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CHAPTER 153: Sexually Transmitted Infections 1013 Clinical Features The incubation period averages 3 weeks following initial inoculation, but varies from a few days to several weeks. After the fungus enters the body through a break in the skin, three types of local ized infections may occur. The fixed cutaneous type is characterized by lesions restricted to the site of inoculation and may appear as a crusted ulcer or verrucous plaque ( Figure 152-7). Local cutaneous-type infec tions also remain local but present as a subcutaneous nodule or pustule. The surrounding skin becomes erythematous and may ulcerate, result ing in a chancre. Local lymphadenitis is common. The lymphocutaneous type is the third and most common type. It is characterized by an initial painless nodule or papule at the site of inoculation that later develops subcutaneous nodules with clear skip areas along local lymphatic chan nels (Figure 152-8). The local reactions in all three types of infections tend to be relatively painless, but show no signs of improvement without treatment. FIGURE 152-7. Fixed sporotrichosis. The ulcer and surrounding erythema of fixed cutaneous sporotrichosis could be confused with a brown recluse spider bite. [Reproduced with permission from Knoop K, Stack L, Storrow A: Atlas of Emergency Medicine, 2nd ed. © 2002, McGraw-Hill, Inc., New York.] FIGURE 152-8. Sporotrichosis. Chronic lymphocutaneous type—an erythematous papule at the site of inoculation on the index finger with a linear arrangement of erythema tous dermal and subcutaneous nodules extending proximally in lymphatic vessels of the dor sum of the hand and arm. [Reproduced with permission from Wolff K, Johnson RA: Fitzpatrick’s Color Atlas and Synopsis of Clinical Dermatology, 6th ed. © 2009, McGraw-Hill, Inc., New York.] Patients occasionally develop extracutaneous illness from what is most probably hematogenous spread. Most cases of extracutaneous sporotrichosis involve the skeletal system. An indolent form of monoarticular arthritis is the most common symptom. Osteomyelitis, tenosynovitis, and carpal tunnel syndrome are occasionally seen as well. Multiarticular arthritis is usually only seen in patients with immunocompromise. Pulmonary involvement is rare, typically occurring in elderly alcoholic males and clinically resembling tuberculosis. Chronic lymphocytic meningitis can be a delayed complication of sporotrichosis infection and should be considered in patients with chronic meningeal symptoms. Diagnosis History and physical findings are the keys to diagnosis. 65 Fungal cultures are the best way to isolate the fungus, and tissue biopsy cultures often are diagnostic. Pus, synovial fluid, sputum, blood, or tis sue fragment is suitable for culture. Routine laboratory tests are nonspecific, but an increased WBC count, eosinophil count, and erythrocyte sedimentation rate may occur. The differential diagnosis includes tuberculosis, subcutaneous abscesses of tularemia, cat-scratch disease, leishmaniasis, staphylococcal lymphangitis, paracoccidioidomycosis, chromoblastomycosis, blastomycosis, bacterial pyoderma, primary syphilis, and infections caused by atypical mycobacteria such as Mycobacterium marinum. Treatment Itraconazole (100 to 200 milligrams daily for 2 to 4 weeks after all lesions have resolved) is the treatment of choice for localized and systemic infections.

chromoblastomycosis, blastomycosis, bacterial pyoderma, primary syphilis, and infections caused by atypical mycobacteria such as Mycobacterium marinum. Treatment Itraconazole (100 to 200 milligrams daily for 2 to 4 weeks after all lesions have resolved) is the treatment of choice for localized and systemic infections. 66 Fluconazole is less effective than itraconazole and should be reserved for those few patients not tolerating itracon azole. Ketoconazole has shown even poorer results than fluconazole. IV amphotericin B is effective, but adverse reactions limit its use to disseminated forms of the disease. In endemic regions or in epidemic outbreaks, a saturated solution of potassium iodide is an effective lowcost alternative. REFERENCES The complete reference list is available online at www.TintinalliEM.com. CHAPTER Sexually Transmitted Infections Karen D. Serrano INTRODUCTION Sexually transmitted infections (STIs) are a major public health problem. In 2016, there were 1.59 million cases of chlamydia infection, 468,514 cases of gonorrhea, and 27,814 cases of syphilis reported in the United States. 1 The World Health Organization estimates that 357 million people are infected each year by a curable STI.2 The primary medical goals are identifying and treating STIs, but important secondary goals include preserving future health (including fertility), protection of any sexual contacts, preventive education, and provision of instructions for future screening. Lack of treatment can contribute to infertility, cancer, and urogenital complications, as well as pregnancy complications and potential harm to a fetus in pregnant women with STIs. Failure of patients to follow up and adhere to a prescribed medical regimen complicates individual care and public health reduction efforts. Multiple STIs frequently occur together. Once an STI is diagnosed, further testing for human immunodeficiency virus (HIV) infection and hepatitis B is warranted. Because of frequent changes in treatment guidelines and resistance patterns, we recommend that the reader access the Centers for Disease Control and Prevention Morbidity and Mortality Weekly Report (http:// www.cdc.gov/mmwr) to check any modifications for treatment and also to obtain patient information in several languages. Tintinalli_Sec13_p0997-1100.indd 1013 8/2/19 8:11 PM

istance patterns, we recommend that the reader access the Centers for Disease Control and Prevention Morbidity and Mortality Weekly Report (http:// www.cdc.gov/mmwr) to check any modifications for treatment and also to obtain patient information in several languages. Tintinalli_Sec13_p0997-1100.indd 1013 8/2/19 8:11 PM 1014 SECTION 13: Infectious Diseases GENERAL PRINCIPLES FOR DIAGNOSIS AND SCREENING The signs and symptoms of an STI may be obvious, such as a genital lesion or vaginal discharge, or less specific, such as dysuria, lower abdominal pain, painful intercourse, or spotting between periods. Less specific signs lead to frequent STI underrecognition. Obtain a thorough sexual history in an objective, nonjudgmental manner to determine the risk of STI, HIV infection, or hepatitis. The young (13 to 24 years old), pregnant women, and homosexual men are all at higher risk of STI and subsequent morbidity. The Centers for Disease Control and Prevention has questions that providers can use when obtaining a sexual history and determining a patient’s risk for an STI (Table 153-1). Perform a pregnancy test in all females of childbearing potential, because pregnancy may affect treatment options. As appropriate, have chaperones present whenever breast, genital, or rectal examinations are performed. In women, perform a vaginal speculum examination, bimanual examination, and rectal examination. In males, retract the foreskin in uncircumcised patients to fully examine the area. Examine the areas between skinfolds, particularly in obese patients. Obtain directed site test specimens, which may include urine, vaginal, rectal, and urethral samples. GENERAL RECOMMENDATIONS FOR TREATMENT AND FOLLOW-UP Based on advice from the Centers for Disease Control and Prevention, we recommend the following3-5 (Table 153-2): 1. Patients with symptoms suggestive of cervicitis or urethritis who are high risk for STIs should be treated presumptively for gonorrhea and chlamydia in the ED. Treat the patient in the ED with single-dose antibiotic regimens to maximize compliance. 2. Obtain a pregnancy test and consult or refer promptly if the patient is pregnant. 3. If one STI is suspected or diagnosed, screen for other STIs (HIV infection, syphilis, and hepatitis) in the ED or through follow-up. 4. Report any notifiable infections such as Chlamydia trachomatis , gonorrhea, HIV infection, and syphilis. This is often based on final laboratory testing and can be automated. 5. Counsel all patients with suspected STIs about prevention and coinfection risks (notably HIV and hepatitis) in the ED and ensure follow-up options. Although no method aside from abstinence is 100% effective for STI prevention, male latex condoms and female condoms are useful in preventing STIs. 6. Advise that the partner(s) must seek treatment before any reengage ment in sex. 7. Arrange follow-up to ensure relief of symptoms, compliance, and STI cure. Although the Centers for Disease Control and Prevention recommends that healthcare providers in all settings routinely screen for HIV infection in all patients aged 13 to 64 years, the ED remains an underused venue for HIV screening. 6 Rapid HIV testing in the ED is not routine but is becoming more prevalent.7 SEXUALLY TRANSMITTED INFECTIONS PRESENTING WITH URETHRITIS, CERVICITIS, AND/OR DISCHARGE  CHLAMYDIAL INFECTIONS Clinical Features In the United States and the United Kingdom, C. trachomatis infection is the most frequently reported STI. It is one of the causes of nongonococcal urethritis and commonly coexists with gonorrhea infections. It is most prevalent in people <25 years of age and is often asymptomatic, especially in women, but also in men.

