Herpetic sites ofulcers are pain- was HSV-1, there is a 55% chance of a recurrence within 1 year, recurrentful when infection touched are common. with aT cotton-tippede herpesvirus residesapplicator, in a whereas the with the average rate of recurrence slightly less than one episode latent ulcersphase inof the syphilis dorsal areroot painless. ganglia of Viral S2, S3, cultures and S4. are useful in confrm- Genital Herpes per year (Phipps, 2011; Tronstein, 2011). Tinge clinical the diagnosis of in genital primary herpes episodes is often made when by culturesimple sensitivity is clinical80%, inspection. but less Women useful come in recurrent to their physician episodes. when Most they herpesvirus cul- developtures symptoms will become from vulvar positive ulcers. within Herpetic 2 to ulcers 4 days are of pain inoculation.- Te ful whenmost touched accurate with and a cotton-tipped sensitive technique applicator, for whereas identifying the herpesvirus ulcers of syphilis are painless. Viral cultures are useful in confrm- is the polymerase chain reaction (PCR) assay. Serologic tests are ing the diagnosis in primary episodes when culture sensitivity is helpful in determining whether a woman has been infected in 80%, but less useful in recurrent episodes. Most herpesvirus cul- tures willthe becomepast with positive herpesvirus. within 2 to T 4 edays Western of inoculation. blot assay Te for antibodies ´ the ulcers usually heal spontaneously without scarring most accurateto herpes and is sensitive the most technique speci fforc identifyingmethod for herpesvirus diagnosing recurrent is the herpes,polymerase as chainwell reactionas unrecognized (PCR) assay. or Serologic subclinical tests areinfection. How- helpfulever, in determining Western blot whether tests aare woman not widelyhas been available infected andin are difcult ´ Most symptomatic women have severe vulvar pain, the pastto with perform. herpesvirus. Type-speci Te Westernfc HSV blot serologicassay for antibodies assays might be use- to herpesful inis thethe most following specifc situations:method for diagnosing(1) recurrent recurrent genital symptoms tenderness, and inguinal adenopathy and herpes,or as atypical well as unrecognizedsymptoms, withor subclinical negative infection. HSV cultures; How- (2) clinical Figure 23.7 Recurrent herpes genitalis. Superficial ulcers are ever, Westerndiagnosis blot of tests genital are not herpes widely without available laboratoryand are dif cultcon frmation; or simultaneous involvement of the vagina and cervix is noted following rupture of vesicles. (From Kaufman RH, Faro S. to perform.(3) partner Type-speci withf cgenital HSV serologicherpes. HSV assays serologic might be usetesting- should be Herpes genitalis: clinical features and treatment. Clin Obstet Gynecol. ful in consideredthe following for situations: persons (1) presenting recurrent genitalfor an symptoms STI evaluation, espe- common 1985;28:152-163.) or atypicalcially symptoms, for those withwith negative multiple HSV sex cultures; partners (2) or clinical HIV infection and Figure 23.7 Recurrent herpes genitalis. Superficial ulcers are diagnosisat increased of genital herpesrisk for without HIV laboratoryacquisition. con fScreeningrmation; or for HSV-1 or noted following rupture of vesicles. (From Kaufman RH, Faro S. (3) partnerHSV-2 with in genital the general herpes. populationHSV serologic is testingnot indicated. should be ´ Systemic symptoms, including general malaise and Herpes genitalis: clinical features and treatment. Clin Obstet Gynecol. consideredEnzyme-linked for persons presenting immunoassay for an STI (ELISA) evaluation, and espe immunoblot- tests 1985;28:152-163.) cially arefor thoseavailable with multiplefor HSV-1 sex partners and HSV-2. or HIV Rapidinfection serologic and point-of- fever at increasedcare tests risk arefor availableHIV acquisition. for HSV-2 Screening antibodies. for HSV-1 Appropriate or screen- HSV-2ing in thetests general for other population STIs isshould not indicated. be obtained, because they may Enzyme-linkedcoexist with immunoassay herpes. (ELISA) and immunoblot tests ´ symptoms of vulvar pain, pruritus, and discharge peak are availableTreatment for HSV-1 of andHSV-1 HSV-2. or HSV-2Rapid serologic may be point-of- used for three difer- care testsent are clinical available scenarios: for HSV-2 antibodies. Appropriate screen- between days 7 and 11 of the primary infection. ing tests for other STIs should be obtained, because they may coexist 1. with Primary herpes. episode Treatment 2. Recurrent of HSV-1 episode or HSV-2 may be used for three difer- ent clinical 3. Daily scenarios: suppression ´ Recurrent genital herpes is a local disease with less 1. PrimaryIn primary episode episodes, the duration and severity of symptoms are severe symptoms. On average, a woman will have 2. Recurrentlessened, episode and shedding is shortened with antiviral therapy. Anti- 3. Dailyviral suppression therapy is recommended for in all patients with primary

four recurrences during the first In primaryepisodes. episodes, the duration and severity of symptoms are lessened, andEpisodic shedding therapy is shortened for recurrenceswith antiviral cantherapy. shorten Anti- the duration viral therapyof the outbreakis recommended if started for in within all patients 24 hours with primaryof prodromal symp- episodes.toms or lesion appearance. Because of the necessity of starting Episodicantiviral therapy therapy for recurrencesimmediately can after shorten recognizing the duration symptoms, it is important that the woman with HSV be given a prescription for th of the outbreak if started within 24 hours of prodromal symp- Comprehensive Gynecology 7 edition, 2017 (Lobo RA, Gershenson DM, Lentz GM, Valea FA editors); chapter 23, Genital tract infections toms orantiviral lesion appearance.therapy to Becausehave at of home. the necessity of starting Figure 23.8 Primary herpes involving the cervix. A necrotic antiviral therapyPatient-initiated immediately therapy after recognizing has been symptoms, found toit is be superior to exophytic mass is seen on posterior lip. This was clinically thought importanttherapy that theordered woman by with a physician HSV be given because a prescription patients for initiate therapy to be invasive carcinoma. virus culture was positive. antiviralearlier therapy in tothe have course at home. of a recurrence. Te antiviral medication should be started as early as possible during the prodrome, and The lesionFigure spontaneously 23.8 Primary herpes disappeared. involving (Fromthe cervix. Kaufman A necrotic RH, Faro S. Patient-initiated therapy has been found to be superior to Herpesexophytic genitalis: mass clinical is seen featureson posterior and lip. treatment. This was clinically Clin Obstet thought Gynecol. therapyde orderedfnitely by within a physician 24 hours because of patients the appearance initiate therapy of lesions. Daily 1985;28:152-163.)to be invasive carcinoma. culture was positive. earliersuppressive in the course therapy of a recurrence. is recommended Te antiviral when medication the woman has six The lesion spontaneously disappeared. (From Kaufman RH, Faro S. should be started as early as possible during the prodrome, and Herpes genitalis: clinical features and treatment. Clin Obstet Gynecol. defnitely within 24 hours of the appearance of lesions. Daily 1985;28:152-163.) suppressive therapy is recommended when the woman has six Obstetrics & Gynecology Books Full

Obstetrics & Gynecology Books Full 23 Genital Tract Infections 529

and frequency of recurrence of herpes are related to the HSV For recurrences, vulvar involvement is usually unilat- serotype. Approximately 80% of women with an initial genital eral, attacks last an average of 7 days, and viral shedding HSV-2 infection will experience a recurrence within 12 months. occurs for approximately 5 days. Te ability to culture her- If her primary HSV-2 infection was severe, she will have recur- pesvirus successfully 23 from Genital recurrent Tract Infections herpetic ulcers529 is 40%. rences approximately twice as often, with a shorter time to A common feature of recurrence is a prodromal phase of sacro- recurrence intervals compared with women with milder initial neuralgia, vulvar burning, tenderness, and pruritus for a few episodesand frequencyof the disease. of recurrence In contrast, of herpes if the are initialrelated pelvicto the infectionHSV Forhours recurrences, to 5 days vulvar before involvement vesicle formation. is usually Extragenital unilat- sites of was HSV-1,serotype. thereApproximately is a 55% 80% chance of women of a recurrence with an initial within genital 1 year, eral, attacksrecurrent last infection an average are of common. 7 days, and T virale herpesvirus shedding resides in a with HSV-2the average infection rate will of experience recurrence a recurrence slightly less within than 12 onemonths. episode occurs latent for approximately phase in the 5dorsal days. rootTe abilityganglia to of culture S2, S3, her and- S4. per yearIf her ( Phipps,primary HSV-22011; Tronstein,infection was 2011 severe,). she will have recur- pesvirus successfullyTe clinical from diagnosis recurrent of genital herpetic herpes ulcers is isoften 40%. made by simple rences approximately twice as often, with a shorter time to A commonclinical feature inspection. of recurrence Women is a prodromal come to phasetheir ofphysician sacro- when they recurrence intervals compared with women with milder initial neuralgia,develop vulvar symptoms burning, tenderness,from vulvar and ulcers. pruritus Herpetic for a few ulcers are pain- episodes of the disease. In contrast, if the initial pelvic infection hours ful to 5when days touched before vesicle with formation. a cotton-tipped Extragenital applicator, sites of whereas the was HSV-1, there is a 55% chance of a recurrence within 1 year, recurrentulcers infection of syphilis are common. are painless. Te Viral herpesvirus cultures resides are useful in a in confrm- with the average rate of recurrence slightly less than one episode latent ingphase the in diagnosisthe dorsal rootin primary ganglia of episodes S2, S3, and when S4. culture sensitivity is Genital Herpes per year (Phipps, 2011; Tronstein, 2011). T80%,e clinical but diagnosis less useful of genital in recurrent herpes is often episodes. made byMost simple herpesvirus cul- clinicaltures inspection. will become Women positive come to within their physician 2 to 4 days when of they inoculation. Te developmost symptoms accurate from and vulvar sensitive ulcers. technique Herpetic ulcers for identifying are pain- herpesvirus ful whenis the touched polymerase with a cotton-tippedchain reaction applicator, (PCR) whereasassay. Serologic the tests are ´ the clinical diagnosis of genital herpes is often ulcers helpfulof syphilis in are determining painless. Viral whether cultures are a usefulwoman in conhasf rmbeen- infected in ing thethe diagnosis past with in primary herpesvirus. episodes T whene Western culture sensitivityblot assay is for antibodies 80%, but less useful in recurrent episodes. Most herpesvirus cul- to herpes is the most specifc method for diagnosing recurrent made by simple clinical inspection. tures will become positive within 2 to 4 days of inoculation. Te most accurateherpes, andas wellsensitive as techniqueunrecognized for identifying or subclinical herpesvirus infection. How- is the ever,polymerase Western chain blot reaction tests (PCR)are not assay. widely Serologic available tests areand are difcult ´ Herpetic ulcers are painful when touched with a helpfulto in perform. determining Type-speci whether fa cwoman HSV has serologic been infected assays in might be use- the pastful with in theherpesvirus. following T esituations: Western blot (1) assay recurrent for antibodies genital symptoms cotton-tipped applicator, whereas the ulcers of to herpesor atypical is the most symptoms, specifc method with negativefor diagnosing HSV recurrent cultures; (2) clinical Figure 23.7 Recurrent herpes genitalis. Superficial ulcers are herpes,diagnosis as well as of unrecognized genital herpes or subclinical without infection.laboratory How con- frmation; or noted following rupture of vesicles. (From Kaufman RH, Faro S. ever, Western(3) partner blot testswith are genital not widely herpes. available HSV and serologic are dif culttesting should be syphilis are painless. Herpes genitalis: clinical features and treatment. Clin Obstet Gynecol. to perform.considered Type-speci for fpersonsc HSV serologicpresenting assays for might an STI be useevaluation,- espe- 1985;28:152-163.) ful in ciallythe following for those situations: with multiple (1) recurrent sex partners genital symptoms or HIV infection and ´ the most accurate and sensitive technique for or atypicalat increased symptoms, risk with for negative HIV acquisition.HSV cultures; Screening (2) clinical for HSV-1 or Figure 23.7 Recurrent herpes genitalis. Superficial ulcers are diagnosisHSV-2 of genital in the herpes general without population laboratory is connotf indicated.rmation; or identifying herpes virus is the polymerase chain noted following rupture of vesicles. (From Kaufman RH, Faro S. (3) partnerEnzyme-linked with genital herpes. immunoassay HSV serologic (ELISA) testing shouldand immunoblot be tests Herpes genitalis: clinical features and treatment. Clin Obstet Gynecol. consideredare available for persons for presenting HSV-1 andfor an HSV-2. STI evaluation, Rapid serologicespe- point-of- reaction (PCR) assay. 1985;28:152-163.) cially carefor those tests with are multipleavailable sex for partners HSV-2 or antibodies. HIV infection Appropriate and screen- at increaseding tests risk forfor otherHIV acquisition. STIs should Screening be obtained, for HSV-1 because or they may HSV-2coexist in the generalwith herpes. population is not indicated. ´ the Western blot assay for antibodies to herpes Enzyme-linkedTreatment immunoassay of HSV-1 (ELISA) or HSV-2 and immunoblotmay be used tests for three difer- are availableent clinical for HSV-1 scenarios: and HSV-2. Rapid serologic point-of- care tests are available for HSV-2 antibodies. Appropriate screen- is the most specific method for diagnosing ing tests 1. for Primary other STIsepisode should be obtained, because they may coexist 2. with Recurrent herpes. episode recurrent herpes, as well as unrecognized or 3. Daily suppression Treatment of HSV-1 or HSV-2 may be used for three difer- ent clinical scenarios: subclinical infection. In primary episodes, the duration and severity of symptoms are 1. Primarylessened, episode and shedding is shortened with antiviral therapy. Anti- 2. Recurrentviral therapy episode is recommended for in all patients with primary 3. Dailyepisodes. suppression Episodic therapy for recurrences can shorten the duration In primary episodes, the duration and severity of symptoms are of the outbreak if started within 24 hours of prodromal symp- lessened, and shedding is shortened with antiviral therapy. Anti- viral therapytoms or is lesionrecommended appearance. for in allBecause patients of with the primarynecessity of starting episodes.antiviral therapy immediately after recognizing symptoms, it is Episodicimportant therapy that for the recurrences woman with can shorten HSV be the given duration a prescription for antiviral therapy to have at home. th of the outbreak if started within 24 hours of prodromal symp- Comprehensive Gynecology 7 edition, 2017 (Lobo RA, Gershenson DM, Lentz GM, Valea FAFigure editors); 23.8 chapterPrimary herpes 23, involving Genital the cervix.tract A infectionsnecrotic toms or lesionPatient-initiated appearance. Because therapy of hasthe necessity been found of starting to be superior to exophytic mass is seen on posterior lip. This was clinically thought antiviraltherapy therapy ordered immediately by a afterphysician recognizing because symptoms, patients it initiateis therapy to be invasive carcinoma. Herpes simplex virus culture was positive. importantearlier that in the the woman course with of HSV a recurrence. be given a prescription Te antiviral for medication The lesion spontaneously disappeared. (From Kaufman RH, Faro S. antiviralshould therapy be to started have at ashome. early as possible during the prodrome, and Herpes genitalis: clinical features and treatment. Clin Obstet Gynecol. defnitely within 24 hours of the appearance of lesions. Daily Figure 23.8 Primary herpes involving the cervix. A necrotic Patient-initiated therapy has been found to be superior to 1985;28:152-163.) exophytic mass is seen on posterior lip. This was clinically thought therapysuppressive ordered by atherapy physician is becauserecommended patients initiate when therapy the woman has six to be invasive carcinoma. Herpes simplex virus culture was positive. earlier in the course of a recurrence. Te antiviral medication The lesion spontaneously disappeared. (From Kaufman RH, Faro S. should be started as early as possible during the prodrome, and Herpes genitalis: clinical features and treatment. Clin Obstet Gynecol. defnitely within 24 hours of the appearance of lesions. Daily 1985;28:152-163.) suppressive therapy is recommended when the woman has six Obstetrics & Gynecology Books Full

Obstetrics & Gynecology Books Full Genital Herpes

´ Treatment of HSV-1 or HSV-2 may be used for three different clinical scenarios: ´ 1. Primary episode ´ 2. Recurrent episode ´ 3. Daily suppression ´ Antiviral therapy is recommended for in all patients with primary episodes. ´ Episodic therapy for recurrences can shorten the duration of the outbreak if started within 24 hours of prodromal symptoms or lesion appearance. ´ antiviral medication should be started as early as possible during the prodrome, and definitely within 24 hours of the appearance of lesions.

Comprehensive Gynecology 7th edition, 2017 (Lobo RA, Gershenson DM, Lentz GM, Valea FA editors); chapter 23, Genital tract infections Genital Herpes

´ CDC recommends that acyclovir or other suppressive drugs be discontinued after 12 months of suppressive therapy to determine 530 Part III theGENERAL subsequent GYNECOLOGY rate of recurrence for each individual woman

Table 23.2 Antiviral Treatment for Herpes Simplex Virus in the Nonpregnant Patient Antiviral Agent Indication Valacyclovir Acyclovir Famciclovir First clinical episode 1000 mg bid, 7-10 days 200 mg five times/day; or 400 mg tid, 250 mg tid, 7-10 days 7-10 days Recurrent episodes 1000 mg daily, 5 days; or 500 mg bid, 400 mg tid, 5 days; 800 mg bid, 5 days; 125 mg bid, 5 days 3 days or 800 mg tid, 2 days 500 mg once then 250 mg bid, 2 days; 1000 mg bid, 1 day Daily suppressive 1000 mg daily (≥10 recurrences/year) or 400 mg bid 250 mg bid 500 mg daily (≤9 recurrences/year)

Data from Workowski KA, Bolan GA, Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep. 2015; 64(RR-03):1-137. bid, Twice per day; tid, three times per day.