In the United States and the United Kingdom, C. trachomatis infection is the most frequently reported STI. It is one of the causes of nongonococcal urethritis and commonly coexists with gonorrhea infections. It is most prevalent in people <25 years of age and is often asymptomatic, especially in women, but also in men. Chlamydial infections in men can cause urethritis, epididymitis, proctitis, or Reiter’s syndrome (urethritis, conjunctivitis, and rash). Women generally have asymptomatic cervicitis when infected with Chlamydia, although if present, symptoms include vaginal discharge, bleeding between menses, and dysuria. The discharge may be mucopu rulent (Figure 153-1) when Neisseria gonorrhoeae coinfection is present. Consider urethral chlamydial infection in the differential diagnosis of sterile pyuria. Complications of chlamydia in women include pelvic inflammatory disease, ectopic pregnancy, and infertility. Diagnosis Chlamydia can be diagnosed in testing first-catch urine in both men and women or by collecting swab specimens from the endocervix or vagina in women and urethral swabs in men. Nucleic acid amplification testing is the preferred test for diagnosis, with a high sensitivity (90%) and specificity (99%) for Chlamydia. Nucleic acid amplification tests that are U.S. Food and Drug Administration cleared for use with vaginal swab specimens can be self-collected by the patient, with equal sensitivity and specificity to provider-collected swabs, a screening strategy that patients may find more tolerable. 8,9 Treatment The Centers for Disease Control and Prevention recommends single-dose azithromycin or twice-a-day doxycycline for 7 days. 10 Table 153-2 lists dosages and alternative treatment options. 3,11 Azithromycin is safe for pregnant women, and pregnant women should undergo a test of cure 3 to 4 weeks after treatment. Amoxicillin is a safe alternative in pregnancy if azithromycin cannot be given. Refer partners for testing and treatment if there was sexual contact in the last 60 days. Providers may elect to give the patient medica tion or a prescription to deliver to their partners. Known as expedited partner therapy, this approach is endorsed by the Centers for Disease Control and Prevention as a way of preventing the spread of this STI. TABLE 153-1 Centers for Disease Control and Prevention Recommended Questions for the Five Ps of Sexually Transmitted Infection (STI) Prevention 1. Partners “Are you currently sexually active?” “If no, have you ever been sexually active?” “In recent months, how many sex partners have you had?” “Are your sex partners men, women, or both?” 2. Prevention of pregnancy “Are you currently trying to conceive or father a child?” “Are you concerned about getting pregnant or getting your partner pregnant?” “Are you using contraception or practicing any form of birth control?” “Do you need any information on birth control?” 3. Protection from STI “Do you and your partner(s) use any protection against STI?” “If not, could you tell me the reason?” “If so, what kind of protection do you use?” “How often do you use this protection?” “If ‘sometimes,’ in what situations or with whom do you use protection?” “Do you have any other questions, or are there other forms of protection from STI that you would like to discuss today?” 4. Practices “What kind of sexual contact do you have or have you had? Genital (penis in the vagina)? Anal (penis in the anus)? Oral (mouth on penis, vagina, or anus)?” 5.

hom do you use protection?” “Do you have any other questions, or are there other forms of protection from STI that you would like to discuss today?” 4. Practices “What kind of sexual contact do you have or have you had? Genital (penis in the vagina)? Anal (penis in the anus)? Oral (mouth on penis, vagina, or anus)?” 5. Past history of STI “Have you ever been diagnosed with an STI?” “When?” “How were you treated?” “Have you had any recurring symptoms or diagnoses?” “Have you ever been tested for HIV or other STI?” “Would you like to be tested?” “Has your current partner or any former partners ever been diagnosed or treated for an STI?” “Were you tested for the same STI(s)?” “If yes, when were you tested?” “What was the diagnosis?” “How was it treated?” Abbreviation: HIV = human immunodeficiency virus. Tintinalli_Sec13_p0997-1100.indd 1014 8/2/19 8:11 PM CHAPTER 153: Sexually Transmitted Infections 1015 TABLE 153-2 Treatment of Sexually Transmitted Infections Sexually Transmitted Infection First-Line Treatment Alternative(s) Pregnancy/Lactation Bacterial vaginosis Metronidazole, 500 milligrams PO two times daily × 7 d Tinidazole, 2 grams PO daily × 2 d Metronidazole, 500 milligrams PO two times daily × 7 d or or or Metronidazole vaginal gel 0.75%, 5 grams intravaginally daily × 5 d Tinidazole, 1 gram PO daily × 5 d Metronidazole vaginal gel 0.75%, 5 grams intravaginally daily × 5 d or or Clindamycin vaginal cream 2%, 5 grams intravaginally at bedtime × 7 d Clindamycin, 300 milligrams PO twice daily × 7 d Clindamycin ovules, 100 milligrams intravaginally at bedtime × 3 d Chancroid Azithromycin, 1 gram PO single dose   Azithromycin, 1 gram PO single dose or   or Ceftriaxone, 250 milligrams IM single dose*   Ceftriaxone, 250 milligrams IM single dose* Ciprofloxacin, 500 milligrams PO, two times daily × 3 d Erythromycin base, 500 milligrams PO three times daily × 7 d

Clindamycin ovules, 100 milligrams intravaginally at bedtime × 3 d Chancroid Azithromycin, 1 gram PO single dose   Azithromycin, 1 gram PO single dose or   or Ceftriaxone, 250 milligrams IM single dose*   Ceftriaxone, 250 milligrams IM single dose* Ciprofloxacin, 500 milligrams PO, two times daily × 3 d Erythromycin base, 500 milligrams PO three times daily × 7 d Chlamydia (treat for Neisseria gonorrhoeae concurrently) Azithromycin, 1 gram PO single dose Erythromycin base, 500 milligrams PO four times daily × 7 d Azithromycin, 1 gram PO single dose PLUS test of cure in 3–4 wk or or or Doxycycline, 100 milligrams PO two times daily × 7 d Erythromycin ethylsuccinate, 800 milligrams PO four times daily × 7 d Amoxicillin, 500 milligrams PO three times daily × 7 d PLUS test of cure in 3–4 wk or or Levofloxacin, 500 milligrams PO once daily × 7 d Erythromycin base, 500 milligrams PO four times a day for 7 d PLUS test of cure in 3–4 wk or or Ofloxacin, 300 milligrams PO twice daily × 7 d Erythromycin base, 250 milligrams PO four times a day for 14 d PLUS test of cure in 3–4 wk Erythromycin ethylsuccinate, 800 mg orally four times a day for 7 d PLUS test of cure in 3–4 wk Erythromycin ethylsuccinate, 400 mg orally four times a day for 14 d PLUS test of cure in 3–4 wk Gonorrhea (treat for Chlamydia trachomatis concurrently) Ceftriaxone*, 250 milligrams IM single dose, AND azithromycin, 1 gram PO single dose Cefixime, 400 milligrams PO single dose, AND azithromycin, 1 gram PO single dose Ceftriaxone*, 250 milligrams IM single dose, AND azithromycin, 1 gram PO single dose or or or Ceftriaxone*, 250 milligrams IM single dose, AND doxycycline, 100 milligrams PO twice a day for 7 d Cefixime, 400 milligrams PO single dose, AND doxycycline, 100 milligrams PO twice a day for 7 d Spectinomycin 2 grams IM single dose Azithromycin, 2 grams PO single dose, PLUS gemifloxacin, 320 milligrams PO single dose Granuloma inguinale (donovanosis) Azithromycin, 1 gram PO weekly for at least 3 wk and until lesions completely healed Doxycycline, 100 milligrams PO two times daily for at least 3 wk and until lesions com pletely healed Erythromycin base, 500 milligrams PO four times daily for at least 3 wk and until lesions completely healed Azithromycin, 500 mg PO daily for at least 3 wk and until lesions completely healed or or (Continued) Tintinalli_Sec13_p0997-1100.indd 1015 8/2/19 8:11 PM

ly for at least 3 wk and until lesions com pletely healed Erythromycin base, 500 milligrams PO four times daily for at least 3 wk and until lesions completely healed Azithromycin, 500 mg PO daily for at least 3 wk and until lesions completely healed or or (Continued) Tintinalli_Sec13_p0997-1100.indd 1015 8/2/19 8:11 PM 1016 SECTION 13: Infectious Diseases TABLE 153-2 Treatment of Sexually Transmitted Infections Sexually Transmitted Infection First-Line Treatment Alternative(s) Pregnancy/Lactation Ciprofloxacin, 750 milligrams PO two times daily for at least 3 wk and until lesions com pletely healed Azithromycin, 1 gram PO weekly for at least 3 wk and until lesions completely healed or or Erythromycin base, 500 milligrams PO four times daily for at least 3 wk until lesions com pletely healed Gentamicin 1 milligram/kg IV every 8 h (if the above therapy is ineffective) Trimethoprim-sulfamethoxazole, 1 doublestrength (160/800 milligrams) tablet PO two times daily for at least 3 wk and until lesions completely healed Herpes simplex First episode Acyclovir, 400 milligrams PO three times daily × 7–10 d Acyclovir, 400 milligrams PO three times daily × 7–10 d or   or Acyclovir, 200 milligrams PO five times daily × 7–10 d Acyclovir, 200 milligrams PO five times daily × 7–10 d or   or Valacyclovir, 1 gram PO two times daily × 7–10 d Valacyclovir, 1 gram PO two times daily × 7–10 d Famciclovir, 250 milligrams PO three times daily × 7–10 d Suppressive therapy for recurrent genital herpes in patients without human immunodeficiency virus Acyclovir, 400 milligrams orally twice a day   Acyclovir, 400 milligrams PO three times daily or   or Valacyclovir 500-1000 milligrams orally once a day (500 milligrams may not be as effective as 1000) Famciclovir 250 milligrams orally twice a day Valacyclovir, 500 milligrams PO daily Severe Acyclovir, 5–10 milligrams/kg IV every 8 h × 2–7 d then oral medications for total treatment time of 10 d

Suppressive therapy for recurrent genital herpes in patients without human immunodeficiency virus Acyclovir, 400 milligrams orally twice a day   Acyclovir, 400 milligrams PO three times daily or   or Valacyclovir 500-1000 milligrams orally once a day (500 milligrams may not be as effective as 1000) Famciclovir 250 milligrams orally twice a day Valacyclovir, 500 milligrams PO daily Severe Acyclovir, 5–10 milligrams/kg IV every 8 h × 2–7 d then oral medications for total treatment time of 10 d Acyclovir, 5–10 milligrams/kg IV every 8 h × 2–7 d then oral medications for total treatment time of 10 d Lymphogranuloma venereum Doxycycline, 100 milligrams PO two times daily × 21 d Erythromycin base, 500 milligrams PO four times daily × 21 d Erythromycin base, 500 milligrams PO four times daily × 21 d Syphilis Primary, secondary, and early latent Benzathine penicillin G, 2.4 million units IM single dose Doxycycline, 100 milligrams PO two times daily × 14 d Tetracycline, 500 milligrams PO four times daily × 14 d Ceftriaxone, 1–2 grams IM or IV daily × 10–14 d Azithromycin, 1 gram PO single dose. Use only if treatment with penicillin or doxycycline is not feasible. Benzathine penicillin G, 2.4 million units IM single dose Latent Benzathine penicillin G, 2.4 million units IM one time a week × 3 wk Doxycycline, 100 milligrams PO two times daily × 28 d Tetracycline, 500 milligrams PO four times daily × 28 d Benzathine penicillin G, 2.4 million units IM one time a week × 3 wk Trichomoniasis Metronidazole, 2 grams PO single dose Metronidazole, 500 milligrams PO two times daily × 7 d Metronidazole, 2 grams PO single dose (weigh risks and benefits of treatment)or Tinidazole, 2 grams PO single dose *Ceftriaxone is painful IM and may be mixed with lidocaine 1% to decrease patient discomfort with administration. (Continued) Tintinalli_Sec13_p0997-1100.indd 1016 8/2/19 8:11 PM

s PO two times daily × 7 d Metronidazole, 2 grams PO single dose (weigh risks and benefits of treatment)or Tinidazole, 2 grams PO single dose *Ceftriaxone is painful IM and may be mixed with lidocaine 1% to decrease patient discomfort with administration. (Continued) Tintinalli_Sec13_p0997-1100.indd 1016 8/2/19 8:11 PM CHAPTER 153: Sexually Transmitted Infections 1017 Universal adoption of this method at this time is incomplete because of ethical issues and medicolegal consequences including some state prohibitions. 12 Providers should visit www.cdc.gov/std/ept to obtain updated information for their state. Counsel patients to avoid sexual contact until 7 days have elapsed after completion of antibiotic treatment and their symptoms have resolved. Encourage women to be retested approximately 3 months after treatment because of the high incidence of recurrence.  GONOCOCCAL INFECTIONS Gonorrhea is the second most commonly reported STI, caused by N. gonorrhoeae, a gram-negative diplococcus. Clinical Features Most gonococcal infections in women are asymptomatic and often coexist with chlamydial infection. Gonorrheal infections result in complications ranging from ectopic pregnancy to chronic pelvic pain to pelvic inflammatory disease. Symptoms, if present, may include nonspecific lower abdominal discomfort and mucopurulent cervicitis after a 7- to 14-day incubation period. In contrast to women, gonorrheal infection is usually symptomatic in men, and 80% to 90% of men develop symptoms within 2 weeks of exposure. Dysuria and profuse, purulent penile discharge (Figure 153-2) are the most common presenting symptoms, but symptoms of acute epididymitis and prosta titis may also result. Rectal infection with mucopurulent anal discharge and pain occurs in 30% to 50% of women with gonococcal cervicitis, and the rectum can be the only site of infection in homosexual men. N. gonorrhoeae also can be isolated from the pharynx but rarely causes pharyngitis. FIGURE 153-1. Viscous, opaque discharge emanating from the cervical os, consistent with mucopurulent cervicitis. The string from an intrauterine device is seen descending through the os in this patient. [Reproduced with permission from Knoop KJ, Stack LB, Storrow AB, Thurman RJ: The Atlas of Emergency Medicine, 3rd ed. © 2009 by McGraw-Hill, Inc., New York.] FIGURE 153-2. Gonococcal urethritis in a male. Mucopurulent ureteral discharge is caused by infection with Neisseria gonorrhoeae. [Reproduced with permission from Goldsmith LA, Katz SI, Gilchrest BA, et al: Fitzpatrick’s Dermatology in General Medicine, 8th ed. © 2012 by McGraw-Hill, Inc., New York.] FIGURE 153-3. Disseminated gonococcal infection. A. Maculopapules on the hands. B. Lesion on the extensor surface of the wrist in a sexually active adult female. The macropapule has a petechial component and an erythematous periphery. Signs and symptoms of disseminated gonococcal infection include petechial or pustular acral skin lesions on an erythematous base (Figure 153-3), asymmetric arthralgias, tenosynovitis or septic arthritis, and fever or general malaise. Infection with N. gonorrhoeae and other STIs is associated with increased HIV shedding. Diagnosis The Centers for Disease Control and Prevention recom mends that nucleic acid amplification testing be performed on cervical, vaginal, urethral, or urine specimens. Specimens can be self-collected by the patient. Not all nucleic acid amplification testing is the same; some tests can be used only on certain specimen types, so know what is available at your institution. Culture and nucleic acid hybridization tests require endocervical or urethral swab specimens.