Comprehensive Gynecology 7th edition, 2017 (Lobo RA, Gershenson DM, Lentz GM, Valea FA editors); chapter 23, Genital tract infections

or more episodes annually or for psychological distress. It is important for patients to be aware that asymptomatic viral shed- ding can occur even when on daily suppressive therapy (Bavaro, 2008; Gupta, 2004). In serodiscordant couples a prospective placebo-controlled randomized trial has demonstrated that daily use of valacyclovir for suppression in the seropositive partner results in signifcantly fewer cases of HSV acquisition in the seronegative partner. Regu- lar use of condoms in serodiscordant couples also decreases trans- mission but is not 100% protective. HSV-seronegative women are three times as likely to acquire HSV infection from seroposi- tive male partners compared with seronegative males acquiring HSV from infected female partners. A summary of CDC-recom- mended treatment regimens is presented in Table 23.2. Acyclovir is a drug with relatively minimal toxicity and reports have documented its safety in patients receiving daily Figure 23.9 Donovanosis. Biopsy specimen shows intracytoplasmic therapy with acyclovir for as long as 6 years and with valacyclo- Donovan bodies (H&E stain). (From Hart G. Donovanosis. In: Holmes vir or famciclovir for 1 year. However, the CDC recommends KK, Mårdh PA, Sparling PF, et al, eds. Sexually Transmitted Diseases. that acyclovir or other suppressive drugs be discontinued after New York: McGraw-Hill; 1984.) 12 months of suppressive therapy to determine the subsequent rate of recurrence for each individual woman (Workowski, 2015). Even if herpes is not treated over time, clinical recur- ulcer a beefy red appearance, and it bleeds easily when touched. rences tend to dramatically decrease in number. Unless secondarily infected, the ulcers are painless and without A vaccine would be the logical approach for optimum pre- regional adenopathy. Typically, multiple nodules are present, vention of herpes. Research is ongoing. resulting in ulcers that grow and coalesce and, if untreated, will eventually destroy the normal vulvar architecture. If untreated, Granuloma Inguinale (Donovanosis) the chronic form of the disease is characterized by scarring and Granuloma inguinale, also known as donovanosis, is a chronic, lymphatic obstruction, which produces marked enlargement of ulcerative, bacterial infection of the skin and subcutaneous tis- the vulva. In endemic areas, the disease is usually diagnosed by sue of the vulva. Rarely, the vagina and cervix are involved in its clinical manifestations. Te diagnosis may also be established advanced untreated cases. Granuloma inguinale is common in by identifying Donovan bodies in smears and specimens taken tropical climates such as New Guinea and the Caribbean Islands, from the ulcers (Fig. 23.9). Donovan bodies appear as clusters but fewer than 20 cases are reported each year in the United of dark-staining bacteria with a bipolar (safety pin) appearance States. Tis disease can be spread sexually and through close found in the cytoplasm of large mononuclear cells. Te diferen- nonsexual contact. However, it is not highly contagious, and tial diagnosis includes , vulvar car- chronic exposure is usually necessary to contract the disease. Te cinoma, syphilis, chancroid, genital herpes, amebiasis, and other incubation period is extremely variable, from 1 to 12 weeks. It granulomatous diseases. is caused by an intracellular, gram-negative, nonmotile, encap- A wide range of oral broad-spectrum antibiotics may be sulated rod, , which is difcult to culture used to manage granuloma inguinale. Te CDC recommends on standard media. Tere are no U.S. Food and Drug Admin- azithromycin 1 g orally once a week or 500 mg daily for 3 istration (FDA)–approved molecular tests for the detection of weeks and until all lesions have healed. Alternative antibiotic K. granulomatis DNA. Serologic tests are nonspecifc. regimens include the following: doxycycline, 100 mg orally, Te initial growth of granuloma inguinale is a nodule that twice daily for a minimum of 3 weeks; ciprofoxacin, 750 mg gradually progresses into a painless, slowly progressing ulcer orally twice daily; erythromycin base, 500 mg orally four times surrounded by highly vascular granulation tissue. Tis gives the daily; or trimethoprim-sulfamethoxazole (TMP-SMZ), one

Obstetrics & Gynecology Books Full Granuloma Inguinale (Donovanosis) ´ also known as donovanosis, is a chronic, ulcerative, bacterial infection of the skin and subcutaneous tissue of the vulva. ´ can be spread sexually and through close nonsexual contact. However, it is not highly contagious, and chronic exposure is usually necessary to contract the disease. ´ caused by an intracellular, gram-negative, nonmotile, encapsulated rod, Klebsiella granulomatis. ´ initial growth is a nodule that gradually progresses into a painless, slowly progressing ulcer surrounded by highly vascular granulation tissue à The ulcer has a beefy red appearance, and it bleeds easily when touched. ´

Comprehensive Gynecology 7th edition, 2017 (Lobo RA, Gershenson DM, Lentz GM, Valea FA editors); chapter 23, Genital tract infections Granuloma Inguinale (Donovanosis)

´ the ulcers are painless and without regional adenopathy. Typically, multiple nodules are present, resulting in ulcers that grow and coalesce and, if untreated, will eventually destroy the normal vulvar architecture. ´ diagnosis may also be established by identifying Donovan bodies in smears and specimens taken from the ulcers ´ Donovan bodies appear as clusters of dark-staining bacteria with a bipolar (safety pin) appearance found in the cytoplasm of large mononuclear cells.

Comprehensive Gynecology 7th edition, 2017 (Lobo RA, Gershenson DM, Lentz GM, Valea FA editors); chapter 23, Genital tract infections Granuloma Inguinale (Donovanosis)

´ CDC recommends azithromycin 1 g orally once a week or 500 mg daily for 3 weeks and until all lesions have healed. ´ Alternative antibiotic regimens include the following: 1. doxycycline, 100 mg orally, twice daily for a minimum of 3 weeks; 2. ciprofloxacin, 750 mg orally twice daily; 3. erythromycin base, 500 mg orally four times daily; 4. trimethoprim-sulfamethoxazole (TMP- SMZ), one double-strength tablet orally twice daily.

Comprehensive Gynecology 7th edition, 2017 (Lobo RA, Gershenson DM, Lentz GM, Valea FA editors); chapter 23, Genital tract infections Lymphogranuloma Venereum 23 Genital Tract Infections 531

double-strength tablet orally twice daily. Terapy should be continued until the lesions have healed completely. Alternative antibiotic therapy such as an aminoglycoside has been used in ´ This sexually transmittedrefractory cases. infection Rarely, medical therapy is fails and surgical exci- sion is required. Co-infection with another sexually transmitted caused by serotypespathogen L1, is a L2,distinct possibility.and Sex L3 partners of women who have granuloma inguinale should be examined if they have had sexual contact during the 60 days preceding the onset of symp- of C. trachomatis. toms (Workowski, 2015).

Lymphogranuloma Venereum ´ In women, the vulvaLymphogranuloma is the most venereum (LGV) is a chronic infection of lymphatic tissue produced by . It is found most commonly in the tropics. Cases occur infrequently in the frequent site of infection,United States, with but fewer than the 150 new cases being reported each year, most of which occur in men. In women, the vulva is the urethra, rectum, andmost cervix frequent site of infection, may but the urethra, rectum, and cervix may also be involved. Tis sexually transmitted infection is caused by serotypes L1, L2, and L3 of C. trachomatis. Serologic studies also be involved. in high-risk populations have found that subclinical infection is common. Te incubation period is between 3 and 30 days. Tere are three distinct phases of vulvar and perirectal LGV. Te primary infection is a shallow, painless ulcer that heals rap- idly without therapy. It is typically located on the vestibule or labia but occasionally in the periurethral or perirectal region. Figure 23.10 Lymphogranuloma venereum bubo with groove One to 4 weeks after the primary infection, a secondary phase sign. (From Friedrich EG. Vulvar Disease. 2nd ed. Philadelphia: WB marked by painful adenopathy develops in the inguinal and Saunders; 1983.) perirectal areas. Two thirds of women have unilateral adenop- athy and 50% have systemic symptoms, including general Fluoroquinolone-based treatments may also be efective, but malaise and fever. When the disease is untreated, the infected extended treatment intervals are likely required (Workowski, nodes become increasingly tender, enlarged, matted together, 2015). and adherent to overlying skin, forming a bubo (tender lymph Antibiotic therapy cures the bacterial infection and prevents nodes). A classic clinical sign of LGV is the double genitocrural further tissue destruction. However, fuctuant nodes should be fold, or groove sign (Fig. 23.10), a depression between groups aspirated to prevent sinus formation. Rarely, incision and drain- of infamed nodes. Within 7 to 15 days, the bubo will rupture age of infected nodes are necessary to alleviate inguinal pain. spontaneously and form multiple draining sinuses and fstulas. Te late sequelae of the destructive tertiary phase of LGV often th Comprehensive Gynecology 7 edition, 2017 (LoboTese RA, are Gershensonclassic signs of the DM,tertiary Lentz phase ofGM, the infection. Valea FArequire editors); extensive chapter surgical reconstruction. 23, Genital It is tract important infections to Extensive tissue destruction of the external genitalia and ano- administer antibiotics during the perioperative period. rectal region may occur during the tertiary phase. Tis tissue destruction and secondary extensive scarring and fbrosis may Chancroid result in elephantiasis, multiple fstulas, and stricture forma- Chancroid is a sexually transmitted, acute, ulcerative disease of the tion of the anal canal and rectum. vulva caused by , a highly contagious, small, Diagnosis is established by detecting C. trachomatis by culture, nonmotile, gram-negative rod. Chancroid is a common disease in direct immunofuorescence, or nucleic acid detection from the developing countries but infrequent in the United States. Epide- pus or aspirate from a tender lymph node. Chlamydia serology miologic studies have suggested that chancroid tends to occur in (complement fxation titers >1:64) can support the diagnosis in clusters and may account for a substantial portion of genital ulcer the appropriate clinical context. However, the diagnostic useful- cases when present. However, difculty in making the diagnosis ness of serologic methods other than complement fxation and may cause underreporting. Te clinical importance of chancroid some microimmunofuorescence procedures remains unclear. In has been enhanced by reports that the genital ulcers of chancroid the absence of specifc LGV diagnostic testing, patients should facilitate the transmission of HIV infection. be treated based on the clinical presentation, including procto- Te soft chancre of chancroid is always painful and tender. In colitis or genital ulcer disease with lymphadenopathy. Te difer- comparison, the hard chancre of syphilis is usually asymptom- ential diagnosis of LGV includes syphilis, chancroid, granuloma atic. On Gram stain, this facultative anaerobic bacterium exhib- inguinale, bacterial lymphadenitis, vulvar carcinoma, genital its a classic appearance of streptobacillary chains, or what has herpes, and Hodgkin disease. been described as an extracellular school of fsh. Te incubation Te CDC recommends doxycycline, 100 mg twice daily period is short, usually 3 to 6 days. Tissue trauma and excoria- for at least 21 days, as the preferred treatment. An alterna- tion of the skin must precede initial infection because H. ducreyi tive therapy choice is erythromycin base, 500 mg four times is unable to penetrate and invade normal skin. daily orally for 21 days. Azithromycin, 1 g orally once weekly Te initial lesion is a small papule. Within 48 to 72 hours, for 3 weeks, is probably efective, but clinical data are lacking. the papule evolves into a pustule and subsequently ulcerates.

Obstetrics & Gynecology Books Full 23 Genital Tract Infections 531

double-strength tablet orally twice daily. Terapy should be continued until the lesions have healed completely. Alternative antibiotic therapy such as an aminoglycoside has been used in refractory cases. Rarely, medical therapy fails and surgical exci- sion is required. Co-infection with another sexually transmitted pathogen is a distinct possibility. Sex partners of women who have granuloma inguinale should be examined if they have had sexual contact during the 60 days preceding the onset of symp- toms (Workowski, 2015).

Lymphogranuloma Venereum Lymphogranuloma venereum (LGV) is a chronic infection of Lymphogranuloma lymphaticVenereum tissue produced by Chlamydia trachomatis. It is found most commonly in the tropics. Cases occur infrequently in the United States, with fewer than 150 new cases being reported each year, most of which occur in men. In women, the vulva is the most frequent site of infection, but the urethra, rectum, and cervix may also be involved. Tis sexually transmitted infection is caused by serotypes L1, L2, and L3 of C. trachomatis. Serologic studies in high-risk populations have found that subclinical infection is common. Te incubation period is between 3 and 30 days. ´ There are 3 distinct phases of vulvar andT perirectalere are three distinct phases LGV: of vulvar and perirectal LGV. Te primary infection is a shallow, painless ulcer that heals rap- idly without therapy. It is typically located on the vestibule or labia but occasionally in the periurethral or perirectal region. Figure 23.10 Lymphogranuloma venereum bubo with groove One to 4 weeks after the primary infection, a secondary phase sign. (From Friedrich EG. Vulvar Disease. 2nd ed. Philadelphia: WB ´ the primary infection: shallow, painlessmarked byulcer painful adenopathy that develops heals in the inguinal rapidly and Saunders; without 1983.) perirectal areas. Two thirds of women have unilateral adenop- athy and 50% have systemic symptoms, including general Fluoroquinolone-based treatments may also be efective, but therapy; typically located on the vestibulemalaise and fever. Whenor thelabia disease is untreated, the infected extended treatment intervals are likely required (Workowski, nodes become increasingly tender, enlarged, matted together, 2015). and adherent to overlying skin, forming a bubo (tender lymph Antibiotic therapy cures the bacterial infection and prevents nodes). A classic clinical sign of LGV is the double genitocrural further tissue destruction. However, fuctuant nodes should be fold, or groove sign (Fig. 23.10), a depression between groups aspirated to prevent sinus formation. Rarely, incision and drain- ´ a secondary phase: painful adenopathyof infamed nodes. that Within 7develops to 15 days, the bubo will rupturein the age ofinguinal infected nodes are necessaryand to alleviate inguinal pain. spontaneously and form multiple draining sinuses and fstulas. Te late sequelae of the destructive tertiary phase of LGV often Tese are classic signs of the tertiary phase of the infection. require extensive surgical reconstruction. It is important to perirectal areas Extensive tissue destruction of the external genitalia and ano- administer antibiotics during the perioperative period. rectal region may occur during the tertiary phase. Tis tissue destruction and secondary extensive scarring and fbrosis may Chancroid result in elephantiasis, multiple fstulas, and stricture forma- Chancroid is a sexually transmitted, acute, ulcerative disease of the tion of the anal canal and rectum. vulva caused by Haemophilus ducreyi, a highly contagious, small, ´the infected nodes become tender,Diagnosis enlarged, is established by detecting C. matted trachomatis by culture, together,nonmotile, gram-negative and rod. Chancroid is a common disease in direct immunofuorescence, or nucleic acid detection from the developing countries but infrequent in the United States. Epide- pus or aspirate from a tender lymph node. Chlamydia serology miologic studies have suggested that chancroid tends to occur in (complement fxation titers >1:64) can support the diagnosis in clusters and may account for a substantial portion of genital ulcer adherent to overlying skin, formingthe appropriate a bubo clinical context.(tender However, the diagnostic lymph useful- cases nodes). when present. However, difculty in making the diagnosis ness of serologic methods other than complement fxation and may cause underreporting. Te clinical importance of chancroid some microimmunofuorescence procedures remains unclear. In has been enhanced by reports that the genital ulcers of chancroid the absence of specifc LGV diagnostic testing, patients should facilitate the transmission of HIV infection. be treated based on the clinical presentation, including procto- Te soft chancre of chancroid is always painful and tender. In ´groove sign: double genitocruralcolitis fold or genital à ulcer diseasea depression with lymphadenopathy. Te di fbetweener- comparison, the hardgroups chancre of syphilis is usually asymptom- ential diagnosis of LGV includes syphilis, chancroid, granuloma atic. On Gram stain, this facultative anaerobic bacterium exhib- inguinale, bacterial lymphadenitis, vulvar carcinoma, genital its a classic appearance of streptobacillary chains, or what has of inflamed nodes. à classic signherpes, of and LGV Hodgkin disease. been described as an extracellular school of fsh. Te incubation Te CDC recommends doxycycline, 100 mg twice daily period is short, usually 3 to 6 days. Tissue trauma and excoria- for at least 21 days, as the preferred treatment. An alterna- tion of the skin must precede initial infection because H. ducreyi tive therapy choice is erythromycin base, 500 mg four times is unable to penetrate and invade normal skin. daily orally for 21 days. Azithromycin, 1 g orally once weekly Te initial lesion is a small papule. Within 48 to 72 hours, ´ tertiary phase : bubo ruptures spontaneouslyfor 3 weeks, is probably ef ective,and but clinical form data are multiplelacking. the papule draining evolves into a pustule and subsequently ulcerates. sinuses and fistulas à classic signs of extensive tissue destruction of the Obstetrics & Gynecology Books Full external genitalia and anorectal region may occur during the tertiary phase.

Comprehensive Gynecology 7th edition, 2017 (Lobo RA, Gershenson DM, Lentz GM, Valea FA editors); chapter 23, Genital tract infections Lymphogranuloma Venereum 23 Genital Tract Infections 531

´ Diagnosis is established bydouble-strength detecting tablet orally C. twice daily. Terapy should be continued until the lesions have healed completely. Alternative trachomatis by culture, directantibiotic therapy such as an aminoglycoside has been used in refractory cases. Rarely, medical therapy fails and surgical exci- immunofluorescence, or sionnucleic is required. Co-infection acid withdetection another sexually transmitted pathogen is a distinct possibility. Sex partners of women who from the pus or aspirate fromhave granuloma a tender inguinale should lymph be examined ifnode. they have had sexual contact during the 60 days preceding the onset of symp- ´ In the absence of specifictoms LGV (Workowski, diagnostic 2015). testing, Lymphogranuloma Venereum patients should be treatedLymphogranuloma based venereum on the (LGV) clinical is a chronic infection of lymphatic tissue produced by Chlamydia trachomatis. It is found presentation most commonly in the tropics. Cases occur infrequently in the United States, with fewer than 150 new cases being reported each year, most of which occur in men. In women, the vulva is the ´ Treatment: most frequent site of infection, but the urethra, rectum, and cervix may also be involved. Tis sexually transmitted infection is caused by serotypes L1, L2, and L3 of C. trachomatis. Serologic studies ´ CDC recommends doxycycline,in high-risk populations have 100 found mg that subclinical twice infection is common. Te incubation period is between 3 and 30 days. daily for at least 21 days,Tere as are three the distinct preferred phases of vulvar and perirectal LGV. Te primary infection is a shallow, painless ulcer that heals rap- treatment. idly without therapy. It is typically located on the vestibule or labia but occasionally in the periurethral or perirectal region. Figure 23.10 Lymphogranuloma venereum bubo with groove ´ An alternative therapyOne choice to 4 weeks after isthe erythromycinprimary infection, a secondary phase sign. (From Friedrich EG. Vulvar Disease. 2nd ed. Philadelphia: WB marked by painful adenopathy develops in the inguinal and Saunders; 1983.) base, 500 mg four timesperirectal daily areas. Two orally thirds of women for have21 unilateral days. adenop - athy and 50% have systemic symptoms, including general Fluoroquinolone-based treatments may also be efective, but malaise and fever. When the disease is untreated, the infected extended treatment intervals are likely required (Workowski, nodes become increasingly tender, enlarged, matted together, 2015). and adherent to overlying skin, forming a bubo (tender lymph Antibiotic therapy cures the bacterial infection and prevents Comprehensive Gynecology 7th edition, 2017 (Lobonodes). RA, AGershenson classic clinical signDM, of LGV Lentz is the GM, double Valea genitocruralFA editors);further tissue chapter destruction. 23, However,Genital fuctuant tract nodesinfections should be fold, or groove sign (Fig. 23.10), a depression between groups aspirated to prevent sinus formation. Rarely, incision and drain- of infamed nodes. Within 7 to 15 days, the bubo will rupture age of infected nodes are necessary to alleviate inguinal pain. spontaneously and form multiple draining sinuses and fstulas. Te late sequelae of the destructive tertiary phase of LGV often Tese are classic signs of the tertiary phase of the infection. require extensive surgical reconstruction. It is important to Extensive tissue destruction of the external genitalia and ano- administer antibiotics during the perioperative period. rectal region may occur during the tertiary phase. Tis tissue destruction and secondary extensive scarring and fbrosis may Chancroid result in elephantiasis, multiple fstulas, and stricture forma- Chancroid is a sexually transmitted, acute, ulcerative disease of the tion of the anal canal and rectum. vulva caused by Haemophilus ducreyi, a highly contagious, small, Diagnosis is established by detecting C. trachomatis by culture, nonmotile, gram-negative rod. Chancroid is a common disease in direct immunofuorescence, or nucleic acid detection from the developing countries but infrequent in the United States. Epide- pus or aspirate from a tender lymph node. Chlamydia serology miologic studies have suggested that chancroid tends to occur in (complement fxation titers >1:64) can support the diagnosis in clusters and may account for a substantial portion of genital ulcer the appropriate clinical context. However, the diagnostic useful- cases when present. However, difculty in making the diagnosis ness of serologic methods other than complement fxation and may cause underreporting. Te clinical importance of chancroid some microimmunofuorescence procedures remains unclear. In has been enhanced by reports that the genital ulcers of chancroid the absence of specifc LGV diagnostic testing, patients should facilitate the transmission of HIV infection. be treated based on the clinical presentation, including procto- Te soft chancre of chancroid is always painful and tender. In colitis or genital ulcer disease with lymphadenopathy. Te difer- comparison, the hard chancre of syphilis is usually asymptom- ential diagnosis of LGV includes syphilis, chancroid, granuloma atic. On Gram stain, this facultative anaerobic bacterium exhib- inguinale, bacterial lymphadenitis, vulvar carcinoma, genital its a classic appearance of streptobacillary chains, or what has herpes, and Hodgkin disease. been described as an extracellular school of fsh. Te incubation Te CDC recommends doxycycline, 100 mg twice daily period is short, usually 3 to 6 days. Tissue trauma and excoria- for at least 21 days, as the preferred treatment. An alterna- tion of the skin must precede initial infection because H. ducreyi tive therapy choice is erythromycin base, 500 mg four times is unable to penetrate and invade normal skin. daily orally for 21 days. Azithromycin, 1 g orally once weekly Te initial lesion is a small papule. Within 48 to 72 hours, for 3 weeks, is probably efective, but clinical data are lacking. the papule evolves into a pustule and subsequently ulcerates.