or urine specimens. Specimens can be self-collected by the patient. Not all nucleic acid amplification testing is the same; some tests can be used only on certain specimen types, so know what is available at your institution. Culture and nucleic acid hybridization tests require endocervical or urethral swab specimens. In men, a Gram stain of urethral secretions that demonstrates poly morphonuclear leukocytes with the classic intracellular diplococci confirms the diagnosis. However, absence of this finding is not sufficient to rule out the gonococcal infection, and it is therefore not recommended as a screening tool. Additionally, this diagnostic method is not sufficient for endocervical, pharyngeal, or rectal specimens. Diagnosis of disseminated gonococcal infection is difficult, with only 20% to 50% of cultures of blood, lesion, and joint specimens yielding positive results. Culture of cervical, rectal, and pharyngeal specimens may improve the chance of diagnosis. Treatment Given emerging resistance patterns, the Centers for Disease Control and Prevention recommends dual therapy with ceftriaxone 250  milligrams IM plus single-dose azithromycin 1 gram PO for the treatment of gonorrhea (Table 153-2). 3,5 Fluoroquinolones are no longer recommended for first-line treatment of gonorrhea because of antibiotic resistance. Pregnant women should be treated with a cephalosporin plus azithromycin or, if allergic to cephalosporins, with 2 grams of either azithromycin PO or 2 grams of spectinomycin IM (not available in the United States) in a single dose. Instructions to sexual contacts are the same as with chlamydial infections. Treat disseminated disease Tintinalli_Sec13_p0997-1100.indd 1017 8/2/19 8:12 PM

ycin or, if allergic to cephalosporins, with 2 grams of either azithromycin PO or 2 grams of spectinomycin IM (not available in the United States) in a single dose. Instructions to sexual contacts are the same as with chlamydial infections. Treat disseminated disease Tintinalli_Sec13_p0997-1100.indd 1017 8/2/19 8:12 PM 1018 SECTION 13: Infectious Diseases with higher doses of ceftriaxone (1 gram IM or IV every 24 hours for 1 to 2 days) followed by cefixime 400 milligrams PO twice a day for a minimum of 1 week. Gonococcemia requires hospitalization for IV administration of antibiotics and evaluation for possible endocarditis and meningitis. Patients with gonococcal arthritis rarely require surgical drainage and irrigation of affected joints.  NONGONOCOCCAL URETHRITIS Nongonococcal urethritis is diagnosed when N. gonorrhoeae is absent in someone with clinical symptoms. Although nongonococcal urethri tis is usually caused by C. trachomatis, other causes of nongonococcal urethritis include Ureaplasma urealyticum , Mycoplasma genitalium , Trichomonas vaginalis, herpes simplex virus, and adenovirus. Alter native pathogens are seen more often in older men, and often no singular pathogen is identified. Specific tests for U. urealyticum and M. genitalium are not indicated. If a patient’s urethral specimen has five or more WBCs per oil immersion field or the first-void urine specimen suggests infection, treat empirically as chlamydial urethritis. If the symptoms persist, the patient was noncompliant with their prior treatment regimen, the patient was exposed to a new sexual partner, or the previous partner was not treated, repeat treatment for chlamydial urethritis. Otherwise, obtain a specimen for culture for T. vaginalis and treat with metronidazole, 2 grams as a single oral dose, or with a combination of tinidazole, 2 grams PO, plus azithromycin, 1 gram PO as a single dose.  TRICHOMONAL INFECTIONS T. vaginalis is a flagellated protozoan that causes urogenital infections mostly in women, with a prevalence of approximately 3%. T. vaginalis infection is associated with a high prevalence of coinfection with other STIs, notably HIV , and trichomonas has been identified as a cofactor in HIV transmission. 14,15 Trichomonas is also covered in Chapter 102 “Vulvovaginitis. ” Clinical Features Trichomoniasis can range from asymptomatic car rier states to severe, inflammatory disease. Symptoms include a mal odorous, thin watery discharge, vulvar irritation, pruritus, dysuria, urinary frequency, dyspareunia, and occasionally low abdominal pain. The classic yellow-green, frothy discharge is infrequently found, and many women have minimal symptoms. 3 Physical examination may demonstrate vulvar irritation, inflamed vaginal mucosa, and punctate cervical hemorrhages. In men, the disease is often asymptomatic, but may present as urethritis. Diagnosis Nucleic acid amplification tests and other highly sensitive tests are recommended for diagnosis of trichomoniasis, preferred over wet-mount microscopy, a method with poor sensitivity. Culture is the most sensitive and specific test available, although it may take up to 7 days to obtain results. Because of this delay to diagnosis, commercially available tests using DNA probes and monoclonal antibodies are used in some institutions. Treatment All patients with Trichomonas infection should be treated irrespective of symptoms, and sexual partners should be treated to prevent reinfection. Metronidazole, 2 grams PO in a single dose or 500 milligrams PO twice daily for 7 days, cures 90% to 95% of patients. Single-dose regimens are generally preferred due to better adherence, decreased cost, and less vaginal candidiasis, whereas the lower dose, prolonged course has fewer systemic side effects.

reinfection. Metronidazole, 2 grams PO in a single dose or 500 milligrams PO twice daily for 7 days, cures 90% to 95% of patients. Single-dose regimens are generally preferred due to better adherence, decreased cost, and less vaginal candidiasis, whereas the lower dose, prolonged course has fewer systemic side effects. 3 Patients must avoid alcohol when taking metronidazole given the disulfiram-like reaction. Metronidazole gel is less effective than oral treatment. Trichomonas infections are linked to an increase in pregnancy-related complications. Because metronidazole is a pregnancy category B drug, it is the drug of choice for treating symptomatic pregnant patients, with no high-quality evidence linking metronidazole exposure with terato genic effects. 16 Despite the Centers for Disease Control and Prevention recommendations of a 2-gram singular dose coupled with evidence supporting the safety of metronidazole treatment in symptomatic preg nant women, some clinicians avoid oral treatment in the first trimester. Treatment of partners includes administration of the same medications as for the patient plus an STI clinic referral given the high rate of cotransmission of other STIs. SEXUALLY TRANSMITTED INFECTIONS PRESENTING WITH GENITAL ULCERS Genital ulcers are caused by syphilis, herpes virus infection, chancroid, lymphogranuloma venereum, and granuloma inguinale (donovanosis). These infections have high rates of coinfection with HIV . Not all infections associated with genital ulcers are sexually transmitted. Characteristics of the lesions and their accompanying signs and symptoms are provided in Table 153-3.  SYPHILIS Syphilis is a systemic disease caused by the spirochete Treponema pallidum. The organism enters the body through mucous membranes or nonintact skin. T. pallidum remains very sensitive to penicillin. The incidence of syphilis in the United States has been on the rise from 2000 to 2016. This was initially attributed to increased cases of male-to-male transmission; however, between 2013 and 2016, there was a significant increase in cases among women. The spike in cases in women is of particular concern because rising syphilis rates in women correlate with a rise in congenital syphilis. Clinical Features Syphilis is divided into three stages of infection— primary, secondary, and tertiary—and the disease may be diagnosed in any of these stages. Latent syphilis is characterized by absence of clinical manifestations but positive serologic testing. TABLE 153-3 Clinical Features of Genital Ulcerative Infections Disease Clinical Diagnosis Presence of Pain Inguinal Adenopathy Comment Syphilis Indurated, relatively clean base; heals spontaneously No Firm, rubbery, discrete nodes; not tender Primary: chancre Secondary: rash, mucocutaneous lesions, lymphadenopathy Tertiary: cardiac, ophthalmic, auditory, CNS lesions Herpes simplex virus infection Multiple small, grouped vesicles coalescing and forming shallow ulcers; vulvovaginitis Yes Tender bilateral adenopathy Cytologic detection insensitive; false-negative culture results common; type-specific serologic test Chancroid (Haemophilus ducreyi) Multiple painful, irregular, purulent ulcers with potential exudative base Yes 50% painful, suppurative, inguinal lymph nodes potentially requiring drainage Cofactor for human immunodeficiency virus transmission; 10% have coinfections with herpes simplex virus infection or syphilis Lymphogranuloma venereum Small and shallow ulcer, associated proctocolitis with fistulas and strictures No Tender lymph nodes Caused by Chlamydia trachomatis L1, L2, L3 Granuloma inguinale (donovanosis) Painless, beefy red, bleeding ulcers No No Endemic in Africa, Australia, India, New Guinea; rare in United States Tintinalli_Sec13_p0997-1100.indd 1018 8/2/19 8:12 PM

associated proctocolitis with fistulas and strictures No Tender lymph nodes Caused by Chlamydia trachomatis L1, L2, L3 Granuloma inguinale (donovanosis) Painless, beefy red, bleeding ulcers No No Endemic in Africa, Australia, India, New Guinea; rare in United States Tintinalli_Sec13_p0997-1100.indd 1018 8/2/19 8:12 PM CHAPTER 153: Sexually Transmitted Infections 1019 Primary syphilis, or the initial stage of infection, is characterized by a painless chancre with indurated borders on the penis (Figure 153-4), vulva (Figure 153-5), or other areas of sexual contact. The incubation period is approximately 21 days, with lesions disappearing after 3 to 6 weeks. There are no constitutional symptoms, and a lesion may even be absent with primary disease. The lesion resolves spontaneously. Secondary syphilis develops 3 to 6 weeks after the end of the primary stage and is characterized by rash and lymphadenopathy. Nonspecific symptoms of sore throat, malaise, fever, and headaches are common. The rash often starts on the trunk ( Figure 153-6) and flexor surfaces of the extremities, spreading to the palms ( Figure 153-7) and soles. The rash takes on many forms but is often dull red-pink and papular. Secondary syphilis resolves spontaneously. Tertiary or latent syphilis develops in about one third of patients after secondary syphilis, occurring 3 to 20 years after the initial infec tion. Involvement of the nervous and cardiovascular systems is char acteristic, with widespread granulomatous lesions (gummata). Specific manifestations include meningitis, dementia, neuropathy (tabes dorsalis), and thoracic aneurysm. Diagnosis T. pallidum cannot be cultured in the laboratory, and there is no single optimal test. The sensitivity and specificity of tests for syphilis depend on the stage of the disease and the type of test. Direct visualization of the organism using darkfield microscopy is diagnostic FIGURE 153-4. Painless chancre. [Reproduced with permission from Wolff KL, Johnson  R, Suurmond R: Fitzpatrick’s Color Atlas & Synopsis of Clinical Dermatology, 5th ed. © 2005, McGraw-Hill, Inc., New York.] FIGURE 153-5. Syphilis chancre in a female. A painless ulcer is seen on the vulva. [Reproduced with permission from Goldsmith LA, Katz SI, Gilchrest BA, et al: Fitzpatrick’s Dermatology in General Medicine, 8th ed. © 2012 by McGraw-Hill, Inc., New York.] FIGURE 153-6. Disseminated papulosquamous eruption on the right chest wall characteristic for secondary syphilis. [Reproduced with permission from Wolff K, Johnson RA, Saavedra AO: Fitzpatrick’s Color Atlas and Synopsis of Clinical Dermatology, 7th ed. © 2013 by McGraw-Hill, Inc., New York.] of primary, secondary, or early congenital syphilis, no matter what the results on serology. However, failure to visualize the organism does not exclude syphilis. Nontreponemal tests (Venereal Disease Research Laboratory test, rapid plasma reagin test) detect nonspecific antibodies to cardiolipins, which are released as a result of infection. The Venereal Disease Research Laboratory and rapid plasma reagin tests are used as screening tests and also, once diagnosis is made, to assess disease activity and response to treatment. If used for screening, the Venereal Disease Research Laboratory and rapid plasma reagin tests are associated with both false-negative and false-positive results. Tests do not become positive until about 1 to 4 weeks after a chancre appears. Positive results must be confirmed with an immunoassay specific for T. pallidum antibodies. Some laboratories now begin the testing sequence with sensitive and specific Treponema-specific assays (reverse screening) and follow response to treatment with nontreponemal tests.

il about 1 to 4 weeks after a chancre appears. Positive results must be confirmed with an immunoassay specific for T. pallidum antibodies. Some laboratories now begin the testing sequence with sensitive and specific Treponema-specific assays (reverse screening) and follow response to treatment with nontreponemal tests. For secondary syphilis, nontreponemal antibody tests are nearly 100% sensitive with high specificity.18 The blood of treated patients usually becomes nonreactive on nontreponemal antibody tests. Patients who develop disease and have a reactive result on a specific trepone mal antibody test will have a reactive test result for life regardless of disease activity or treatment. A presumptive diagnosis of syphilis is made if a positive result on a nontreponemal antibody test (i.e., rapid plasma reagin or Venereal Disease Research Laboratory test) is supported by a positive confirma tory result on a treponemal antibody test (i.e., fluorescent treponemal antibody absorption test). 18,19 Treat based on strong clinical grounds while results of confirmatory tests are pending, if follow-up is uncer tain. When uncertain about testing interpretation, review the Centers for Disease Control and Prevention website (http://www.cdc.gov/STD/ syphilis/default.htm) for detailed clarification of laboratory diagnosis or contact the local health department. Treatment For primary and secondary syphilis, treat with penicillin G benzathine, 2.4 million units IM in a single dose. Doxycycline twice daily for 2 weeks may be used in penicillin-allergic patients ( Table 153-2). Pregnant women should be treated with parenteral penicillin G; if allergic, they should be desensitized and then given this medication. The Jarisch-Herxheimer reaction occurs most frequently in treatment of early syphilis and is characterized by an acute febrile reaction associated with headache and myalgias within the first 24 hours after treatment. Inform patients about this possible reaction. Recommend treatment of sexual partner(s) exposed in the previous 90 days. For a more detailed explanation of partner treatment, please refer to the Centers for Disease Control and Prevention website (http://www.cdc.gov/std/ept/ default.htm). Treat tertiary syphilis with 2.4 million units of penicillin G benzathine IM weekly for 3 weeks. Either a primary care physician or the department of public health should closely follow all patients for repeat serologic testing at 6 and 12 months. Tintinalli_Sec13_p0997-1100.indd 1019 8/2/19 8:12 PM