Obstetrics & Gynecology Books Full Chancroid

´ Chancroid is a sexually transmitted, acute, ulcerative disease of the vulva caused by Haemophilus ducreyi, a highly contagious, small, nonmotile, gram-negative rod. ´ the soft chancre of chancroid is always painful and tender. ´ the hard chancre of syphilis is usually asymptomatic. ´ Gram stain: facultative anaerobic bacterium with a classic appearance of streptobacillary chains (extracellular school of fish). ´ Tissue trauma and excoriation of the skin must preceed initial infection because H. ducreyi is unable to penetrate and invade normal skin.

Comprehensive Gynecology 7th edition, 2017 Chancroid

´ the initial lesion is a small papule. Within 48 to 72 hours, the papule evolves into a pustule and subsequently ulcerates. ´ the extremely painful ulcers are shallow, with a characteristic ragged edge, and usually occur in the vulvar vestibule and rarely in the vagina or cervix. ´ ulcers have a dirty, gray, necrotic, foul-smelling exudate and lack induration at the base (the soft chancre). ´ approximately 50% of women develop acutely tender inguinal adenopathy (a bubo) which is typically unilateral. ´ Fluctuant nodes should be treated by needle aspiration to prevent rupture or by incision and drainage if larger than 5 cm.

Comprehensive Gynecology 7th edition, 2017 (Lobo RA, Gershenson DM, Lentz GM, Valea FA editors); chapter 23, Genital tract infections Chancroid

´ A definitive diagnosis of chancroid requires the identification of H. ducreyi on special culture media that are not widely available from commercial sources; ´ the clinical diagnosis is made in a woman with painful vulvar ulcers after excluding other common STIs that produce vulvar ulcers, including genital herpes, syphilis, LGV, and donovanosis. ´ Treatment: CDC recommends the following: ´ azithromycin, 1 g orally in a single dose; or ´ ceftriaxone, 250 mg intramuscular (IM) in a single dose; or ´ ciprofloxacin, 500 mg orally twice daily for 3 days; or ´ erythromycin base, 500 mg orally three times daily for 7 days.

Comprehensive Gynecology 7th edition, 2017 (Lobo RA, Gershenson DM, Lentz GM, Valea FA editors); chapter 23, Genital tract infections 532 Part III GENERAL GYNECOLOGY

Te extremely painful ulcers are shallow, with a characteristic Syphilis ragged edge, and usually occur in the vulvar vestibule and rarely in the vagina or cervix. Te ulcers have a dirty, gray, necrotic, foul- smelling exudate and lack induration at the base (the soft chancre). Multiple papules and ulcers may be in diferent phases of maturation secondary to autoinoculation. Within 2 weeks of an untreated infection, approximately 50% of women develop acutely tender inguinal adenopathy, a bubo, which is typically ´ chronic, complex systemicunilateral. disease Fluctuant nodes producedshould be treated by needle by aspiration to prevent rupture or by incision and drainage if larger than 5 cm. the spirochete TreponemaA depallidum.fnitive diagnosis of chancroid requires the identifcation of H. ducreyi on special culture media that are not widely avail- able from commercial sources; even when these media are used, ´ T. pallidum is an anaerobic,sensitivity elongated, is less than 80%. No FDA-approved tightly PCR test for H. ducreyi is available in the United States, but this testing can wound spirochete. be performed by clinical laboratories that have developed their own PCR test and conducted a Clinical Laboratory Improve- Figure 23.11 Dark-field microscopic appearance of Treponema ´ Because of its extreme thinness,ment Amendments T (CLIA)pallidum verifcation study. is Sometimes, the pallidum. (From Larsen SA, McGrew BE, Hunter EF, et al. Syphilis clinical diagnosis is made in a woman with painful vulvar ulcers serology and dark field microscopy. In: Holmes KK, Mårdh PA, difficult to detect by lightafter microscopy excluding other common STIs à that produce vulvar ulcers, Sparling PF, et al, eds. Sexually Transmitted Diseases. New York: including genital herpes, syphilis, LGV, and donovanosis. McGraw-Hill; 1984.) therefore the presence of Duespirochetes to antibiotic resistance to tetracyclinesis and sulfonamides, the CDC recommends the following: azithromycin, 1 g orally in membranes. Te incubation period is from 10 to 90 days, with diagnosed by use of speciallya single dose adapted or ceftriaxone, 250 mg intramuscular (IM) in a an average of 3 weeks. Tey replicate every 30 to 36 hours, which single dose or ciprofoxacin, 500 mg orally twice daily for 3 days; accounts for the comparatively long incubation period. techniques, dark-field microscopy,or erythromycin base, 500 or mg orally direct three times daily for 7 days. Syphilis is a moderately contagious disease. Approximately Sexual partners should be treated in a similar fashion. Successful 3% to 10% of patients contract the disease from a single sex- fluorescent antibody testsantibiotic therapy results in symptomatic and objective improve- ual encounter with an infected partner. Similar studies have ment within 5 to 7 days of initiating therapy. Large ulcers may documented that 30% of individuals become infected during a require 2 to 3 weeks to heal, with clinical resolution of lymph- 1-month exposure to a sexual partner with primary or secondary ´ Patients are contagious duringadenopathy slower primary, than that of ulcers. Buboes respond at a syphilis. Patients are contagious during primary, secondary, and slower rate than skin ulcers (Workowski, 2015). Approximately probably the frst year of latent syphilis. Syphilis can be spread secondary, and probably10% the of women first whose year ulcers initially of heal latent have a recurrence at by kissing or touching a person who has an active lesion on the the same site. Women with HIV infection have an increased rate lips, oral cavity, breast, or genitals. Case transmission can occur syphilis. of failure to the standard treatments for chancroid and there- with oral-genital contact. fore often require more prolonged therapy. Co-infection with Te diagnosis of syphilis is complicated by the fact that the another ulcer causing an STI should be considered, especially in organism cannot be cultivated in vitro. Defnitive diagnosis is ´ Syphilis can be spread bywomen kissing lacking an appropriateor touching response to treatment. a via darkfeld microscopy to detect T. palladium in lesion exu- date or tissue. T. palladium detection kits are not commercially person who has an activeSyphilis lesion on the lips, oral available, but some labs provide locally developed PCR tests. cavity, breast, or genitals.Syphilis is a chronic, complex systemic disease produced by the Terefore presumptive diagnosis and screening rely on sero- spirochete . Te infection initially involves logic tests. Tere are two types of serologic tests, the nonspecifc mucous membranes. Syphilis remains one of the important STIs nontreponemal and the specifc antitreponemal antibody tests. in the United States, and epidemiologists speculate that only Te nontreponemal tests, such as the Venereal Disease Research th Comprehensive Gynecology 7 edition, 2017 (Lobo RA,one Gershensonof four new cases ofDM, syphilis Lentz is reported. GM, Early Valea syphilis FAis a editors);Laboratory chapter (VDRL) slide 23, test andGenital the rapid tractplasma reagininfections (RPR) cofactor in the transmission and acquisition of HIV and, cur- card test are inexpensive and easy to perform. Tey are used as rently, 25% of new syphilis cases occur in persons co-infected screening tests for the disease, typically become positive 4 to with HIV. Even with mandatory screening, congenital syphilis 6 weeks after exposure, and also are a useful index of treatment continues to be a public health problem. Mothers who experi- response. Tese tests evaluate the woman’s serum for the pres- ence stillbirth or neonatal death from syphilis usually have not ence of reagin IgG and IgM antibodies as they react with an received prenatal care. Syphilis should be included in the dif- antigen from beef heart. Quantitative nontreponemal antibody ferential diagnosis of all genital ulcers and cutaneous rashes of titers usually correlate with the activity of the disease. Serologic unknown origin, and all women diagnosed with syphilis should testing is an indirect method of diagnosis because it relies on a be screened for HIV. humoral immune response to infection. As such, it has some T. pallidum is an anaerobic, elongated, tightly wound spiro- inherent limitations. Approximately 1% of patients have techni- chete. Because of its extreme thinness, it is difcult to detect cal or biologic false-positive results with the nonspecifc tests. by light microscopy. Terefore the presence of spirochetes is Many conditions produce biologic false-positive results, includ- diagnosed by use of specially adapted techniques, dark-feld ing a recent febrile illness, pregnancy, immunization, chronic microscopy, or direct fuorescent antibody tests (Fig. 23.11). active hepatitis, malaria, sarcoidosis, intravenous (IV) drug Tese organisms have the ability to penetrate skin or mucous use, HIV infection, advancing age, acute herpes simplex, and

Obstetrics & Gynecology Books Full 532 Part III GENERAL GYNECOLOGY

Te extremely painful ulcers are shallow, with a characteristic ragged edge, and usually occur in the vulvar vestibule and rarely in the vagina or cervix. Te ulcers have a dirty, gray, necrotic, foul- smelling exudate and lack induration at the base (the soft chancre). Multiple papules and ulcers may be in diferent phases of maturation secondary to autoinoculation. Within 2 weeks of Syphilis an untreated infection, approximately 50% of women develop acutely tender inguinal adenopathy, a bubo, which is typically unilateral. Fluctuant nodes should be treated by needle aspiration to prevent rupture or by incision and drainage if larger than 5 cm. A defnitive diagnosis of chancroid requires the identifcation of H. ducreyi on special culture media that are not widely avail- ´ Definitive diagnosisable isfrom via commercial darkfield sources; even whenmicroscopy these media are used, to sensitivity is less than 80%. No FDA-approved PCR test for detect T. palladiumH. ducreyi in lesion is available inexudate the United States, orbut thistissue. testing can be performed by clinical laboratories that have developed their own PCR test and conducted a Clinical Laboratory Improve- Figure 23.11 Dark-field microscopic appearance of Treponema ´ Presumptive diagnosisment Amendments and (CLIA)screening verifcation study. rely Sometimes, on the pallidum. (From Larsen SA, McGrew BE, Hunter EF, et al. Syphilis clinical diagnosis is made in a woman with painful vulvar ulcers serology and dark field microscopy. In: Holmes KK, Mårdh PA, serologic tests: after excluding other common STIs that produce vulvar ulcers, Sparling PF, et al, eds. Sexually Transmitted Diseases. New York: including genital herpes, syphilis, LGV, and donovanosis. McGraw-Hill; 1984.) Due to antibiotic resistance to tetracyclines and sulfonamides, the CDC recommends the following: azithromycin, 1 g orally in membranes. Te incubation period is from 10 to 90 days, with nonspecific nontreponemala single tests dose or: ceftriaxone,VDRL 250and mg intramuscularRPR (used (IM) in as a screeningan average of 3 weeks. tests Tey replicate and every index 30 to 36 hours, of which single dose or ciprofoxacin, 500 mg orally twice daily for 3 days; accounts for the comparatively long incubation period. treatment response) or erythromycin base, 500 mg orally three times daily for 7 days. Syphilis is a moderately contagious disease. Approximately Sexual partners should be treated in a similar fashion. Successful 3% to 10% of patients contract the disease from a single sex- • false-positive results: recentantibiotic therapy febrile results inillness, symptomatic pregnancy, and objective improve- immunization,ual encounter with an infected chronic partner. Similar active studies have ment within 5 to 7 days of initiating therapy. Large ulcers may documented that 30% of individuals become infected during a hepatitis, malaria, sarcoidosis,require 2 to 3 weeks intravenous to heal, with clinical resolution(IV) drug of lymph use,- 1-month HIV exposure infection, to a sexual partner advancing with primary or secondary adenopathy slower than that of ulcers. Buboes respond at a syphilis. Patients are contagious during primary, secondary, and age, acute herpes simplex,slower rate thanand skin ulcersautoimmune (Workowski, 2015). Approximately diseases probablysuch the as frst lupusyear of latent erythematosus syphilis. Syphilis can be spread or 10% of women whose ulcers initially heal have a recurrence at by kissing or touching a person who has an active lesion on the rheumatoid arthritis. the same site. Women with HIV infection have an increased rate lips, oral cavity, breast, or genitals. Case transmission can occur of failure to the standard treatments for chancroid and there- with oral-genital contact. fore often require more prolonged therapy. Co-infection with Te diagnosis of syphilis is complicated by the fact that the another ulcer causing an STI should be considered, especially in organism cannot be cultivated in vitro. Defnitive diagnosis is • false-negative result: occurswomen lacking in an women appropriate response in towhom treatment. there isvia an dark fexcesseld microscopy of to detectanticardiolipin T. palladium in lesion exu - date or tissue. T. palladium detection kits are not commercially antibody in the serum,Syphilis termed the prozone phenomenonavailable,. but some labs provide locally developed PCR tests. Syphilis is a chronic, complex systemic disease produced by the Terefore presumptive diagnosis and screening rely on sero- spirochete Treponema pallidum. Te infection initially involves logic tests. Tere are two types of serologic tests, the nonspecifc mucous membranes. Syphilis remains one of the important STIs nontreponemal and the specifc antitreponemal antibody tests. • Women with immunocompromisein the United States, and also epidemiologists may speculate have that false only -Tnegativee nontreponemal tests,tests such asbecause the Venereal Disease of Research their one of four new cases of syphilis is reported. Early syphilis is a Laboratory (VDRL) slide test and the rapid plasma reagin (RPR) inability to produce thecofactor antibodies in the transmission detected and acquisition of HIVby and,these cur- screeningcard test are inexpensive tests. and easy to perform. Tey are used as rently, 25% of new syphilis cases occur in persons co-infected screening tests for the disease, typically become positive 4 to with HIV. Even with mandatory screening, congenital syphilis 6 weeks after exposure, and also are a useful index of treatment continues to be a public health problem. Mothers who experi- response. Tese tests evaluate the woman’s serum for the pres- ence stillbirth or neonatal death from syphilis usually have not ence of reagin IgG and IgM antibodies as they react with an received prenatal care. Syphilis should be included in the dif- antigen from beef heart. Quantitative nontreponemal antibody ferential diagnosis of all genital ulcers and cutaneous rashes of titers usually correlate with the activity of the disease. Serologic unknown origin, and all women diagnosed with syphilis should testing is an indirect method of diagnosis because it relies on a be screened for HIV. humoral immune response to infection. As such, it has some T. pallidum is an anaerobic, elongated, tightly wound spiro- inherent limitations. Approximately 1% of patients have techni- chete. Because of its extreme thinness, it is difcult to detect cal or biologic false-positive results with the nonspecifc tests. by light microscopy. Terefore the presence of spirochetes is Many conditions produce biologic false-positive results, includ- diagnosed by use of specially adapted techniques, dark-feld ing a recent febrile illness, pregnancy, immunization, chronic microscopy, or direct fuorescent antibody tests (Fig. 23.11). active hepatitis, malaria, sarcoidosis, intravenous (IV) drug Tese organisms have the ability to penetrate skin or mucous use, HIV infection, advancing age, acute herpes simplex, and