/ept/ default.htm). Treat tertiary syphilis with 2.4 million units of penicillin G benzathine IM weekly for 3 weeks. Either a primary care physician or the department of public health should closely follow all patients for repeat serologic testing at 6 and 12 months. Tintinalli_Sec13_p0997-1100.indd 1019 8/2/19 8:12 PM 1020 SECTION 13: Infectious Diseases FIGURE 153-8. Genital herpes in a male. These formerly vesicular lesions have crusted over. [Reproduced with permission from Goldsmith LA, Katz SI, Gilchrest BA, et al: Fitzpatrick’s Dermatology in General Medicine, 8th ed. © 2012 by McGraw-Hill, Inc., New York.] FIGURE 153-9. Genital herpes in a female. These formerly vesicular lesions have crusted over. [Reproduced with permission from Goldsmith LA, Katz SI, Gilchrest BA, et al: Fitzpatrick’s Dermatology in General Medicine, 8th ed. © 2012 by McGraw-Hill, Inc., New York.]  HERPES SIMPLEX INFECTIONS Herpes simplex virus (HSV) type 1 or type 2 infections are lifelong. Genital herpes results from exposure of mucosal surfaces or nonintact skin to the HSV virus. While most genital infections are caused by the HSV-2 virus, the incidence of anogenital infections caused by HSV-1 virus is on the rise, especially among young women and men who have sex with men. 20 Only 10% to 25% of individuals who are HSV-2 seropositive report a history of genital herpes, which suggests that most infected people have unrecognized or asymptomatic infections. Viral shedding in persons who are unaware that they are infected is likely responsible for the majority of HSV transmission. 3 HSV is also covered in Chapter 102. Clinical Features “Classic” outbreaks of primary genital HSV infec tion begin with a prodrome lasting 2 to 24 hours that is characterized by localized or regional pain, tingling, and burning. Next, constitu tional symptoms of headache, fever, painful inguinal lymphadenopathy, anorexia, and malaise develop. As the disease progresses, papules and vesicles on an erythematous base become evident, which eventually ulcerate. Patterns of HSV-1 and HSV-2 infection appear identical: vesicles usually are uniform in size, and the tense center umbilicates to form a depressed center. Lesions usually crust and then reepithelialize and heal without scarring. In men, HSV ulcers often appear on the shaft or glans of the penis (Figure 153-8). In women, ulcers can occur on the introitus (Figure 153-9), urethral meatus, labia, and perineum. Lesions are exquisitely painful and may be associated with serous discharge. In both sexes, lesions may be found on the perianal area, thighs, or buttocks. Dysuria is common in women, and urinary retention may develop secondary to severe pain. Complete healing usually occurs within 3 weeks, and viral shedding persists for 10 to 12 days after the onset of the rash. Recurrent outbreaks are typically milder than the initial episode. There are typically fewer lesions, and viral shedding occurs at a lower concentration and for a shorter duration (i.e., about 3 days). Diagnosis Diagnosis is usually made based on clinical features. Labo ratory diagnosis is either by cell culture or polymerase chain reaction. When obtaining a specimen for analysis, puncture the vesicle and swab the fluid. Swab the base of the lesion vigorously, because the virus is cell associated. 3 Importantly, lack of HSV detection does not confirm absence of HSV infection because viral shedding is intermittent. Treatment Treatment shortens the duration of outbreaks but is not curative. Antiviral medications decrease the time until all lesions are crusted and healed, decrease pain and constitutional symptoms, and decrease the period of viral shedding by several days. Treat the first clinical episode of genital herpes with acyclovir, famciclovir, or valacyclovir ( Table 153-2).

aks but is not curative. Antiviral medications decrease the time until all lesions are crusted and healed, decrease pain and constitutional symptoms, and decrease the period of viral shedding by several days. Treat the first clinical episode of genital herpes with acyclovir, famciclovir, or valacyclovir ( Table 153-2). To treat proctitis or oral infec tions, use higher dosages (acyclovir, 400 milligrams five times a day for 7 to 10 days). For hospitalized patients with severe disease, administer acyclovir, 5 to 10 milligrams/kg IV every 8 hours, for at least 2 days before transitioning to oral therapy. Treat episodic recurrent infection for 5 days with acyclovir, fam ciclovir, or valacyclovir at dosages reduced from primary therapy (Table 153-2). For individuals with frequent recurrences, suppressive therapy is a good option and reduces the frequency of recurrences by FIGURE 153-7. Papulosquamous eruption on the right palm characteristic for secondary syphilis. [Reproduced with permission from Goldsmith LA, Katz SI, Gilchrest BA, et al: Fitzpatrick’s Dermatology in General Medicine, 8th ed. © 2012 by McGraw-Hill, Inc., New York.] Tintinalli_Sec13_p0997-1100.indd 1020 8/2/19 8:12 PM

FIGURE 153-7. Papulosquamous eruption on the right palm characteristic for secondary syphilis. [Reproduced with permission from Goldsmith LA, Katz SI, Gilchrest BA, et al: Fitzpatrick’s Dermatology in General Medicine, 8th ed. © 2012 by McGraw-Hill, Inc., New York.] Tintinalli_Sec13_p0997-1100.indd 1020 8/2/19 8:12 PM CHAPTER 153: Sexually Transmitted Infections 1021 FIGURE 153-10. Painful, punched-out ulcer of chancroid. [Reproduced with permis sion from Fleischer AB Jr, Feldman SR, McConnell CF, et al: Emergency Dermatology: A Rapid Treatment Guide. © 2002, McGraw-Hill, Inc., New York.] FIGURE 153-11. Chancroid with characteristic penile ulcers and associated left ingui nal adenitis. [Photo contributor: H. Hunter Handsfield. Atlas of Sexually Transmitted Diseases . New York: McGraw-Hill, Inc.; 1992. Reproduced with permission from Knoop K, Stack L, Storrow A, Thurman RJ: Atlas of Emergency Medicine , 3rd ed. © 2010, McGraw-Hill, Inc., New York. Fig 9-22.] 70% to 80% (according to the Centers for Disease Control and Prevention). Treat severe recurrent infections (seen primarily in immunocompromised patients) with acyclovir, 5 to 10 milligrams/kg every 8 hours IV , for at least 2 days before switching to oral therapy. A primary diagnosis of HSV should prompt the search for other STIs including HIV .  CHANCROID Chancroid is a disease characterized by painful genital ulcers and lymphadenitis that is caused by the pleomorphic gram-negative bacillus Haemophilus ducreyi. The disease is on the decline in the United States, and infections are usually seen in association with sporadic outbreaks. Chancroid increases HIV transmission and often is accompanied by other infections. When chancroid is present, 10% of infected patients in the United States also have HSV or T. pallidum. Clinical Features A painful erythematous papule appears at the site of infection (usually confined to the genital region) after an incubation period of 4 to 10 days. One to 2 days later, the lesion becomes eroded, ulcerated, and often pustular. The ulcers are usually 1 to 2 cm in diameter with sharp, undermined margins and are very painful ( Figure 153-10). The friable base of the ulcer is covered with yellow-gray necrotic exu dates. Multiple lesions are present in up to 50% of patients, especially in women, and “kissing lesions” (infection of adjacent skin areas due to autoinoculation) are frequent. Painful inguinal lymphadenopathy develops 1 to 2 weeks after primary infection, and lymph nodes may become necrotic or pus-filled, known as buboes. (Figure 153-11). Constitutional symptoms are rare, and ulcerations are rarely recurrent. Diagnosis Diagnosis can generally be made on clinical grounds with a painful ulcer and regional lymphadenopathy, but other infections (such as HSV infection and syphilis) are possible. A swab of a lesion or pus from a suppurative lymph node can be cultured, but a special medium is required that is not widely available, and culturing has a sensitivity of <80%. There is no current U.S. Food and Drug Administration– approved polymerase chain reaction test, but some clinical laboratories have developed their own polymerase chain reaction tests. Treatment Azithromycin PO in a single dose, ceftriaxone IM in a single dose, ciprofloxacin for 3 days, or erythromycin base for 7 days are all effective in the treatment of H. ducreyi infection (Table 153-2). Treatment choice should be based on local antibiotic resistance patterns and patient factors. Generally, azithromycin and ceftriaxone are used in patients without HIV infection, with ciprofloxacin as an alternative. Erythromycin is inexpensive, but the need for multiple doses and GI toxicity make it less desirable.