Obstetrics & Gynecology Books Full Syphilis

532 Part III GENERAL GYNECOLOGY

´ If a nonspecific test resultTe extremely is painfulpositive, ulcers are shallow, the with a characteristic ragged edge, and usually occur in the vulvar vestibule and rarely significance of this resultin the vagina must or cervix. be Te ulcers have a dirty, gray, necrotic, foul- smelling exudate and lack induration at the base (the soft confirmed by a specific chancre). antitreponemalMultiple papules and ulcers may be in diferent phases of maturation secondary to autoinoculation. Within 2 weeks of tests: fluorescent-labeledan untreated Treponema infection, approximately 50% of women develop acutely tender inguinal adenopathy, a bubo, which is typically antibody absorption unilateral.(FTA Fluctuant-ABS) nodes testshould be andtreated by needle aspiration to prevent rupture or by incision and drainage if larger than 5 cm. the micro- hemagglutinationA defnitive diagnosis assay of chancroid for requires the identifcation of H. ducreyi on special culture media that are not widely avail- able from commercial sources; even when these media are used, antibodies to T. pallidumsensitivity is(MHA less than 80%.- TP) No FDA-approved PCR test for H. ducreyi is available in the United States, but this testing can be performed by clinical laboratories that have developed their ´ false-positive results: lupusown PCR test and conducted a Clinical Laboratory Improve- Figure 23.11 Dark-field microscopic appearance of Treponema ment Amendments (CLIA) verifcation study. Sometimes, the pallidum. (From Larsen SA, McGrew BE, Hunter EF, et al. Syphilis erythematosus clinical diagnosis is made in a woman with painful vulvar ulcers serology and dark field microscopy. In: Holmes KK, Mårdh PA, after excluding other common STIs that produce vulvar ulcers, Sparling PF, et al, eds. Sexually Transmitted Diseases. New York: including genital herpes, syphilis, LGV, and donovanosis. McGraw-Hill; 1984.) ´ A woman with a positiveDue to antibioticreactive resistance to tetracyclines and sulfonamides, the CDC recommends the following: azithromycin, 1 g orally in membranes. Te incubation period is from 10 to 90 days, with treponemal test usuallya single will dose or have ceftriaxone, 250this mg intramuscular (IM) in a an average of 3 weeks. Tey replicate every 30 to 36 hours, which single dose or ciprofoxacin, 500 mg orally twice daily for 3 days; accounts for the comparatively long incubation period. positive reaction for heror erythromycin lifetime, base, 500 mg orally three times daily for 7 days. Syphilis is a moderately contagious disease. Approximately Sexual partners should be treated in a similar fashion. Successful 3% to 10% of patients contract the disease from a single sex- regardless of treatmentantibiotic or therapy activity results in symptomatic of theand objective improve- ual encounter with an infected partner. Similar studies have ment within 5 to 7 days of initiating therapy. Large ulcers may documented that 30% of individuals become infected during a disease require 2 to 3 weeks to heal, with clinical resolution of lymph- 1-month exposure to a sexual partner with primary or secondary adenopathy slower than that of ulcers. Buboes respond at a syphilis. Patients are contagious during primary, secondary, and slower rate than skin ulcers (Workowski, 2015). Approximately probably the frst year of latent syphilis. Syphilis can be spread 10% of women whose ulcers initially heal have a recurrence at by kissing or touching a person who has an active lesion on the Comprehensive Gynecology 7th edition, 2017 (Lobothe RA, same Gershenson site. Women with HIVDM, infection Lentz have GM, an increased Valea rateFA editors);lips, oral cavity, chapter breast, or genitals. 23, Genital Case transmission tract caninfections occur of failure to the standard treatments for chancroid and there- with oral-genital contact. fore often require more prolonged therapy. Co-infection with Te diagnosis of syphilis is complicated by the fact that the another ulcer causing an STI should be considered, especially in organism cannot be cultivated in vitro. Defnitive diagnosis is women lacking an appropriate response to treatment. via darkfeld microscopy to detect T. palladium in lesion exu- date or tissue. T. palladium detection kits are not commercially Syphilis available, but some labs provide locally developed PCR tests. Syphilis is a chronic, complex systemic disease produced by the Terefore presumptive diagnosis and screening rely on sero- spirochete Treponema pallidum. Te infection initially involves logic tests. Tere are two types of serologic tests, the nonspecifc mucous membranes. Syphilis remains one of the important STIs nontreponemal and the specifc antitreponemal antibody tests. in the United States, and epidemiologists speculate that only Te nontreponemal tests, such as the Venereal Disease Research one of four new cases of syphilis is reported. Early syphilis is a Laboratory (VDRL) slide test and the rapid plasma reagin (RPR) cofactor in the transmission and acquisition of HIV and, cur- card test are inexpensive and easy to perform. Tey are used as rently, 25% of new syphilis cases occur in persons co-infected screening tests for the disease, typically become positive 4 to with HIV. Even with mandatory screening, congenital syphilis 6 weeks after exposure, and also are a useful index of treatment continues to be a public health problem. Mothers who experi- response. Tese tests evaluate the woman’s serum for the pres- ence stillbirth or neonatal death from syphilis usually have not ence of reagin IgG and IgM antibodies as they react with an received prenatal care. Syphilis should be included in the dif- antigen from beef heart. Quantitative nontreponemal antibody ferential diagnosis of all genital ulcers and cutaneous rashes of titers usually correlate with the activity of the disease. Serologic unknown origin, and all women diagnosed with syphilis should testing is an indirect method of diagnosis because it relies on a be screened for HIV. humoral immune response to infection. As such, it has some T. pallidum is an anaerobic, elongated, tightly wound spiro- inherent limitations. Approximately 1% of patients have techni- chete. Because of its extreme thinness, it is difcult to detect cal or biologic false-positive results with the nonspecifc tests. by light microscopy. Terefore the presence of spirochetes is Many conditions produce biologic false-positive results, includ- diagnosed by use of specially adapted techniques, dark-feld ing a recent febrile illness, pregnancy, immunization, chronic microscopy, or direct fuorescent antibody tests (Fig. 23.11). active hepatitis, malaria, sarcoidosis, intravenous (IV) drug Tese organisms have the ability to penetrate skin or mucous use, HIV infection, advancing age, acute herpes simplex, and

Obstetrics & Gynecology Books Full 23 Genital Tract Infections 533

Table 23.3 Potential Causes of Biologic False-Positive Results in Syphilis Serology Biologic False-Positive Reaction Cause Acute Chronic Physiologic Pregnancy Advanced age, multiple transfusions Infectious Varicella, vaccinia, measles, mumps, infectious mononucleosis, HIV, tropical spastic paraparesis, leprosy,* tuberculosis, herpes simplex, viral hepatitis, HIV seroconversion illness, malaria,* lymphogranuloma venereum, trypanosomiasis,* cytomegalovirus, pneumococcal pneumonia, Mycoplasma kala-azar* pneumoniae, chancroid, lymphogranuloma venereum, psittacosis, bacterial endocarditis, scarlet fever, rickettsial infections, toxoplasmosis, Lyme disease, leptospirosis, relapsing fever, rat bite fever Vaccinations Smallpox, typhoid, yellow fever Autoimmune Systemic lupus erythematosus, discoid lupus, drug-induced disease lupus, autoimmune hemolytic anemia, polyarteritis nodosa, rheumatoid arthritis, Sjögren syndrome, Hashimoto thyroiditis, mixed connective tissue disease, primary biliary cirrhosis, chronic liver disease, idiopathic thrombocytopenic purpura Other IV drug use, advanced malignancy hypergammaglobu- linemia, lymphoproliferative disease

Data from Nandwani R, Evans DTP. Are you sure it’s syphilis? A review of false-positive serology. Int J STD AIDS. 1995;6:241; Hook EW III, Marra CM. Acquired syphilis in adults. N Engl J Med. 1992;326:1062. *Biologic false-positive reaction resolves with resolution of infection. HIV, Human immunodeficiency virus.

th Comprehensiveautoimmune Gynecology diseases 7 suchedition, as lupus 2017 erythematosus (Lobo RA, Gershenson or rheuma- DM,ulcer Lentz is primaryGM, Valea or secondaryFA editors); syphilis chapter depends 23, on Genital the identi tractfca -infections toid arthritis. Biologic false-positive serum tests usually are asso- tion of T. pallidum by dark-feld microscopy from wet smears ciated with extremely low titers (<1:8). A false-negative result of the ulcer. Special preparations must be made to obtain suit- is a possibility, occurring in approximately 1% to 2% of tests. able smears. It is important to clean and abrade the ulcer with Tis negative reaction occurs in women in whom there is an gauze before obtaining the serum for the slides. At the time of excess of anticardiolipin antibody in the serum, termed the pro- dark-feld identifcation of T. pallidum from a primary chancre, zone phenomenon. Women with immunocompromise also may approximately 70% of women will have a positive serologic test. have false-negative tests because of their inability to produce the If the serologic test result remains negative for 3 months, it is antibodies detected by these screening tests. unlikely that the ulcer was syphilis. Syphilis is not frequently If a nonspecifc test result is positive, the signifcance of this diagnosed in the primary stage in women. result must be confrmed by a specifc antitreponemal test. Anti- If primary syphilis is untreated, approximately 25% of indi- treponemal tests are more sensitive; however, occasionally, they viduals develop secondary syphilis, which is the result of hema- may produce false-positive results. Most false-positive results togenous dissemination of the spirochetes. Secondary syphilis is occur in women with lupus erythematosus (Table 23.3). Te a systemic disease that develops between 6 weeks and 6 months standard for antitreponemal tests are the fuorescent-labeled (average, 9 weeks) after the primary chancre. Te stages are not Treponema antibody absorption (FTA-ABS) test and the micro- exclusive. Approximately 25% of women still have a primary hemagglutination assay for antibodies to T. pallidum (MHA- chancre when the secondary lesions appear. An untreated attack TP). Te MHA-TP does not have as high a rate of false-positive of secondary syphilis will last 2 to 6 weeks, and a multitude of results as the FTA-ABS. A woman with a positive reactive trepo- systemic symptoms may occur, depending on the major organs nemal test usually will have this positive reaction for her lifetime, involved, such as rash, fever, headache, malaise, lymphadenopa- regardless of treatment or activity of the disease. thy, and anorexia. Te classic rash of secondary syphilis is red Clinically, syphilis is divided into primary, secondary, and macules and papules over the palms of the hands and the soles tertiary stages. In primary syphilis, a papule, which is usually of the feet (Fig. 23.13). Vulvar lesions of condyloma latum are painless, appears at the site of inoculation 2 to 3 weeks after large, raised, fattened, grayish white areas (Fig. 23.14). On wet exposure. Tis soon ulcerates to produce the classic fnding of surfaces of the vulva, soft papules often coalesce to form ulcers. primary syphilis, a chancre that is a painless ulcer, 1 to 2 cm, with Tese ulcers are larger than herpetic ulcers and are not tender a raised indurated margin and a nonexudative base (Fig. 23.12). unless secondarily infected. A woman with syphilis is most Usually, the chancre is solitary, painless, and found on the vulva, infectious during the frst 1 to 2 years of disease, with decreasing vagina, or cervix, although extragenital primary lesions, includ- infectivity thereafter. ing lesions of the mouth, anal canal, and breast nipple, have been Te latent stage of syphilis follows the secondary stage and reported in approximately 5% of patients. Nontender and frm varies in duration from 2 to 20 years; it is characterized as posi- regional adenopathy is present during the frst week of clinical tive serology without symptoms or signs of disease. Women with disease. Within 2 to 6 weeks, the painless ulcer heals spontane- syphilis in the primary or secondary stages and during the frst ously. Hence, many women do not seek treatment, a feature that year of latent syphilis are believed to be infectious. Most women enhances the likelihood of transmission. Confrmation that the diagnosed with syphilis are detected via positive blood tests during

Obstetrics & Gynecology Books Full Syphilis

´ Clinically, syphilis is divided into primary, secondary, and tertiary stages: ´ Primary syphilis: ´ a papule, which is usually painless, appears at the site of inoculation 2 to 3 weeks after exposure. à soon ulcerates to produce the classic chancre that is a painless ulcer, with a raised indurated margin and a nonexudative base ´ the chancre is solitary, painless, and found on the vulva, vagina, or cervix ´ Nontender and firm regional adenopathy is present during the first week of clinical disease. ´ Within 2 to 6 weeks, the painless ulcer heals spontaneouslyà Hence, many women do not seek treatment

Comprehensive Gynecology 7th edition, 2017 (Lobo RA, Gershenson DM, Lentz GM, Valea FA editors); chapter 23, Genital tract infections Syphilis ´ Secondary syphilis: ´ If primary syphilis is untreated, approximately 25% of individuals develop secondary syphilis ´ result from hematogenous dissemination of the spirochetes. ´ systemic symptoms may occur such as rash, fever, headache, malaise, lymphadenopathy, and anorexia. ´ the classic rash of secondary syphilis is red macules and papules over the palms of the hands and the soles of the feet ´ Vulvar lesions of condyloma latum are large, raised, flattened, grayish white areas ´ On wet surfaces of the vulva, soft papules often coalesce to form ulcers à larger than herpetic ulcers and are not tender unless secondarily infected. Syphilis ´ Latent syphilis: ´ Follows after secondary syphilis, and varies in duration from 2 to 20 years ´ characterized as positive serology without symptoms or signs of disease. ´ Women with syphilis in the primary or secondary stages and during the first year of latent syphilis are believed to be infectious. ´ Most women diagnosed with syphilis are detected via positive blood tests during the latent stage of the disease. ´ Early latent syphilis is an infection of 1 year or less. ´ All other cases are referred to as late latent or latent syphilis of unknown duration.

Comprehensive Gynecology 7th edition, 2017 (Lobo RA, Gershenson DM, Lentz GM, Valea FA editors); chapter 23, Genital tract infections Syphilis

´ Tertiary phase ´ devastating in its potentially destructive effects on the central nervous, cardiovascular, and musculoskeletal systems. ´ manifestations of late syphilis include optic atrophy, tabes dorsalis, generalized paresis, aortic aneurysm, and gummas of the skin and bones. ´ A gumma is similar to a cold abscess, with a necrotic center and the obliteration of small vessels by endarteritis.

Comprehensive Gynecology 7th edition, 2017 (Lobo RA, Gershenson DM, Lentz GM, Valea FA editors); chapter 23, Genital tract infections Syphilis

´ Treatment: ´ Parenteral penicillin G is the drug of choice for syphilis.

´ CDC recommends 2.4 million units of benzathine penicillin G IM in one dose for early syphilis (primary and early latent secondary syphilis). ´ Patients who are allergic to penicillin should receive oral tetracycline, 500 mg every 6 hours for 14 days, or ´ doxycycline, 100 mg orally twice a day for 2 weeks.

´ Approximately 60% of women develop an acute febrile reaction associated with flulike symptoms such as headache and myalgia within the first 24 hours after parenteral penicillin therapy for early syphilis (Jarisch-Herxheimer reaction)

Comprehensive Gynecology 7th edition, 2017 (Lobo RA, Gershenson DM, Lentz GM, Valea FA editors); chapter 23, Genital tract infections 536 Part III GENERAL GYNECOLOGY

Box 23.2 Centers for Disease Control and Prevention experience relapses of secondary syphilis. Women who have a Recommended Treatment of Syphilis (2014) sustained fourfold increase in nontreponemal test titers have failed treatment or become reinfected. Tey should be retreated Early Syphilis (primary, secondary, and early latent syphilis and evaluated for concurrent HIV infection. When women are of less than 1 year in duration) Recommended regimen: Benzathine penicillin G, 2.4 million U IM, retreated, the recommendation is three weekly injections of ben- one dose zathine penicillin G, 2.4 million units IM. For long-term follow- Alternative regimen (penicillin-allergic nonpregnant patients): up, the same serologic tests should be ordered. Optimally, the Doxycycline, 100 mg orally bid for 2 wk or tetracycline, 500 mg test should be obtained from the same laboratory. Te VDRL orally qid for 2 wk and RPR tests are equally valid, but RPR titers tend to be slightly Late Latent Syphilis (>1 year in duration, gummas, and higher than VDRL titers. With successful treatment, the VDRL cardiovascular syphilis) titer will become nonreactive or, at most, be reactive, with a Recommended regimen: Benzathine penicillin G, 7.2 million U lower titer within 1 year. Tere is a 1% to 2% chance that the total, administered as three doses of 2.4 million U IM at 1-wk woman will not exhibit a fourfold titer decline, and these cases intervals are considered therapeutic failures. Tey should be retreated. Alternative regimen (penicillin-allergic nonpregnant patients): Patients with syphilis lasting longer than 1 year should have Doxycycline 100 mg orally 2 times a day for 2 wk if <1 year, quantitative VDRL titers for 2 years following therapy because otherwise, for 4 wk; or tetracycline, 500 mg orally qid for 2 wk their titers will decline more slowly. A specifc test for syphilis, if <1 year; otherwise, for 4 wk such as the FTA-ABS, remains reactive indefnitely. In summary, Neurosyphilis all women with a frst attack of primary syphilis should have a Recommended regimen: Aqueous crystalline penicillin G, 18-24 negative nonspecifc serology within 1 year, and women treated million U daily, administered as 3-4 million U IV every 4 hr, for for secondary syphilis should have a negative serology within 10-14 days 2 years. If they are not, treatment failure, reinfection, and con- Alternative regimen: Procaine penicillin, 2.4 million U IM daily, for current HIV infection should be investigated. 10-14 days plus probenecid, 500 mg PO qid for 10-14 days Syphilis often involves the CNS. Tere is no established diag- Syphilis in Pregnancy nostic test that is a gold standard for neurosyphilis. Te diagnosis Recommended regimen: Penicillin regimen appropriate for stage of neurosyphilis is based on a combination of clinical fndings, of syphilis. Some experts recommend additional therapy (e.g., reactive serologic tests, and abnormalities of cerebrospinal fuid, second dose of benzathine penicillin, 2.4 million U IM) 1 wk serology, cell count, or protein. Infection of the CNS by spiro- afer the initial dose for those who have primary, secondary, or chetes may occur during any stage of syphilis. Women should early latent syphilis Alternative regimen (penicillin allergy): Pregnant women with undergo a cerebrospinal fuid examination if they develop neu- a history of penicillin allergy should be skin-tested and rologic or ophthalmologic signs or symptoms, evidence of active desensitized tertiary syphilis, treatment failures, and HIV infection with late latent syphilis or syphilis of an unknown duration. To treat neuro- Syphilis in HIV-Infected Patients syphilis, the CDC recommends aqueous crystalline penicillin G, Primary and secondary syphilis: Benzathine penicillin G, 2.4 million U IM. Some experts recommend additional treat- 18 to 24 million units daily, administered as 3 to 4 million units ments, such as three weekly doses of benzathine penicillin G. IV every 4 hours for 10 to 14 days. An alternative regimen is pro- Penicillin-allergic patients should be desensitized and treated caine penicillin, 2.4 million units IM daily, plus probenecid, 500 with penicillin mg orally four times daily for 10 to 14 days. Te duration of both Latent syphilis (normal CSF examination): Benzathine penicillin G, these regimens for neurosyphilis is shorter than that of the regimen 7.2 million U as three weekly doses of 2.4 million U each used for late syphilis in the absence of neurosyphilis. Terefore some experts administer benzathine penicillin, 2.4 million units thData from Workowski KA, Bolan GA, Centers for Disease Control and Prevention. Comprehensive Gynecology 7 Sexuallyedition, transmitted 2017 (Lobo diseases RA, treatment Gershenson guidelines, DM,2015. LentzMMWR GM,Recomm Valea Rep. FA editors);IM, after chaptercompletion 23, of Genital either regimentract infections to provide a comparable 2015;64(RR-03):1-137. total duration of therapy (Workowski, 2015). bid, Twice per day; CSF, cerebrospinal fluid; qid, four times per day. It is important for all women with syphilis to be tested for HIV infection. Simultaneous syphilis and HIV infections alter the natural history of syphilis, with earlier involvement of the 500 mg every 6 hours for 14 days, or doxycycline, 100 mg orally CNS. Women with HIV infection may have a slightly increased twice a day for 2 weeks. Standard treatment protocols for syphilis rate of treatment failure with currently recommended regimens. are detailed in Box 23.2. Approximately 60% of women develop Similarly, they may exhibit unusual serologic responses. Usually, an acute febrile reaction associated with fulike symptoms such serologic titers are higher than expected. However, false-negative as headache and myalgia within the frst 24 hours after paren- serologic tests or delayed appearance of seroreactivity has been teral penicillin therapy for early syphilis. Tis response is known reported. Nevertheless, the CDC’s recommendation for treating as the Jarisch-Herxheimer reaction (Workowski, 2015). early syphilis in women is the same whether or not they are con- All women with early syphilis should be reexamined clini- currently infected with HIV. Following penicillin treatment for cally and serologically at 6 and 12 months following therapy. syphilis, women with HIV should be followed with quantitative With successful therapy in early syphilis, the titer should decline titers at more frequent intervals—for example, at 3, 6, 9, 12, and fourfold in 6 months and become negative within 12 months. 24 months following therapy. Women with latent syphilis should have quantitative nontrepo- Sexual partners of women with syphilis in any stage should nemal serologic tests 6, 12, and 24 months following therapy. be evaluated clinically and serologically. Te time intervals used During the frst 3 to 4 years of the latent phase, a woman may to identify an at-risk sex partner are 3 months plus duration of

Obstetrics & Gynecology Books Full Syphilis

´ Treatment: ´ Women who have a sustained fourfold increase in nontreponemal test titers have failed treatment or become reinfected à should be retreated and evaluated for concurrent HIV infection. ´ When women are retreated, the recommendation is three weekly injections of benzathine penicillin G, 2.4 million units IM. ´ With successful treatment, the VDRL titer will become nonreactive or, at most, be reactive, with a lower titer within 1 year. ´ all women with a first attack of primary syphilis should have a negative nonspecific serology within 1 year, and women treated for secondary syphilis should have a negative serology within 2 years à if they are not, treatment failure, reinfection, and concurrent HIV infection should be investigated.

Comprehensive Gynecology 7th edition, 2017 (Lobo RA, Gershenson DM, Lentz GM, Valea FA editors); chapter 23, Genital tract infections Neurosyphilis

´ Syphilis often involves the CNS.

´ the diagnosis of neurosyphilis is based on a combination of clinical findings, reactive serologic tests, and abnormalities of cerebrospinal fluid, serology, cell count, or protein. ´ CDC recommends aqueous crystalline penicillin G, 18 to 24 million units daily, administered as 3 to 4 million units IV every 4 hours for 10 to 14 days.

´ An alternative regimen is procaine penicillin, 2.4 million units IM daily, plus probenecid, 500 mg orally four times daily for 10 to 14 days. ´ It is important for all women with syphilis to be tested for HIV infection. Simultaneous syphilis and HIV infections alter the natural history of syphilis, with earlier involvement of the CNS.

Comprehensive Gynecology 7th edition, 2017 (Lobo RA, Gershenson DM, Lentz GM, Valea FA editors); chapter 23, Genital tract infections Infections of the vagina VAGINITIS

´ Vaginal discharge is the most common symptom in gynecology.

´ Other symptoms associated with vaginal infection include superficial dyspareunia, dysuria, odor, and vulvar burning and pruritus. ´ the three common causes of vaginitis are (1) a fungus (candidiasis), (2) a protozoon 538 (Trichomonas),Part III GENERAL and GYNECOLOGY (3) a disruption of the vaginal bacterial ecosystem leading to bacterial vaginosis.

Table 23.5 Typical Features of Vaginitis Condition Symptoms and Signs* Findings on Examination* pH Wet Mount Comment Bacterial Increased discharge Thin, whitish gray, homoge- >4.5 Clue cells (>20%) shif in flora Greatly decreased vaginosis† (white, thin), neous discharge, cocci, Amine odor afer adding lactobacilli Increased odor sometimes frothy potassium hydroxide to Greatly increased cocci wet mount Small curved rods Candidiasis Increased discharge Thick, curdy discharge <4.5 Hyphae or spores Can be mixed infection (white, thick)‡ Vaginal erythema with bacterial vaginosis, Dysuria T. vaginalis, or both, and Pruritus have higher pH Burning Trichomoniasis§ Increased discharge Yellow, frothy discharge, >4.5 Motile trichomonads More symptoms at higher (yellow, frothy) with or without vaginal or Increased white cells vaginal pH Increased odor cervical erythema Dysuria Pruritus

From Eckert LO. Clinical practice: acute vulvovaginitis. N Engl J Med. 2006;355(12):1244-1252. *Although these features are typical, their sensitivity and specificity are generally inadequate for diagnosis. †For a diagnosis of bacterial vaginosis, a report of increased discharge has a sensitivity of 50% and a specificity of 49%; odor, a sensitivity of 49% and a specificity of 20%; and pH >4.7, a sensitivity of 97%, and a specificity of 65%, compared with the use of a Gram stain. ‡Of patients presenting with symptoms of vaginitis, 40% report increased (white) discharge, but this discharge is not related to Candida albicans in many studies. §A report of a yellow discharge has a sensitivity of 42% and a specificity of 80%; a frothy discharge on examination has a sensitivity of 8% and a specificity of 99%.

BACTERIAL VAGINOSIS infections, including endometritis, pelvic infammatory disease, Bacterial vaginosis is the most prevalent cause of symptom- postoperative vaginal cuf cellulitis, and multiple complications atic vaginitis, with a prevalence of approximately 15% to 50% of infection during pregnancy, such as preterm rupture of the ( Allsworth, 2007). Bacterial vaginosis refects a shift in vagi- membranes, endomyometritis, decreased success with in vitro nal fora from lactobacilli-dominant to mixed fora, including fertilization, and increased pregnancy loss of less than 20 weeks’ genital mycoplasmas, G. vaginalis, and anaerobes, such as pep- gestation. tostreptococci, and Prevotella and Mobiluncus spp. Although In women with bacterial vaginosis, the most frequent symp- Gardnerella and anaerobic organisms can be found in women tom is an unpleasant vaginal odor, which patients describe as with normal vaginal fora, their concentration increases several- musty or fshy (Table 23.6). Te odor is often stronger follow- fold in women with bacterial vaginosis concurrent with a marked ing intercourse, when the alkaline semen results in a release of decrease in lactobacilli. aromatic amines. Te origin of bacterial vaginosis remains elusive. No caus- Te vaginal discharge associated with bacterial vaginosis is thin ative agent has been identifed. Because of the inability to fnd and gray-white. Speculum examination reveals that the discharge a transmissible agent, bacterial vaginosis has not been classifed is mildly adherent to the vaginal walls, in contrast to a physiologic as an STI. Currently, bacterial vaginosis is described as a “sexu- discharge, which is in the most dependent areas of the vagina. ally associated” infection rather than a true sexually transmitted Te vaginal discharge is frothy in approximately 10% of women, infection. Risk factors for bacterial vaginosis include new or mul- and it is rare to have associated pruritus or vulvar irritation. tiple sexual partners. It also is prevalent in women who have sex Bacterial vaginosis is clinically diagnosed. Te classic fndings with women; genotyping has revealed identical bacterial strains on wet smear are clumps of bacteria and clue cells, which are between monogamous lesbian partners. Also, bacterial vagino- vaginal epithelial cells with clusters of bacteria adherent to their sis is more common in lesbian couples who share sex toys with external surfaces (Fig. 23.16). Leukocytes are not nearly as fre- each other without cleaning the toys between use (Bailey, 2004; quent as epithelial cells underneath the microscope. Marrazzo, 2010a, 2010b). Molecular techniques have identi- Te four criteria for the diagnosis of bacterial vaginosis are fed a cluster of noncultivable bacteria related to Clostridium in (1) a homogeneous vaginal discharge is present; (2) the vaginal women with bacterial vaginosis (Fredricks, 2005; Hillier, 2005). discharge has a pH of 4.5 or higher; (3) the vaginal discharge has As newer techniques analyzing vaginal fora evolve, it may be an amine-like odor when mixed with potassium hydroxide, the possible to determine a causal agent. whif test; and (4) a wet smear of the vaginal discharge demon- Other risk factors include douching as least monthly or strates clue cells more than 20% of the number of the vaginal within the prior 7 days, and social stressors (e.g., homelessness, epithelial cells. For the clinician, three of these four criteria are threats to personal safety, insufcient fnancial resources). A lack sufcient for a presumptive diagnosis. Fifty percent of women of hydrogen peroxide–producing lactobacilli is also a recognized who have three of the four clinical criteria for bacterial vaginosis risk factor for bacterial vaginosis and may explain, in part, the are asymptomatic. If available, Gram staining of vaginal secre- higher prevalence of bacterial vaginosis in black women inde- tion is an excellent diagnostic method. A colorimetric test that pendent of other risk factors. detects proline iminopeptidase has been developed for ofce use. Histologically, there is an absence of infammation in biop- Enzyme levels in vaginal fuid are elevated in women with bacte- sies of the vagina—thus the term vaginosis rather than vagini- rial vaginosis. Vaginal bacterial culture has no role in the evalua- tis. Bacterial vaginosis has been associated with upper tract tion of bacterial vaginosis.

Obstetrics & Gynecology Books Full BACTERIAL VAGINOSIS

´ Bacterial vaginosis is the most prevalent cause of symptomatic vaginitis ´ Bacterial vaginosis reflects a shift in vaginal flora from lactobacilli- dominant to mixed flora, including genital mycoplasmas, G. vaginalis, and anaerobes, such as peptostreptococci, and Prevotella and Mobiluncus spp. ´ Currently, bacterial vaginosis is described as a “sexually associated” infection rather than a true sexually transmitted infection. ´ Histologically, there is an absence of inflammation in biopsies of the vagina—thus the term vaginosis rather than vaginitis. ´ Bacterial vaginosis has been associated with upper tract infections, including endometritis, pelvic inflammatory disease, postoperative vaginal cuff cellulitis, and multiple complications of infection during pregnancy, such as preterm rupture of the membranes, endomyometritis, decreased success with in vitro fertilization, and increased pregnancy loss of less than 20 weeks’ gestation. BACTERIAL VAGINOSIS

´ the most frequent symptom is an unpleasant vaginal odor, which patients describe as musty or fishy odor à often stronger following intercourse, when the alkaline semen results in a release of aromatic amines. ´ vaginal discharge associated with bacterial vaginosis is thin and gray-white. ´ Speculum examination reveals that the discharge is mildly adherent to the vaginal walls ´ the four criteria (AMSEL’s CRITERIA) for the diagnosis of bacterial vaginosis are ´ (1) a homogeneous vaginal discharge is present; ´ (2) the vaginal discharge has a pH of 4.5 or higher; ´ (3) the vaginal discharge has an amine-like odor when mixed with potassium hydroxide (whiff test);

´ (4) a wet smear of the vaginal discharge demonstrates clue cells more than 20% of the number of the vaginal epithelial cells. *For the clinician, three our of four criteria are sufficient for a presumptive diagnosis. If available, Gram staining of vaginal secretion is an excellent diagnostic method. 540 Part IIIBACTERIAL GENERAL GYNECOLOGY VAGINOSIS

´ Treament: Table 23.7 Centers for Disease Control and Prevention Recommendations for Treatment of Acute Vaginitis (2015) Disease Drug Dose Cost† Bacterial vaginosis* Metronidazole (Flagyl) 500 mg PO, bid for 7 days† $ Tinidazole 2-g dose PO daily for 2 days $$$ Tinidazole 1-g dose PO daily for 5 days $$$ 0.75% metronidazole gel (Metrogel) One 5-g application intravaginally daily for 5 days‡ $$$ 2% clindamycin cream (Cleocin vaginal) One 5-g application intravaginally every night for 7 days $$$ Clindamycin 300 mg PO, bid for 7 days $ Clindamycin ovules 100 mg intravaginally every night for 3 days $$ Vulvovaginal Candidiasis, Uncomplicated Intravaginal therapy‡ § Azoles 2% butoconazole cream (Mycelex-3) 5 g/day for 4 days§ $$ 2% sustained-release butoconazole cream One 5-g dose $$$ ´ Recurrent bacterial(Gynazole) vaginosis (three or more episodes in the previous year): 10 1% clotrimazole cream (Mycelex-7) 5 g for 7-14 days§ $ days vaginalClotrimazole metronidazole, (Gyne-Lotrimin 3) followed by twiceTwo 100-mg- weekly vaginal tablets/dayuse of 0.75% for 3 days; one 500-mg $ metronidazole gel for 16 weeks vaginal tablet $ 2% miconazole cream 5 g/day for 7 days§ $$ ´ ConcurrentMiconazole treatment (Monistat-7) of the male partnerOne is not100-mg recommended vaginal suppository/day at forthis 7 days time.§ $$ Miconazole (Monistat-3) One 200-mg vaginal suppository/day for 3 days $$ § Comprehensive GynecologyMiconazole 7th edition, (Monistat-1)2017 (Lobo RA, Gershenson DM, LentzOne GM, 1200-mg Valea FA vaginaleditors); suppository chapter 23, Genital tract infections 6.5% tioconazole ointment (Monistat 1-day) One 5-g dose§ $ 0.4% terconazole cream (Terazol 7) 5 g/day for 7 days $$$ 0.8% terconazole cream (Terazol 3) 5 g/day for 3 days $$ Terconazole vaginal One 80-mg vaginal suppository/day for 3 days $$$ Oral therapy Fluconazole (Diflucan) One 150-mg dose PO $

Vulvovaginal Candidiasis, Complicated†‖ Intravaginal therapy‡ Azole 7-14 days $$ Oral therapy¶ Fluconazole (Diflucan) Two 150-mg doses PO, 72 hr apart $$$ Trichomoniasis Metronidazole (Flagyl) One 2-g dose PO, 500 mg orally bid for 7 days $ Tinidazole (Tindamax) One 2-g dose PO** $$

Modified from Eckert LO. Clinical practice: acute vulvovaginitis. N Engl J Med. 2006;355(12):1244-1252. Bid, Twice per day. *†Oral therapy is recommended for pregnant women. †‡Drug may cause gastrointestinal upset in 5% to 10% of patients; a disulfiram reaction is possible; alcohol should be avoided for 24 hr afer ingestion. ‡§Vaginal treatments cause local vaginal irritation in 2% to 5% of patients. §This agent is available over the counter. ‖Complicated vulvovaginitis refers to disease in women who are pregnant, women who have uncontrolled diabetes, women who are immunocompromised, or women who have severe symptoms, non-Candida albicans candidiasis, or recurrent episodes (four or more/year). ¶Oral therapy is not recommended for pregnant women. **Drug may cause gastrointestinal upset in 2% to 5% of patients; disulfiram reaction is possible; alcohol should be avoided 72 hr afer ingestion.

TRICHOMONAS VAGINAL INFECTION studies have established that successful vaginal infection depends Trichomoniasis is caused by the anaerobic fagellated proto- on the deposition of an inoculum of several thousand organisms. zoon, T. vaginalis (Fig. 23.17), a unicellular organism that is Hence, it is unlikely that infection may be related to exposure normally fusiform in shape. Tree to fve fagella extend from from infected towels or swimming pools. one end of the organism and provide active movement of the Trichomonas produces a wide variety of patterns of vaginal protozoon. infection. Te primary symptom of Trichomonas vaginal infec- It is estimated that there are 5 million new cases of trichomo- tion is profuse vaginal discharge. Patients often complain that niasis annually in the United States. Te prevalence of the disease the copious discharge makes them feel “wet.” Approximately remains high, despite the availability of efective treatments since the 50% of symptomatic women also detect an abnormal vaginal early 1960s. Trichomonas vaginal infection is the cause of acute vagi- odor and experience vulvar pruritus; dysuria is a symptom in nitis in 5% to 50% of cases, depending on the population studied, approximately one of fve women with symptomatic Tricho- and is the most prevalent nonviral, nonchlamydial STI of women. monas infection. Women with chronic infection may have a Tis infection is a highly contagious STI; following a single malodorous discharge as their only complaint. sexual contact, at least two thirds of male and female sexual Many women with Trichomonas are symptom free. In one partners become infected. Te are isolated from 30% study of women with positive cultures, only one out of two to 40% of male partners of women with a positive culture and women had symptoms of abnormal vaginal discharge, and only approximately 85% of female partners of a male with a positive one out of six women complained of vulvar pruritus. Positive culture. Te incubation period is 4 to 28 days. Trichomonas is a wet smears or cultures for Trichomonas are reported in 3% to hardy organism and will survive for up to 24 hours on a wet towel 10% of asymptomatic gynecology patients, with a much higher and up to 6 hours on a moist surface. However, experimental percentage being found in women attending an STI clinic.

Obstetrics & Gynecology Books Full TRICHOMONAS VAGINAL INFECTION

´ caused by the anaerobic flagellated protozoon, T. vaginalis ´ thiis infection is a highly contagious STI; ´ Trichomonas is a hardy organism and will survive for up to 24 hours on a wet towel and up to 6 hours on a moist surface. ´ primary symptom of Trichomonas vaginal infection is profuse/copious vaginal discharge. ´ the classic discharge of Trichomonas infection is termed frothy (with bubbles) and often has an unpleasant odor. ´ the classic sign of a strawberry appearance of the upper vagina and cervix is rare and is noted in less than 10% of women. ´ Previously, culture was considered the gold standard to detect T. vaginalis, and wet prep was the most commonly performed diagnostic test ´ Nucleic acid amplification tests (NAATs) are 3-5x times more sensitive than wet prep. NAAT can be performed on vaginal secretions or urine.

Comprehensive Gynecology 7th edition, 2017 (Lobo RA, Gershenson DM, Lentz GM, Valea FA editors); chapter 23, Genital tract infections TRICHOMONAS VAGINAL INFECTION

´ Nitroimidazoles are the only class of drugs recommended for treatment of Trichomonas vaginitis. ´ A single oral dose (2 g) of metronidazole or tinidazole is recommended. ´ An alternate regimen is metronidazole, 500 mg orally, twice daily for 7 days. ´ Metronidazole is safe in all trimesters of pregnancy. Patients should be warned that nitroimidazoles inhibit ethanol metabolism. Women should avoid alcohol for 24 hours after metronidazole and 72 hours after tinidazole therapy to avoid a disulfiram-like reaction. ´ Topical therapy for Trichomonas vaginitis is not recommended because it does not eliminate disease reservoirs in Bartholin and Skene glands.

Comprehensive Gynecology 7th edition, 2017 (Lobo RA, Gershenson DM, Lentz GM, Valea FA editors); chapter 23, Genital tract infections CANDIDA VAGINITIS

´ produced by a ubiquitous, airborne, gram-positive fungus. ´ more than 90% of cases are caused by Candida albicans ´ When the ecosystem of the vagina is disturbed, C. albicans can become an opportunistic pathogen. ´ Hormonal factors, depressed cell-mediated immunity, and antibiotic use are the 3 most important factors that alter the vaginal ecosystem. ´ hormonal changes associated with pregnancy and menstruation favor growth of the fungus. ´ the prevalence of Candida vaginitis increases throughout pregnancy, probably as a result of the high estrogen levels. ´ Lactobacilli inhibit the growth of fungi in the vagina. therefore when the relative concentration of lactobacilli declines, rapid overgrowth of Candida spp. occurs.