2). Treatment choice should be based on local antibiotic resistance patterns and patient factors. Generally, azithromycin and ceftriaxone are used in patients without HIV infection, with ciprofloxacin as an alternative. Erythromycin is inexpensive, but the need for multiple doses and GI toxicity make it less desirable. Incision and drainage or aspiration of buboes can be considered for symptomatic relief, prevention of fistulas, and secondary ulcers. Symptoms improve in about 3 days, and lesions are visibly improved within a week. Larger ulcers may require 2 to 3 weeks to heal. Partners should be treated if they have had sexual contact in the past 10 days, regardless of symptoms. 3 Pregnant women should be treated with azithromycin or ceftriaxone. All patients should be tested for HSV , syphilis, and HIV at the time of diagnosis of chancroid and again 3 months later if tests are initially negative.  LYMPHOGRANULOMA VENEREUM Lymphogranuloma venereum is a sexually transmitted infection caused by three specific serotypes of C. trachomatis (L1, L2, and L3). It is also known as struma, tropical bubo, or Durand-Nicolas-Favre disease. Lymphogranuloma venereum is endemic worldwide, but is seen only sporadically in the United States. The Netherlands has seen an increased incidence of this STI in men who have sex with men. 23 The primary lesion can take many forms and be confused with the lesions of other STIs (Table 153-3). Clinical Features The painless primary chancre usually goes unnoticed and lasts only 2 to 3 days ( Figure 153-12). Generally, 1 to 3 weeks after the appearance of the initial lesion, unilateral inguinal lymphade nopathy is noted (60% of cases) ( Figure 153-13). Often the overlying skin has a purplish hue. The initial lesion progresses to suppurative FIGURE 153-12. Lymphogranuloma venereum chancre. This ulceration was painless to the patient. [Reproduced with permission from Goldsmith LA, Katz SI, Gilchrest BA, et al: Fitzpatrick’s Dermatology in General Medicine, 8th ed. © 2012 by McGraw-Hill, Inc., New York.] Tintinalli_Sec13_p0997-1100.indd 1021 8/2/19 8:12 PM

e FIGURE 153-12. Lymphogranuloma venereum chancre. This ulceration was painless to the patient. [Reproduced with permission from Goldsmith LA, Katz SI, Gilchrest BA, et al: Fitzpatrick’s Dermatology in General Medicine, 8th ed. © 2012 by McGraw-Hill, Inc., New York.] Tintinalli_Sec13_p0997-1100.indd 1021 8/2/19 8:12 PM 1022 SECTION 13: Infectious Diseases FIGURE 153-14. An example of the linear depression parallel to the inguinal ligament in lymphogranuloma venereum, the groove sign. [Reproduced with permission from Goldsmith LA, Katz SI, Gilchrest BA, et al: Fitzpatrick’s Dermatology in General Medicine, 8th ed. © 2012 by McGraw-Hill, Inc., New York.] FIGURE 153-15. Granuloma inguinale in a male. The painless, ulcerative lesion is classically beefy red and bleeds easily. [Reproduced with permission from Goldsmith LA, Katz SI, Gilchrest BA, et al: Fitzpatrick’s Dermatology in General Medicine, 8th ed. © 2012 by McGraw-Hill, Inc., New York.] FIGURE 153-13. Lymphogranuloma venereum. Marked lymphadenopathy with small central eschar/ulcer. [Reproduced with permission from Wolff KL, Johnson R, Suurmond R: Fitzpatrick’s Color Atlas & Synopsis of Clinical Dermatology, 5th ed. © 2005, McGraw-Hill, Inc., New York.] be treated. The Centers for Disease Control and Prevention may be able to assist with testing. Treatment Doxycycline for 21 days is the preferred regimen, with erythromycin base as an alternative (Table 153-2). Mild untreated cases resolve spontaneously in 8 to 12 weeks. Treat pregnant or lactating women with erythromycin or azithromycin. Refer partners with whom the individual has had sexual contact within the past 60 days for treat ment. Sexual activity should be avoided until the full course of antibiotic treatment is completed and lymphadenopathy has resolved.  GRANULOMA INGUINALE (DONOVANOSIS) Granuloma inguinale, also called donovanosis, is caused by Klebsiella granulomatis, a gram-negative intracellular bacterium. The disease is rare in the United States but is endemic in India, the Caribbean, south ern Africa, and central Australia. Clinical Features After a variable incubation period of 2 weeks to 6 months, granuloma inguinale begins as subcutaneous nodules on the penis or vulva. The nodules then progress to the more classic painless, ulcerative lesions ( Figure 153-15). These lesions are highly vascular, which explains both their beefy red appearance and their tendency to bleed easily on contact. Lymphadenopathy is not usually present, but subcutaneous granulomas may occur and mimic lymphadenopathy. Superinfection may complicate these open, bleeding lesions and obscure the diagnosis. Granuloma inguinale is not highly contagious, and mul tiple exposures are required to contract the disease. Autoinoculation can occur, leading to oral and GI tract involvement. Diagnosis K. granulomatis is difficult to culture, and diagnosis often requires visualization of characteristic Donovan bodies on tissue biopsy. Treatment Treatment of choice is azithromycin 1 gram PO weekly or 500 mg PO daily for at least 3 weeks and until all lesions have healed (Table 153-2). Doxycycline, ciprofloxacin, erythromycin base, and trimethoprimsulfamethoxazole are alternatives for at least 3 weeks and until the lesions heal. Doxycycline, ciprofloxacin, and sulfonamides are contraindicated in pregnancy. Erythromycin base is the recommended treatment for pregnant or lactating women with the potential addition of a parenteral aminoglycoside. Individuals with whom the patient had sexual contact within 60 days of the appearance of the lesions should also be treated if symptomatic.  HUMAN PAPILLOMAVIRUS INFECTION Over 40 different genotypes of human papillomavirus (HPV) can infect the human genital tract. It is estimated that just under 25% of the U.S.