Comprehensive Gynecology 7th edition, 2017 (Lobo RA, Gershenson DM, Lentz GM, Valea FA editors); chapter 23, Genital tract infections CANDIDA VAGINITIS

´ Broad-spectrum antibiotics, especially those that destroy lactobacilli (e.g., penicillin, tetracycline, cephalosporins), are notorious for precipitating acute episodes of C. albicans vaginitis. ´ the most important host factor is depressed cell- mediated immunity (Women who take exogenous corticosteroids and women with AIDS ) ´ the greatest enigma of this condition is the recurrence rate after an apparent cure, varying from 20% to 80%. ´ Approximately 3% to 5% of these women experience recurrent vulvovaginal candidiasis (RVVC) à four or more documented episodes in 1 year.

Comprehensive Gynecology 7th edition, 2017 (Lobo RA, Gershenson DM, Lentz GM, Valea FA editors); chapter 23, Genital tract infections CANDIDA VAGINITIS

´ Pruritus is the predominant symptom ´ the vaginal discharge is white or whitish gray, highly viscous, and described as granular or occular, with no odor. ´ During speculum examination, a cottage cheese–type discharge is often visualized, with adherent clumps and plaques (thrush patches) attached to the vaginal walls. ´ e vaginal pH associated with this infection is below 4.5, in contrast to bacterial vaginosis Source: Loyola University Medical Education Network and Trichomonas vaginitis, which are associated with an elevated pH.

Comprehensive Gynecology 7th edition, 2017 (Lobo RA, Gershenson DM, Lentz GM, Valea FA editors); chapter 23, Genital tract infections CANDIDA VAGINITIS

´ diagnosis is established by obtaining a wet 23 Genital Tract Infections 543 smear of vaginal secretion and mixing this with 10% to 20% potassium hydroxide Box 23.3 Classification of Vulvovaginal Candidiasis (VVC) ´ alkali rapidly lyses red blood cells and Uncomplicated VVC Complicated VVC ö Sporadic or infrequent ö Recurrent vulvovaginal inflammatory cells. vulvovaginal candidiasis candidiasis and or ´ Active disease is associated with lamentous ö Mild to moderate vulvovaginal ö Severe vulvovaginal candidiasis candidiasis forms, mycelia, or pseudohyphae, rather than and or spores. ö Likely to be C. albicans ö Non-albicans candidiasis and or › Efe`ddlefZfdgifd`j\[ ö Women with uncontrolled ´ vaginal culture for Candida is particularly women diabetes, debilitation, or useful when a wet mount is negative for immunosuppression Modified from Workowski KA, Bolan GA, Centers for Disease Control and Preven- hyphae, but the patients have symptoms and tion. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep. 2015;64(RR-03):1-137. discharge or other signs suggestive of vul- Figure 23.20 Microscopic appearance of vaginal smear in a case vovaginal candidiasis on examination. of vaginal candidiasis (potassium hydroxide preparation, yeast cells and pseudomycelia; × 320). (From Merkus JM, Bisschop MP, vulvovaginal candidiasis, topical antifungal agents are typically Stolte LA. The proper nature of vaginal candidosis and the problem used for 1 to 3 days, or a single oral dose of fuconazole. Patient ´ Fungal culture may also be useful for women of recurrence. Obstet Gynecol Surv. 1985;40:493-504.) preference, response to prior therapy, and cost should guide the choice of therapy (Workowski, 2015). who have recently treated themselves with For patients with complicated vaginitis, topical azoles are rec- an antifungal agent detect C. albicans on a wet mount is 80% when semiquantitative ommended for 7 to 14 days. If using oral therapy, a second dose culture growth is 3 to 4+, but only 20% when culture growth is of fuconazole (150 mg) given 72 hours after the frst dose is 2+. Hence, a negative smear does not exclude Candida vulvovag- recommended. initis. Te diagnosis can be established by culture with Nicker- In women with RVVC, the resolution of symptoms typically son or Sabouraud medium. Tese cultures will become positive requires longer duration of therapy. Seven to 14 days of topical in 24 to 72 hours. Vaginal culture for Candida is particularly therapy or three doses of oral fuconazole 3 days apart (e.g., days useful when a wet mount is negative for hyphae, but the patients 1, 4, and 7) are options. After this initial treatment, maintenance have symptoms and discharge or other signs suggestive of vul- therapy will help prevent recurrence of symptoms. Oral fucon- vovaginal candidiasis on examination. Fungal culture may also azole (e.g., 100-, 150-, or 200-mg dose) weekly for 6 months is be useful for women who have recently treated themselves with typically frst-line treatment. However, topical treatments used an antifungal agent; up to 90% have a negative culture within intermittently as a maintenance regimen may be considered. 1 week after treatment. It should be stressed that obtaining a Women with recurrent vulvovaginitis should receive a vaginal vaginal culture for bacteria is not useful because anaerobes, coli- fungal culture to determine species and sensitivities. forms, and G. vaginalis all are part of normal vaginal fora. Te Infections with Candida spp. other than C. albicans are often diferential diagnosis includes other common causes of vaginitis, azole resistant. However, one study of terconazole for non–C. such as bacterial vaginosis, Trichomonas vaginitis, and atrophic albicans fungal vaginitis resulted in a mycologic cure in 56% of vaginitis. Also, one should consider noninfectious conditions patients and a symptomatic cure in 44% of women. Vaginal boric such as allergic reactions, contact dermatitis, chemical irritants, acid capsules (600 mg in 0 gelatin capsules) are another option. and rare diseases such as lichen planus. In one study, treatment for a minimum of 14 days resulted in a Te over-the-counter (OTC) availability of vaginal antifun- symptomatic cure rate of 70% for women with non–C. albicans gal therapy makes self-treatment an option for many women. infection. Boric acid inhibits fungal cell wall growth. It may also However, it must be recognized that symptoms suggestive of be used for suppression in women with recurrent vulvovaginal uncomplicated vulvovaginal candidiasis may refect an alterna- candidiasis. Following 10 days of therapy, one 600-mg capsule tive diagnosis. One study of women seen at a clinic for STIs intravaginally twice weekly for 4 to 6 months decreases symp- found that self-treatment of the symptoms listed on the pack- tomatic recurrences. Boric acid is toxic if ingested, so it should age insert of an OTC medication for candidiasis would correctly be stored in a safe manner (Sobel, 1995, 2001, 2003). treat only 28% of patients; 53% had bacterial vaginosis, infec- Studies of alternative therapies for vulvovaginal candidiasis tion with T. vaginalis, , or chlamydia. In another study (such as oral or vaginal Lactobacillus, garlic, or diet alterations involving women purchasing OTC antifungal therapy, only such as yogurt ingestion) do not show efcacy. A summary of 34% had vulvovaginal candidiasis and no other vaginal infec- diagnostic tools for determining the cause of vaginitis and a list tion. If a woman chooses self-treatment, she should be advised treatment options are provided in Tables 23.6 and 23.7. to come in for examination if the symptoms are not eliminated with a single course of OTC therapy. For treatment of vulvovaginal candidiasis, the CDC recom- TOXIC SHOCK SYNDROME mends placing the woman into an uncomplicated or compli- cated category to guide treatment (Box 23.3). A number of Toxic shock syndrome (TSS) is an acute febrile illness produced azole vaginal preparations and a single oral agent, fuconazole, by a bacterial exotoxin, with a fulminating downhill course are approved for treatment. In patients with uncomplicated involving dysfunction of multiple organ systems. Te cardinal

Obstetrics & Gynecology Books Full 23 Genital Tract Infections 543

CANDIDA VAGINITIS Box 23.3 Classification of Vulvovaginal Candidiasis (VVC) Uncomplicated VVC Complicated VVC

ö Sporadic or infrequent ö Recurrent vulvovaginal vulvovaginal candidiasis candidiasis q Treatment: CDC recommends placing and or ö Mild to moderate vulvovaginal ö Severe vulvovaginal the woman into an uncomplicated or candidiasis candidiasis complicated category to guide and or treatment ö Likely to be C. albicans ö Non-albicans candidiasis and or › Efe`ddlefZfdgifd`j\[ ö Women with uncontrolled women diabetes, debilitation, or immunosuppression Modified from Workowski KA, Bolan GA, Centers for Disease Control and Preven- ´ A number of azole vaginal preparationstion. and Sexually a transmitted single diseases oral treatmentagent, guidelines, 2015. MMWR Recomm fluconazole, are approved for treatment.Rep. 2015;64(RR-03):1-137. Figure 23.20 Microscopic appearance of vaginal smear in a case of vaginal´ In candidiasis patients (potassium with hydroxide uncomplicated preparation, yeast vulvovaginal candidiasis, topical antifungal cells andagents pseudomycelia; are × 320).typically (From Merkus used JM, forBisschop 1 to MP, 3 days,vulvovaginal or a single candidiasis, oral dosetopical antifungalof fluconazole. agents are typically Stolte LA. The proper nature of vaginal candidosis and the problem used for 1 to 3 days, or a single oral dose of fuconazole. Patient of recurrence.´ For patientsObstet Gynecol withSurv. 1985;40:493-504.) complicated vaginitis, preference,topical responseazoles to are prior recommendedtherapy, and cost should for guide the 7 to 14 days. If using oral therapy, a secondchoice ofdose therapy of ( Workowski,fluconazole 2015). (150 mg) given 72 hours after the first dose is recommended.For patients with complicated vaginitis, topical azoles are rec- detect C. albicans on a wet mount is 80% when semiquantitative ommended for 7 to 14 days. If using oral therapy, a second dose culture growth is 3 to 4+, but only 20% when culture growth is of fuconazole (150 mg) given 72 hours after the frst dose is Comprehensive Gynecology 7th edition, 2017 (Lobo RA, Gershenson DM, Lentz GM, Valea FA editors); chapter 23, Genital tract infections 2+. Hence, a negative smear does not exclude Candida vulvovag- recommended. initis. Te diagnosis can be established by culture with Nicker- In women with RVVC, the resolution of symptoms typically son or Sabouraud medium. Tese cultures will become positive requires longer duration of therapy. Seven to 14 days of topical in 24 to 72 hours. Vaginal culture for Candida is particularly therapy or three doses of oral fuconazole 3 days apart (e.g., days useful when a wet mount is negative for hyphae, but the patients 1, 4, and 7) are options. After this initial treatment, maintenance have symptoms and discharge or other signs suggestive of vul- therapy will help prevent recurrence of symptoms. Oral fucon- vovaginal candidiasis on examination. Fungal culture may also azole (e.g., 100-, 150-, or 200-mg dose) weekly for 6 months is be useful for women who have recently treated themselves with typically frst-line treatment. However, topical treatments used an antifungal agent; up to 90% have a negative culture within intermittently as a maintenance regimen may be considered. 1 week after treatment. It should be stressed that obtaining a Women with recurrent vulvovaginitis should receive a vaginal vaginal culture for bacteria is not useful because anaerobes, coli- fungal culture to determine species and sensitivities. forms, and G. vaginalis all are part of normal vaginal fora. Te Infections with Candida spp. other than C. albicans are often diferential diagnosis includes other common causes of vaginitis, azole resistant. However, one study of terconazole for non–C. such as bacterial vaginosis, Trichomonas vaginitis, and atrophic albicans fungal vaginitis resulted in a mycologic cure in 56% of vaginitis. Also, one should consider noninfectious conditions patients and a symptomatic cure in 44% of women. Vaginal boric such as allergic reactions, contact dermatitis, chemical irritants, acid capsules (600 mg in 0 gelatin capsules) are another option. and rare diseases such as lichen planus. In one study, treatment for a minimum of 14 days resulted in a Te over-the-counter (OTC) availability of vaginal antifun- symptomatic cure rate of 70% for women with non–C. albicans gal therapy makes self-treatment an option for many women. infection. Boric acid inhibits fungal cell wall growth. It may also However, it must be recognized that symptoms suggestive of be used for suppression in women with recurrent vulvovaginal uncomplicated vulvovaginal candidiasis may refect an alterna- candidiasis. Following 10 days of therapy, one 600-mg capsule tive diagnosis. One study of women seen at a clinic for STIs intravaginally twice weekly for 4 to 6 months decreases symp- found that self-treatment of the symptoms listed on the pack- tomatic recurrences. Boric acid is toxic if ingested, so it should age insert of an OTC medication for candidiasis would correctly be stored in a safe manner (Sobel, 1995, 2001, 2003). treat only 28% of patients; 53% had bacterial vaginosis, infec- Studies of alternative therapies for vulvovaginal candidiasis tion with T. vaginalis, gonorrhea, or chlamydia. In another study (such as oral or vaginal Lactobacillus, garlic, or diet alterations involving women purchasing OTC antifungal therapy, only such as yogurt ingestion) do not show efcacy. A summary of 34% had vulvovaginal candidiasis and no other vaginal infec- diagnostic tools for determining the cause of vaginitis and a list tion. If a woman chooses self-treatment, she should be advised treatment options are provided in Tables 23.6 and 23.7. to come in for examination if the symptoms are not eliminated with a single course of OTC therapy. For treatment of vulvovaginal candidiasis, the CDC recom- TOXIC SHOCK SYNDROME mends placing the woman into an uncomplicated or compli- cated category to guide treatment (Box 23.3). A number of Toxic shock syndrome (TSS) is an acute febrile illness produced azole vaginal preparations and a single oral agent, fuconazole, by a bacterial exotoxin, with a fulminating downhill course are approved for treatment. In patients with uncomplicated involving dysfunction of multiple organ systems. Te cardinal

Obstetrics & Gynecology Books Full CANDIDA VAGINITIS

´ In women with RVVC, the resolution of symptoms typically requires longer duration of therapy. ´ 7 – 14 days of topical therapy or three doses of oral fluconazole 3 days apart (e.g., days 1, 4, and 7) are options. ´ After this initial treatment, maintenance therapy will help prevent recurrence of symptoms. ´ Oral fluconazole (e.g., 100-, 150-, or 200-mg dose) weekly for 6 months is typically first-line treatment.

Comprehensive Gynecology 7th edition, 2017 (Lobo RA, Gershenson DM, Lentz GM, Valea FA editors); chapter 23, Genital tract infections 23 Genital Tract Infections 539

Table 23.6 Diagnostic Tests Available for Vaginitis Test Sensitivity (%) Specificity (%) Comments Bacterial Vaginosis pH >4.5 97 64 Amsel’s criteria 92 77 Must meet three of four clinical criteria (pH >4.5, thin watery discharge, >20% clue cells, positive whif test), but similar results achieved if two of four criteria meet Nugent criteria; Gram stain morphology score (1-10) based on lactobacilli and other morphotypes; score of 1-3 indicates normal flora, score of 7-10 bacterial vaginosis; high interobserver reproducibility Pap smear 49 93 Point-of-care tests QuickVue Advance, pH + amines 89 96 Positive if pH >4.7 QuickVue Advance, G. vaginalis 91 >95 Tests for proline iminopeptidase activity in vaginal fluid; if used when pH >4.5, sensitivity is 95% and specificity is 99% OSOM BV blue 90 <95 Tests for vaginal sialidase activity Candida Wet mount Overall 50 97 Growth of 3-4 + on culture 85 C. albicans a commensal agent in 15%-20% of women Growth of 1 + on culture 23 pH ≤4.5 Usual If symptoms present, pH may be elevated if mixed infection with bacterial vaginosis or T. vaginalis present Pap smear 25 72 Wet mount 45-60 95 Increased visibility of microorganisms with a higher burden of infection Culture 85-90 >95 pH >4.5 56 50 Pap smear 92 61 False-positive rate of 8% for standard Pap test and 4% for liquid-based cytologic test Point-of-care test: OSOM 83 98.8 10 min required to perform tests for T. vaginalis antigens

From Eckert LO. Clinical practice: acute vulvovaginitis. N Engl J Med. 2006;355(12):1244-1252. Comprehensive Gynecology 7th edition, 2017 (Lobo RA, Gershenson DM, Lentz GM, Valea FA editors); chapter 23, Genital tract infections Because there are no efective means of replacing lactobacilli, the treatment for bacterial vaginosis is to decrease anaerobes with antibiotic therapy and hope the woman will then regenerate her own lactobacilli. Table 23.7 provides treatment options. Cure rates are comparable; the agent used should depend on the woman’s preference and cost factors. Treatment results in an 80% symp- tomatic and 70% microbiologic cure at 1 month. Single-dose oral therapy of 2 g of metronidazole is no longer recommended because of high failure rates. alternative regimens include the fol- lowing: tinidazole, 2 g orally for 3 days or 1 g orally for 5 days; clindamycin, 300 mg orally, twice daily for 7 days; and clindamy- cin ovules, 100 mg intravaginally, once at bedtime for 3 days. Recurrent bacterial vaginosis (three or more episodes in the pre- vious year) is a common clinical problem. One double-blind, ran- domized, placebo-controlled trial demonstrated that after 10 days Figure 23.16 Vaginal epithelial cells from woman with bacterial of daily induction therapy with vaginal metronidazole, the twice- vaginosis. These are typical clue cells, heavily covered by coccobacilli, weekly use of 0.75% metronidazole gel for 16 weeks maintains a with loss of distinct cell margins (× 400). (From Holmes KK. Lower clinical cure in 75% of patients at 16 weeks and 50% by 28 weeks. genital tract infections in women: cystitis/, vulvovaginitis, Concurrent treatment of the male partner is not recom- and . In: Holmes KK, Mårdh PA, Sparling PF, et al, eds. mended at this time. Alternative therapies such as the use of oral Sexually Transmitted Diseases. New York: McGraw-Hill; 1984.) or vaginal Lactobacillus are not efcacious.

Obstetrics & Gynecology Books Full TOXIC SHOCK SYNDROME

´ Toxic shock syndrome (TSS) is an acute febrile illness produced by a bacterial exotoxin, with a fulminating downhill course involving dysfunction of multiple organ systems. ´ the cardinal features: abrupt onset and rapidity with which the clinical signs and symptoms may present and progress. ´ A woman with TSS may develop a rapid onset of hypotension associated with multiorgan system failure. ´ S. aureus was isolated from the vagina in more than 90% of these cases. ´ Nonmenstrual TSS may be a sequelae of focal staphylococcal infection of the skin and subcutaneous tissue, often following a surgical procedure.

Comprehensive Gynecology 7th edition, 2017 (Lobo RA, Gershenson DM, Lentz GM, Valea FA editors); chapter 23, Genital tract infections TOXIC SHOCK SYNDROME

´ 3 requirements for the development of classic TSS: ´ (1) the woman must be colonized or infected with S. aureus ´ (2) the bacteria must produce TSS toxin 1 (TSST-1) or related toxins ´ (3) the toxins must have a route of entry into the systemic circulation. ´ signs and symptoms of TSS are produced by the exotoxin named toxin 1. ´ gynecologists should have a high index of suspicion for TSS in a woman who has an unexplained fever and a rash during or immediately fol lowing her menstrual period. ´ the the patient experiences an abrupt onset of a high temperature associated with headache, myalgia, sore throat, vomiting, diarrhea, generalized skin rash, and often hypotension.

Comprehensive Gynecology 7th edition, 2017 (Lobo RA, Gershenson DM, Lentz GM, Valea FA editors); chapter 23, Genital tract infections 23 Genital Tract Infections 545

Box 23.4 Case Definition of Toxic Shock Syndrome even in the absence of a positive S. aureus culture. In patients with TSS caused by methicillin-resistant S. aureus (MRSA), 1. Fever (temperature 38.9° C [102° F]) clindamycin plus vancomycin (30 mg/kg/day IV in two 2. Rash characterized by difuse macular erythroderma divided doses) or linezolid (600 mg oral or IV every 12 hours) 3. Desquamation occurring 1-2 wk afer onset of illness (in survivors) is used. If the diagnosis is questionable, it is best to include 4. Hypotension (systolic blood pressure ≤90 mm Hg in adults) or orthostatic syncope an aminoglycoside to obtain coverage for possible gram-neg- 5. Involvement of three or more of the following organ systems: ative sepsis. Antibiotic therapy probably has little efect on a. Gastrointestinal (vomiting or diarrhea at onset of illness) the course of an individual episode of TSS. However, if the b. Muscular (myalgia or creatine phosphokinase level twice underlying cause of toxic shock syndrome is a skin infection, normal) the infected site should be drained and débrided. Treatment c. Mucous membrane (vaginal, oropharyngeal, or conjunctival with mupirocin to decrease colonization is recommended, hyperemia) applying half of the ointment from a single-use tube into one d. Renal (BUN or creatinine level ≥ twice normal or ≥5 WBCs/ nostril and the other half into the other nostril twice daily HPF in absence of UTI) for 5 days. e. Hepatic (total bilirubin, SGOT, or SGPT twice normal level) In summary, the treatment of TSS depends on the severity of f. Hematologic (platelets ≤100,000/mm3) g. Central nervous system (disorientation or alteration in con- involvement of individual organ systems. Not all patients develop sciousness without focal neurologic signs when fever and a temperature higher than 38.9° C and hypotension. Tus clini- hypotension are absent) cians should be aware of the forme fruste manifestations of the h. Cardiopulmonary (adult respiratory distress syndrome, pul- syndrome. Te foundation of treatment of the disease is prompt monary edema, new onset of second- or third-degree heart and aggressive management because of the rapidity with which block, myocarditis) the disease may progress. 6. Negative throat and cerebrospinal fluid cultures (a positive It is possible to decrease the incidence of TSS by a change in blood culture for Staphylococcus aureus does not exclude a case) the use of catamenial products. Women should be encouraged 7. Negative serologic test results for Rocky Mountain spotted to change tampons every 4 to 6 hours. Te intermittent use of fever, leptospirosis, rubeola external pads is also good preventive medicine. Women will usu- From Centers for Disease Control (CDC). Toxic-shock syndrome, United States, ally accept the recommendation to wear external pads during 1970-1982. MMWR Morb Mortal Wkly Rep. 1982;31:201. BUN, Blood urea nitrogen; HPF, high-powered field; SGOT, serum glutamic-oxa- sleep. Te incidence of TSS has decreased dramatically with the loacetic transaminase; SGPT, serum glutamic-pyruvic transaminase; UTI, urinary removal of super-absorbing tampons from the market. A study tract infection; WBC, white blood cell count. by Tierno and Hanna reported that all-cotton tampons are the safest choice to avoid menstrual TSS. Finally, there are cases of streptococcal toxic shock–like syn- Comprehensive GynecologyBox 7th edition,23.5 Laboratory 2017 (Lobo RA,Abnormalities Gershenson DM, in EarlyLentz GM,Toxic Valea ShockFA editors); chapter 23, Genital tract infections Syndrome dromes that are secondary to life-threatening infections with group A streptococcus (Streptococcus pyogenes). Several difer- Present in >85% of patients ent exotoxins have been identifed, and M types 1 and 3 are Coagulase-positive staphylococci in cervix or vagina the two most common serotypes. In gynecology, most of these Immature and mature polymorphonuclear cells >90% of WBCs cases involve massive subcutaneous postoperative infections. Total lymphocyte count <650/mm3 Total serum protein level <5.6 mg/dL One of the most distinguishing characteristics of a necrotiz- Serum albumin level <3.1 g/dL ing skin infection is the intense localized pain in the involved Serum calcium level <7.8 mg/dL area. Older women and women who are diabetic or immu- Serum creatinine clearance >1 mg/dL nocompromised are at much greater risk to develop invasive Serum bilirubin level >1.5 mg/dL streptococcal infection and streptococcal toxic shock–like syn- Serum cholesterol level ≤120 mg/dL drome. Te mortality rate is approximately 30% when TSS is Prothrombin time >12 seconds secondary to group A streptococcal infections (Al-ajmi, 2012; Present in >70% of patients LeRiche, 2012). Platelet count <150,000/mm3 Pyuria >5 WBCs/HPF Proteinuria ≥2+ BUN >20 mg/dL CERVICITIS Aspartate aminotransferase (formerly SGOT) >41 U/L Cervicitis, an infammatory process in the cervical epithelium From Chesney PJ, Davis JP, Purdy WK, et al. Clinical manifestations of toxic shock and stroma, can be associated with trauma, infammatory sys- syndrome. JAMA. 1981;246:746. BUN, Blood urea nitrogen; HPF, high-powered field; SGOT, serum glutamic- temic disease, neoplasia, and infection. Although it is clinically oxaloacetic transaminase; WBCs, white blood cells. important to consider all causes of infammation, this section Results were available for at least 18 patients per category with the following focuses on infectious origins. exceptions: cervicovaginal cultures (12 patients), cholesterol level (15 patients), Te cervix acts as a barrier between the abundant bacterial and prothrombin time (14 patients). fora of the vagina and the bacteriologically sterile endometrial cavity and oviducts. Cervical mucus is much more than a sim- Women with TSS caused by methicillin-susceptible S. ple physical barrier; it exerts a bacteriostatic efect. Mucus may aureus should be treated with clindamycin, 600 mg IV every also act as a competitive inhibitor with bacteria for receptors on 8 hours, plus nafcillin or oxacillin, 2 g IV every 4 hours. Most the endocervical epithelial cells. Cervical mucus also contains experts recommend a 1- to 2-week course of therapy with an antibodies and infammatory cells that are active against various antistaphylococcal agent such as clindamycin or dicloxacillin, sexually transmitted organisms.

Obstetrics & Gynecology Books Full TOXIC SHOCK SYNDROME

´ the most characteristic manifestations of TSS are the skin changes. ´ During the first 48 hours, the skin rash appears similar to intense sunburn. ´ During the next few days, the erythema will become more macular and resemble a drug-related rash. ´ From days 12 to 15 of the illness, there is a fine, flaky desquamation of skin over the face and trunk, with sloughing of the entire skin thickness of the palms and soles.

´ During pelvic examination, patients complain of tenderness of the external genitalia and vagina.

Comprehensive Gynecology 7th edition, 2017 (Lobo RA, Gershenson DM, Lentz GM, Valea FA editors); chapter 23, Genital tract infections 23 Genital Tract Infections 545

Box 23.4 Case Definition of Toxic Shock Syndrome even in the absence of a positive S. aureus culture. In patients with TSS caused by methicillin-resistant S. aureus (MRSA), 1. Fever (temperature 38.9° C [102° F]) clindamycin plus vancomycin (30 mg/kg/day IV in two 2. Rash characterized by difuse macular erythroderma divided doses) or linezolid (600 mg oral or IV every 12 hours) 3. Desquamation occurring 1-2 wk afer onset of illness (in survivors) is used. If the diagnosis is questionable, it is best to include 4. Hypotension (systolic blood pressure ≤90 mm Hg in adults) or orthostatic syncope an aminoglycoside to obtain coverage for possible gram-neg- 5. Involvement of three or more of the following organ systems: ative sepsis. Antibiotic therapy probably has little efect on a. Gastrointestinal (vomiting or diarrhea at onset of illness) the course of an individual episode of TSS. However, if the b. Muscular (myalgia or creatine phosphokinase level twice underlying cause of toxic shock syndrome is a skin infection, normal) the infected site should be drained and débrided. Treatment c. Mucous membrane (vaginal, oropharyngeal, or conjunctival with mupirocin to decrease colonization is recommended, hyperemia) applying half of the ointment from a single-use tube into one d. Renal (BUN or creatinine level ≥ twice normal or ≥5 WBCs/ nostril and the other half into the other nostril twice daily HPF in absence of UTI) for 5 days. e. Hepatic (total bilirubin, SGOT, or SGPT twice normal level) In summary, the treatment of TSS depends on the severity of f. Hematologic (platelets ≤100,000/mm3) g. Central nervous system (disorientation or alteration in con- involvement of individual organ systems. Not all patients develop sciousness without focal neurologic signs when fever and a temperature higher than 38.9° C and hypotension. Tus clini- hypotension are absent) cians should be aware of the forme fruste manifestations of the h. Cardiopulmonary (adult respiratory distress syndrome, pul- syndrome. Te foundation of treatment of the disease is prompt monary edema, new onset of second- or third-degree heart and aggressive management because of the rapidity with which block, myocarditis) the disease may progress. 6. Negative throat and cerebrospinal fluid cultures (a positive It is possible to decrease the incidence of TSS by a change in blood culture for Staphylococcus aureus does not exclude a case) the use of catamenial products. Women should be encouraged 7. Negative serologic test results for Rocky Mountain spotted to change tampons every 4 to 6 hours. Te intermittent use of fever, leptospirosis, rubeola external pads is also good preventive medicine. Women will usu- From Centers for Disease Control (CDC). Toxic-shock syndrome, United States, ally accept the recommendation to wear external pads during 1970-1982. MMWR Morb Mortal Wkly Rep. 1982;31:201. BUN, Blood urea nitrogen; HPF, high-powered field; SGOT, serum glutamic-oxa- sleep. Te incidence of TSS has decreased dramatically with the loacetic transaminase; SGPT, serum glutamic-pyruvic transaminase; UTI, urinary removal of super-absorbing tampons from the market. A study tract infection; WBC, white blood cell count. by Tierno and Hanna reported that all-cotton tampons are the safest choice to avoid menstrual TSS. Finally, there are cases of streptococcal toxic shock–like syn- Box 23.5 Laboratory Abnormalities in Early Toxic Shock Syndrome dromes that are secondary to life-threatening infections with group A streptococcus (Streptococcus pyogenes). Several difer- Present in >85% of patients ent exotoxins have been identifed, and M types 1 and 3 are Coagulase-positive staphylococci in cervix or vagina the two most common serotypes. In gynecology, most of these Immature and mature polymorphonuclear cells >90% of WBCs cases involve massive subcutaneous postoperative infections. Total lymphocyte count <650/mm3 Total serum protein level <5.6 mg/dL One of the most distinguishing characteristics of a necrotiz- Serum albumin level <3.1 g/dL ing skin infection is the intense localized pain in the involved Serum calcium level <7.8 mg/dL area. Older women and women who are diabetic or immu- Serum creatinine clearance >1 mg/dL nocompromised are at much greater risk to develop invasive Serum bilirubin level >1.5 mg/dL streptococcal infection and streptococcal toxic shock–like syn- Serum cholesterol level ≤120 mg/dL drome. Te mortality rate is approximately 30% when TSS is Prothrombin time >12 seconds secondary to group A streptococcal infections (Al-ajmi, 2012; Present in >70% of patients LeRiche, 2012). Platelet count <150,000/mm3 Pyuria >5 WBCs/HPF Proteinuria ≥2+ BUN >20 mg/dL CERVICITIS Aspartate aminotransferase (formerly SGOT) >41 U/L Cervicitis, an infammatory process in the cervical epithelium From Chesney PJ, Davis JP, Purdy WK, et al. Clinical manifestations of toxic shock and stroma, can be associated with trauma, infammatory sys- syndrome. JAMA. 1981;246:746. BUN, Blood urea nitrogen; HPF, high-powered field; SGOT, serum glutamic- temic disease, neoplasia, and infection. Although it is clinically oxaloacetic transaminase; WBCs, white blood cells. important to consider all causes of infammation, this section Results were available for at least 18 patients per category with the following focuses on infectious origins. exceptions: cervicovaginal cultures (12 patients), cholesterol level (15 patients), Te cervix acts as a barrier between the abundant bacterial and prothrombin time (14 patients). fora of the vagina and the bacteriologically sterile endometrial cavity and oviducts. Cervical mucus is much more than a sim- th Comprehensive GynecologyWomen 7 edition, with2017 (Lobo TSS RA, caused Gershenson byDM, methicillin-susceptible Lentz GM, Valea FA editors); chapterS. 23,ple Genital physical tract barrier; infections it exerts a bacteriostatic efect. Mucus may aureus should be treated with clindamycin, 600 mg IV every also act as a competitive inhibitor with bacteria for receptors on 8 hours, plus nafcillin or oxacillin, 2 g IV every 4 hours. Most the endocervical epithelial cells. Cervical mucus also contains experts recommend a 1- to 2-week course of therapy with an antibodies and infammatory cells that are active against various antistaphylococcal agent such as clindamycin or dicloxacillin, sexually transmitted organisms.

Obstetrics & Gynecology Books Full TOXIC SHOCK SYNDROME

´ the management of a classic case of severe TSS demands an intensive care unit and the skills of an expert in critical care medicine. ´ the first priority is to eliminate the hypotension produced by the exotoxin. ´ Copious amounts of IV fluids are given while pressure and volume dynamics are centrally monitored. ´ Mechanical ventilation is required for women who develop adult respiratory distress syndrome. ´ When the woman is initially admitted to the hospital, it is important to obtain cervical, vaginal, and blood cultures for S. aureus. ´ it is prudent to wash out the vagina with saline or dilute iodine solution to diminish the amount of exotoxin that may be absorbed into the systemic circulation.

Comprehensive Gynecology 7th edition, 2017 (Lobo RA, Gershenson DM, Lentz GM, Valea FA editors); chapter 23, Genital tract infections TOXIC SHOCK SYNDROME

´Treatment: ´ Women with TSS caused by methicillin-susceptible S. aureus should be treated with clindamycin, 600 mg IV every 8 hours, plus nafcillin or oxacillin, 2 g IV every 4 hours. ´ Most experts recommend a 1- to 2-week course of therapy with an antistaphylococcal agent such as clindamycin or dicloxacillin even in the absence of a positive S. aureus culture. ´ In patients with TSS caused by methicillin-resistant S. aureus (MRSA): clindamycin plus vancomycin (30 mg/kg/day IV in two divided doses) or linezolid (600 mg oral or IV every 12 hours) is used. ´ the infected site should be drained and debrided́ . Treatment with mupirocin to decrease colonization is recommended, applying half of the ointment from a single-use tube into one nostril and the other half into the other nostril twice daily for 5 days.

Comprehensive Gynecology 7th edition, 2017 (Lobo RA, Gershenson DM, Lentz GM, Valea FA editors); chapter 23, Genital tract infections CERVICITIS CERVICITIS

´ can be associated with trauma, inflammatory systemic disease, neoplasia, and infection. ´ the cervix (and cervical mucus) acts as a barrier between the abundant bacterial flora of the vagina and the bacteriologically sterile endometrial cavity and oviducts. ´ Cervical infection can be ectocervicitis or endocervicitis. Ectocervicitis can be viral (HSV) or from a severe vaginitis (e.g., strawberry cervix associated with T. vaginalis infection) or C. albicans. ´ Endocervicitis may be secondary to infection with C. trachomatis or N. gonorrhoeae. ´ Infection of the endocervix becomes a major reservoir for sexual and perinatal transmission of pathogenic microorganisms. ´ Primary endocervical infection may result in secondary ascending infections, including pelvic inflammatory disease and perinatal infections of the membranes, amniotic fluid, and parametria. MUCOPURULENT CERVICITIS546 Part III GENERAL GYNECOLOGY

Often, the woman is asymptomatic, even though the cervix is colonized with organisms. Te cervix is a potential reservoir for Neisseria gonorrhoeae, Chlamydia trachomatis, HSV, human papillomavirus, and Mycoplasma spp. Cervical infection can be ectocervicitis or endocervicitis. Ectocervicitis can be viral (HSV) or from a severe vaginitis (e.g., strawberry cervix associ- ´ 2 simple, definitive, objective criteria haveated with T. beenvaginalis infection) developed or C. albicans. Endocervicitis to may be secondary to infection with C. trachomatis or N. gonor- establish mucopurulent cervicitis: rhoeae. Bacterial vaginosis and Mycoplasma genitalium have also been associated with endocervicitis. Infection of the endocervix becomes a major reservoir for sexual and perinatal transmission ´ 1. gross visualization of yellow mucopurulentof pathogenic microorganisms. material Primary endocervical on infection a may result in secondary ascending infections, including pelvic white cotton swab ( infammatory disease and perinatal infections of the membranes, amniotic fuid, and parametria. Te histologic diagnosis of chronic cervicitis is so prevalent ´ 2. presence of 10 or more PMN leukocytesthat it should be considered per themicroscopic norm for parous women of reproductive age. Te histopathology of endocervicitis is charac- field (magnification, × 1000) on Gramterized by- staineda severe infammatory smears reaction in the mucosa and sub- mucosa. Te tissues are infltrated with a large number of PMNs obtained from the endocervix. A and monocytes and, occasionally, there is associated epithelial Figure 23.21 Mucopurulent cervicitis demonstrated by a cotton necrosis. Physiologically, there is a resident population of a small swab test. number of leukocytes in the normal cervix. Tus the emphasis is ´ Symptoms that suggest cervical infectionon a severe includeinfammatory reaction vaginal by a large number of PMNs. Tis section focuses on mucopurulent cervicitis and techniques discharge, deep dyspareunia, and postcoitalto diagnose common bleeding.cervical infections.