side. Individuals with whom the patient had sexual contact within 60 days of the appearance of the lesions should also be treated if symptomatic.  HUMAN PAPILLOMAVIRUS INFECTION Over 40 different genotypes of human papillomavirus (HPV) can infect the human genital tract. It is estimated that just under 25% of the U.S. population is currently infected with genital HPV . 25 As many as half of these infections are in adolescents and young adults, age 15 to 24 years.25 lymphadenopathy, resulting in either spontaneous abscess rupture or firm inguinal masses. Lymphogranuloma venereum proctitis (rectal ulcers, bleeding, and discharge) is also seen, primarily in homosexual men, and can be mistaken for inflammatory bowel disease. Scarring of these masses may cause linear depressions parallel to the inguinal liga ment, forming the so-called groove sign (Figure 153-14). Lymphogranuloma venereum infections can cause fever, chills, arthralgias, erythema nodosum, or rarely meningoencephalitis. Lymphogranuloma venereum is easily confused with syphilis, chancroid, and HSV , and it also facili tates the transmission and acquisition of HIV . Diagnosis Diagnosis is based on clinical suspicion, epidemiologic data, and exclusion of other causes. Chlamydia serologic testing for lymphogranuloma venereum is not standardized and not helpful except to support the diagnosis in the appropriate setting. Culture, direct immunofluorescence testing, and nucleic acid detection of a lesion swab or bubo aspirate are not widely available, nor is genotyping. Given these diagnostic constraints, patients with a clinical picture suggestive of lymphogranuloma venereum and epidemiologic information should simply Tintinalli_Sec13_p0997-1100.indd 1022 8/2/19 8:12 PM

testing, and nucleic acid detection of a lesion swab or bubo aspirate are not widely available, nor is genotyping. Given these diagnostic constraints, patients with a clinical picture suggestive of lymphogranuloma venereum and epidemiologic information should simply Tintinalli_Sec13_p0997-1100.indd 1022 8/2/19 8:12 PM CHAPTER 153: Sexually Transmitted Infections 1023 FIGURE 153-16. Condylomata acuminata in a 25-year-old male with a 3-month his tory of penile lesions. Multiple cauliflower floret–like papules are seen on the penile shaft and foreskin. [Reproduced with permission from Wolff K, Johnson RA: Fitzpatrick’s Color Atlas and Synopsis of Clinical Dermatology, 6th ed. © 2009 by McGraw-Hill, Inc., New York.] FIGURE 13-17. Condylomata acuminata of the vulva. Multiple pink-brown, soft papules are seen on the labia. [Reproduced with permission from Wolff K, Johnson RA, Saavedra AO: Fitzpatrick’s Color Atlas and Synopsis of Clinical Dermatology , 7th ed. © 2013 by McGraw-Hill, Inc., New York.] HPV infection is so common that most sexually active adults become infected at some point in their lives, and the majority of infections are asymptomatic. HPV infection is clinically important because oncogenic, high-risk subtypes of HPV (e.g., HPV types 16 and 18) cause most cases of cervical, vulvar, penile, anal, and oropharyngeal cancers. 26 Nononcogenic subtypes, such as HPV types 6 and 11, cause genital warts. Several vaccines with activity against HPV have been developed, with a primary goal of preventing cancer. The bivalent vaccine (Cervarix ® ) works against oncogenic genotypes 16 and 18 only. The quadrivalent vaccine (Gardasil ® ) works against genotypes 16 and 18 as well as genotypes 6 and 11 associated with genital warts. A 9-valent vaccine (Gardasil-9 ® ) protects against infection with genotypes 16, 18, 6, and 11, as well as five additional types associated with cervical cancer. 3 A two-dose vaccine series is recommended for girls and boys who initiate the vaccination series between ages 9 and 14. Three vaccine doses are recommended for those who began the series between ages 15 and 26 and immunocompromised individuals. Clinical Features The majority of cases of HPV infection are asymp tomatic, and most people clear serologic evidence of HPV spontane ously. Infection with subtypes leading to genital warts may prompt patients to seek care. Genital warts are flesh-colored papules or cauliflower-like projections that usually appear after an incubation period of 1 to 8 months and may coalesce to form condylomata acuminata (Figure 153-16). In women, they are seen on the external genitalia (Figure 153-17) and in the perianal region. Genital warts are usually painless, but depending on their anatomic location, they can be friable, painful, or pruritic and often enlarge during pregnancy. Infected males often complain of nonhealing penile lesions, occasionally with pruritus and urethral discharge. Perianal condylomata have been seen in up to 80% of women with vulvar condylomata and are seen frequently in homosexual males. Diagnosis Diagnosis is clinical. Treatment Many topical treatments for genital warts exist that can be used for days to weeks, but these are not usually initiated in the ED. Treatment decisions are based on the size and number of lesions, the amount of discomfort they are causing, and patient preferences. The treatment of external genital warts may help reduce viral load but is not a cure. All treatment options are considered equally effective and chosen based on the discretion of the patient and provider. Patients with HPV infections rarely require emergent management. However, counseling in the ED regarding this distressing condition is relatively common.

s may help reduce viral load but is not a cure. All treatment options are considered equally effective and chosen based on the discretion of the patient and provider. Patients with HPV infections rarely require emergent management. However, counseling in the ED regarding this distressing condition is relatively common. It is important to emphasize that it is common for sexually active people to have HPV at some point in their lives, and most people clear the infection spontaneously. Condoms are protective with HPV , but they are not preventive, and the only way to decrease exposure is to limit the number of sexual partners. It is an incorrect assumption that having HPV indicates an oncogenic certainty or a change in fertility. VIRAL SEXUALLY TRANSMITTED INFECTION TRANSMISSION Numerous viral infections may be transmitted sexually, including HIV , hepatitis B, herpes simplex virus and HPV (discussed earlier), mollus cum contagiosum, and Zika virus.  HUMAN IMMUNODEFICIENCY VIRUS HIV is an RNA retrovirus in the Retroviridae family. HIV infection involves a spectrum of illness, from asymptomatic individuals to those with profound immunosuppression resulting in a wide array of oppor tunistic infections and clinical development of AIDS. The World Health Organization estimates that as of 2016, 36 million people are infected with HIV . 28 Sex with an infected partner is the most common method of transmission of HIV worldwide, but the virus may also be spread parenterally and vertically from mother to child during birth or breastfeeding. In the United States, male-to-male sexual contact is the most common method of transmission, accounting for 78% of new infections, although the incidence of infection in women is rising. 29 In sub-Saharan Africa, where the burden of HIV infection is highest worldwide, heterosexual transmission accounts for most new cases, and mother-to-child transmission remains a significant problem. Acute HIV infection, also called acute retroviral syndrome, causes a mononucleosis-like illness with fever, malaise, headache, sore throat, and sometimes rash and lymphadenopathy. Due to the nonspecific symptoms that resemble many other viral infections, HIV is not usually diagnosed in the acute phase of infection, and affected individuals are unaware of their HIV status. This has important public health implica tions, because the acute infection is when viral shedding and transmissibility is highest. Epidemiologic studies suggest that up to half of all cases of HIV were contracted from persons with acute HIV infection who likely did not know they carried the virus. 31 The clinical manifestations, diagnosis, and treatment of HIV are discussed in detail in Chapter 155, “Human Immunodeficiency Virus Infections. ”  HEPATITIS B The hepatitis B virus may be transmitted sexually, parenterally by blood transfusion or contaminated needles, or vertically from mother to child. Acute hepatitis B may produce acute symptoms, causing a hepatitislike picture with malaise, nausea, vomiting, fever, abdominal pain, and jaundice. Chronic infection develops in 6% to 10% of patients who contract hepatitis B as adults, but a much higher percentage of patients who become infected as children go on to develop chronic hepatitis, Tintinalli_Sec13_p0997-1100.indd 1023 8/2/19 8:12 PM