´ the physical sign of a cervical infectionMUCOPURULENT is a cervix CERVICITIS that is Te diagnosis of cervicitis continues to rely on symptoms, exam- hypertrophic and edematous. ination, and microscopic evaluation. Two simple, defnitive, objective criteria have been developed to establish mucopurulent cervicitis—gross visualization of yellow mucopurulent material ´ C. trachomatis and N. gonorrhea areonthe a white cottonmost swab (Fig.common 23.21) and the presence cause of 10 or more PMN leukocytes per microscopic feld (magnifcation, × of cervical infection in many women with1000) on Gram-stainedmucopurulent smears obtained from the endocervix. Alternative clinical criteria that may be used are erythema and cervicitis edema in an area of cervical ectopy or associated with bleeding secondary to endocervical ulceration or friability when the endo- Figure 23.22 Patient with C. trachomatis mucopurulent cervicitis th cervical smear is obtained. Women may also report increased Comprehensive Gynecology 7 edition, 2017 (Lobo RA, GershensonvaginalDM, discharge Lentz and intermenstrual GM, Valea vaginal bleeding.FA editors); chapterwith resolution 23, post treatment.Genital tract infections Te prevalence of mucopurulent cervicitis depends on the population being studied. Approximately 30% to 40% of therapy. Te presence of active herpes infection is correlated with women attending clinics for STIs and 8% to 10% of women in ulceration of the ectocervix but not with mucopus. university student health clinics have the condition. More than When mucopurulent cervicitis is clinically diagnosed, empiri- 60% of women with this disease are asymptomatic. Symptoms cal therapy for C. trachomatis is recommended for women at that suggest cervical infection include vaginal discharge, deep increased risk of this common STI (age <25 years, new or mul- dyspareunia, and postcoital bleeding. Te physical sign of a cer- tiple sex partners, unprotected sex). If the prevalence of N. gonor- vical infection is a cervix that is hypertrophic and edematous. rhoeae is more than 5%, concurrent therapy for N. gonorrhoeae is C. trachomatis is the cause of cervical infection in many indicated. Concomitant trichomoniasis should also be treated if women with mucopurulent cervicitis (Fig. 23.22). Depending detected, as should bacterial vaginosis. If presumptive treatment is on the geographic region, gonorrhea is also an important cause deferred, the use of a sensitive nucleic acid test for C. trachomatis of mucopurulent cervicitis. However, most women who have and N. gonorrhoeae is needed. lower reproductive tract infections caused by C. trachomatis or Recommended regimens for presumptive cervicitis therapy N. gonorrhoeae do not have mucopurulent cervicitis. Te corol- include azithromycin, 1 g orally in a single dose, or doxycycline, lary is that most women who have mucopurulent cervicitis are 100 mg orally twice daily for 7 days, adding gonococcal treat- not infected by C. trachomatis or N. gonorrhoeae. Mucopurulent ment if the prevalence is over 5% in the population assessed. cervicitis is present in approximately 40% to 60% of women in Women treated for chlamydia should be instructed to abstain whom no cervical pathogen can be identifed. Tus this condi- from sexual intercourse for 7 days after single-dose therapy or tion often persists following adequate broad-spectrum antibiotic until completion of the 7-day regimen (Workowski, 2015).

Obstetrics & Gynecology Books Full MUCOPURULENT CERVICITIS546 Part III GENERAL GYNECOLOGY

Often, the woman is asymptomatic, even though the cervix is colonized with organisms. Te cervix is a potential reservoir for Neisseria gonorrhoeae, Chlamydia trachomatis, HSV, human ´ Gold standard for diagnosis: NAAT papillomavirus, and Mycoplasma spp. Cervical infection can be ectocervicitis or endocervicitis. Ectocervicitis can be viral (HSV) or from a severe vaginitis (e.g., strawberry cervix associ- ´ When mucopurulent cervicitis is clinicallyated with T. vaginalisdiagnosed, infection) or C. albicans . Endocervicitis may be secondary to infection with C. trachomatis or N. gonor- empirical therapy for C. trachomatisrhoeae. is recommendedBacterial vaginosis and Mycoplasma genitalium have also been associated with endocervicitis. Infection of the endocervix for women at increased risk of this commonbecomes a major reservoir STI for sexual(age and perinatal <25 transmission of pathogenic microorganisms. Primary endocervical infection may result in secondary ascending infections, including pelvic years, new or multiple sex partners, unprotectedinfammatory disease and perinatal infectionssex). of the membranes, amniotic fuid, and parametria. Te histologic diagnosis of chronic cervicitis is so prevalent ´ Recommended regimens for presumptivethat it should be cervicitis considered the norm for parous women of reproductive age. Te histopathology of endocervicitis is charac- therapy include: terized by a severe infammatory reaction in the mucosa and sub- mucosa. Te tissues are infltrated with a large number of PMNs and monocytes and, occasionally, there is associated epithelial Figure 23.21 Mucopurulent cervicitis demonstrated by a cotton ´ azithromycin, 1 g orally in a singlenecrosis. dose Physiologically, there is a resident population of a small swab test. number of leukocytes in the normal cervix. Tus the emphasis is on a severe infammatory reaction by a large number of PMNs. ´ doxycycline, 100 mg orally twice Tdailyis section focuses for on mucopurulent7 days cervicitis and techniques to diagnose common cervical infections. ´ Add gonococcal treatment if the prevalence is over MUCOPURULENT CERVICITIS 5% in the population assessed. Te diagnosis of cervicitis continues to rely on symptoms, exam- ination, and microscopic evaluation. Two simple, defnitive, objective criteria have been developed to establish mucopurulent ´ Women treated for chlamydia shouldcervicitis—gross be instructed visualization of yellow mucopurulent to material on a white cotton swab (Fig. 23.21) and the presence of 10 or abstain from sexual intercourse for 7 moredays PMN leukocytes after per microscopic single feld -(magnifcation, × 1000) on Gram-stained smears obtained from the endocervix. dose therapy or until completion of theAlternative 7 clinical-day criteria thatregimen may be used are erythema and edema in an area of cervical ectopy or associated with bleeding secondary to endocervical ulceration or friability when the endo- cervical smear is obtained. Women may also report increased Figure 23.22 Patient with C. trachomatis mucopurulent cervicitis Comprehensive Gynecology 7th edition, 2017 (Lobo RA, GershensonvaginalDM, discharge Lentz and intermenstrual GM, Valea vaginal bleeding.FA editors); chapterwith resolution 23, post treatment.Genital tract infections Te prevalence of mucopurulent cervicitis depends on the population being studied. Approximately 30% to 40% of therapy. Te presence of active herpes infection is correlated with women attending clinics for STIs and 8% to 10% of women in ulceration of the ectocervix but not with mucopus. university student health clinics have the condition. More than When mucopurulent cervicitis is clinically diagnosed, empiri- 60% of women with this disease are asymptomatic. Symptoms cal therapy for C. trachomatis is recommended for women at that suggest cervical infection include vaginal discharge, deep increased risk of this common STI (age <25 years, new or mul- dyspareunia, and postcoital bleeding. Te physical sign of a cer- tiple sex partners, unprotected sex). If the prevalence of N. gonor- vical infection is a cervix that is hypertrophic and edematous. rhoeae is more than 5%, concurrent therapy for N. gonorrhoeae is C. trachomatis is the cause of cervical infection in many indicated. Concomitant trichomoniasis should also be treated if women with mucopurulent cervicitis (Fig. 23.22). Depending detected, as should bacterial vaginosis. If presumptive treatment is on the geographic region, gonorrhea is also an important cause deferred, the use of a sensitive nucleic acid test for C. trachomatis of mucopurulent cervicitis. However, most women who have and N. gonorrhoeae is needed. lower reproductive tract infections caused by C. trachomatis or Recommended regimens for presumptive cervicitis therapy N. gonorrhoeae do not have mucopurulent cervicitis. Te corol- include azithromycin, 1 g orally in a single dose, or doxycycline, lary is that most women who have mucopurulent cervicitis are 100 mg orally twice daily for 7 days, adding gonococcal treat- not infected by C. trachomatis or N. gonorrhoeae. Mucopurulent ment if the prevalence is over 5% in the population assessed. cervicitis is present in approximately 40% to 60% of women in Women treated for chlamydia should be instructed to abstain whom no cervical pathogen can be identifed. Tus this condi- from sexual intercourse for 7 days after single-dose therapy or tion often persists following adequate broad-spectrum antibiotic until completion of the 7-day regimen (Workowski, 2015).

Obstetrics & Gynecology Books Full 23 Genital Tract Infections 547

Mycoplasma genitalium, which is noncultivable, has been Box 23.6 Centers for Disease Control and Prevention associated in women with mucopurulent cervicitis by DNA Recommended Dual Treatment of Uncomplicated testing. Empiric treatment for M. genitalium in cases of persis- Gonococcal Infections of the Cervix, Urethra, and tent cervicitis after standard treatment may be considered but Rectum in Adults (2014) should be done in consultation with a specialist. Tere is no Cefriaxone, 250 mg IM, single dose FDA-approved diagnostic test for M. genitalium in the United or, if not an option States. Some research laboratories may have PCR-based testing. Cefixime, 400 mg PO, single dose Bacterial vaginosis has also been associated with mucopurulent plus cervicitis; cervicitis resolved with bacterial vaginosis treatment Azithromycin 1 g orally in a single doses, preferably under direct (Workowski, 2015). observation Modified from Workowski KA, Bolan GA, Centers for Disease Control and Preven- DETECTION OF PATHOGENIC23 GenitalCERVICAL Tract Infections tion.547 Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep. 2015;64(RR-03):1-137. BACTERIA Neisseria gonorrhoeae Mycoplasma genitalium, which is noncultivable, has been NucleicBox acid 23.6 ampli Centersfcation for Disease testing (NAAT)Control and of thePrevention urine or vagi- Box 23.7 Recommended Regimens for Treatment of associated in women with mucopurulent cervicitis by DNA nal secretions Recommendedis the most sensitive Dual Treatmentand specif ofc diagnosticUncomplicated tool Chlamydial Infection for identifying gonorrheal infections. Urine tests should be frst testing. Empiric treatment for M. genitalium in cases of persis- Gonococcal Infections of the Cervix, Urethra, and Azithromycin, 1 g PO, single dose* void (either the frst void in morning or at least 1 hour since last tent cervicitis after standard treatment may be considered but Rectum in Adults (2014) or void). Tis technique allows for the sensitive detection of DNA Doxycycline, 100 mg PO bid for 7 days should be done in consultation with a specialist. Tere is no particlesCef riaxone,originating 250 mgfrom IM, the single urethra dose or endocervix, which fall into the vaginal pool and vestibule. Alternative Regimens FDA-approved diagnostic test for M. genitalium in the United or, if not an option Erythromycin base, 500 mg PO qid for 7 days Most women who are colonized with N. gonorrhoeae are States. Some research laboratories may have PCR-based testing. Cefixime, 400 mg PO, single dose or asymptomatic. Terefore it is important to screen women at Bacterial vaginosis has also been associated with mucopurulent plus Erythromycin ethylsuccinate, 800 mg PO qid for 7 days high risk for gonorrheal infection routinely. Screening of high- or cervicitis; cervicitis resolved with bacterial vaginosis treatment risk individualsAzithromycin is 1 theg orally primary in a single modality doses, to preferably control underthe disease. direct Ofloxacin, 300 mg PO bid for 7 days (Workowski, 2015). Gonorrhealobservation NAAT results are over 95% sensitive and specifc. or Antibiotic-resistant gonorrhea culture (GC) is problematic. Levofloxacin, 500 mg PO once daily for 7 days Modified from Workowski KA, Bolan GA, Centers for Disease Control and Preven- CDC STD Treatment Guidelines (2015) recommend dual tion. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Modified from Workowski KA, Bolan GA, Centers for Disease Control and Preven- DETECTION OF PATHOGENIC CERVICAL therapy with ceftriaxone 250 mg once IM and azithromycin 1 g tion. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep. 2015;64(RR-03):1-137. BACTERIA orally in a single dose, preferably under direct observation, for Rep. 2015;64(RR-03):1-137. bid, Twice per day; qid, four times per day. all GC infections (Boxes 23.6 and 23.7). Routine co-treatment * Consider concurrent treatment for gonococcal infection if prevalence of gonor- rhea is high in the patient population under assessment. Neisseria gonorrhoeae using two antimicrobials with diferent mechanisms of action, th Nucleic acid amplifcation testing (NAAT) of the urine or vagi- such Boxas aComprehensive 23.7 cephalosporin Recommended Gynecology plus azithromycin, Regimens 7 edition, for Treatmentmay 2017 slow (Lobo the of RA, selec Gershenson- DM, Lentz GM, Valea FA editors); chapter 23, Genital tract infections nal secretions is the most sensitive and specifc diagnostic tool tion and spreadChlamydial of antibiotic-resistant Infection GC. Based on experience attaches to the columnar epithelium. Hence, vaginal specimens with other microbes that developed antimicrobial resistance rap- should not be collected from women who have had a hyster- for identifying gonorrheal infections. Urine tests should be frst idly, Azithromycin,a theoretic basis 1 g PO, exists single for dose combination* therapy using two ectomy. When a culture is used for diagnosis, C. trachomatis is void (either the frst void in morning or at least 1 hour since last antimicrobialsor with diferent mechanisms of action to improve an obligatory intracellular organism; hence, it is mandatory to void). Tis technique allows for the sensitive detection of DNA treatmentDoxycycline, efcacy 100 and mg potentially PO bid for delay7 days emergence and spread of obtain epithelial cells to maximize the percentage of positive cul- particles originating from the urethra or endocervix, which fall resistance to cephalosporins. Azithromycin is preferred to doxy- tures. A Dacron, rayon, or calcium alginate swab is placed in the cyclineAlternative because ofRegimens the convenience and compliance advantages endocervical canal. It is rotated for 15 to 20 seconds to abrade into the vaginal pool and vestibule. of single-doseErythromycin therapy base, 500 and mg the PO substantially qid for 7 days higher prevalence the columnar epithelium gently. Te Cytobrush, which was Most women who are colonized with N. gonorrhoeae are of gonococcalor resistance to tetracycline than to azithromycin in developed primarily to enhance sampling of endocervical cells asymptomatic. Terefore it is important to screen women at trackedErythromycin isolates. ethylsuccinate, 800 mg PO qid for 7 days for cytology, has been found to be the optimal instrument for high risk for gonorrheal infection routinely. Screening of high- Ifor the woman is asymptomatic, the CDC no longer recom- appropriate sampling for Chlamydia culture as well. Chlamydial mends follow-up testing for a test of cure for lower tract infec- antigen detection is insensitive and nonspecifc compared with risk individuals is the primary modality to control the disease. Ofloxacin, 300 mg PO bid for 7 days tions (uncomplicated gonorrhea). However, studies have shown NAAT and is no longer recommended. Gonorrheal NAAT results are over 95% sensitive and specifc. a highor rate of reinfection, so rescreening patients is prudent. C. trachomatis infection is frequently asymptomatic. Chla- Antibiotic-resistant gonorrhea culture (GC) is problematic. WomenLevofloxacin, with positive 500 mg cultures PO once for daily gonorrhea for 7 days should have a sero- mydial screening programs have been successful at decreasing CDC STD Treatment Guidelines (2015) recommend dual logicModified test for from syphilis Workowski in KA,4 to Bolan 6 weeks, GA, Centers even for though Disease Control patients and withPreven - the prevalence of the disease. Te CDC recommends annual therapy with ceftriaxone 250 mg once IM and azithromycin 1 g incubatingtion. Sexually syphilis transmitted are usually diseases treatmentcured by guidelines, antibiotic 2015. combinations MMWR Recomm screening of all sexually active women 25 years of age or younger of ceftriaxoneRep. 2015;64(RR-03):1-137. and tetracycline. bid, Twice Similarly, per day; qid , four patients times per should day. be and screening of older women with risk factors (e.g., those who orally in a single dose, preferably under direct observation, for ofered informed consent and testing for HIV infection. have a new sex partner or multiple partners). all GC infections (Boxes 23.6 and 23.7). Routine co-treatment * Consider concurrent treatment for gonococcal infection if prevalence of gonor- Itrhea is important is high in the patientto remember population that under N. assessment. gonorrhoeae attaches to For all women with a chlamydial or gonorrheal infection, using two antimicrobials with diferent mechanisms of action, the columnar epithelium, so a vaginal cuf swab in women with partners should be treated. Patients should be instructed to refer such as a cephalosporin plus azithromycin, may slow the selec- prior hysterectomies is not recommended (Workowski, 2015). all sex partners of the past 60 days for evaluation and treatment tion and spread of antibiotic-resistant GC. Based on experience attaches to the columnar epithelium. Hence, vaginal specimens and to avoid sexual intercourse until therapy is completed and Chlamydia trachomatis they and their partner have resolution of symptoms. with other microbes that developed antimicrobial resistance rap- As should with gonorrhea, not be collected the gold from standard women of who techniques have had used a hyster to - If a woman is unsure whether her partner will be treated, idly, a theoretic basis exists for combination therapy using two identifyectomy. C. When trachomatis a culture infection is used is for NAAT. diagnosis, C. trachomatis C. trachomatis also is delivery of antibiotic therapy (by prescription or medication) antimicrobials with diferent mechanisms of action to improve an obligatory intracellular organism; hence, it is mandatory to treatment efcacy and potentially delay emergence and spread of obtain epithelial cells to maximize the percentage of positive cul- resistance to cephalosporins. Azithromycin is preferred to doxy- tures. A Dacron, rayon, or calcium alginate swab is placed in the cycline because of the convenience and compliance advantages endocervical canal. It is rotated for 15 toObstetrics 20 seconds &to Gynecologyabrade Books Full of single-dose therapy and the substantially higher prevalence the columnar epithelium gently. Te Cytobrush, which was of gonococcal resistance to tetracycline than to azithromycin in developed primarily to enhance sampling of endocervical cells tracked isolates. for cytology, has been found to be the optimal instrument for If the woman is asymptomatic, the CDC no longer recom- appropriate sampling for Chlamydia culture as well. Chlamydial mends follow-up testing for a test of cure for lower tract infec- antigen detection is insensitive and nonspecifc compared with tions (uncomplicated gonorrhea). However, studies have shown NAAT and is no longer recommended. a high rate of reinfection, so rescreening patients is prudent. C. trachomatis infection is frequently asymptomatic. Chla- Women with positive cultures for gonorrhea should have a sero- mydial screening programs have been successful at decreasing logic test for syphilis in 4 to 6 weeks, even though patients with the prevalence of the disease. Te CDC recommends annual incubating syphilis are usually cured by antibiotic combinations screening of all sexually active women 25 years of age or younger of ceftriaxone and tetracycline. Similarly, patients should be and screening of older women with risk factors (e.g., those who ofered informed consent and testing for HIV infection. have a new sex partner or multiple partners). It is important to remember that N. gonorrhoeae attaches to For all women with a chlamydial or gonorrheal infection, the columnar epithelium, so a vaginal cuf swab in women with partners should be treated. Patients should be instructed to refer prior hysterectomies is not recommended (Workowski, 2015). all sex partners of the past 60 days for evaluation and treatment and to avoid sexual intercourse until therapy is completed and Chlamydia trachomatis they and their partner have resolution of symptoms. As with gonorrhea, the gold standard of techniques used to If a woman is unsure whether her partner will be treated, identify C. trachomatis infection is NAAT. C. trachomatis also delivery of antibiotic therapy (by prescription or medication)

Obstetrics & Gynecology Books Full Outline

´ Infections of the vulva ´ Infections of the vagina ´ Infections of the cervix Thank you! youtube channel: Ina Irabon www.wordpress.com: Doc Ina OB Gyne