Campbell-Walsh Urology, 11th Edition

PART III

Infections and Inflammation

15

Sexually Transmitted Diseases

Michel Arthur Pontari

Questions

  1. The most commonly diagnosed bacterial sexually transmitted infection (STI) in the United States is:
  2. gonorrhea.
  3. ureaplasma.
  4. syphilis.
  5. chlamydia.
  6. chancroid.
  7. The major health risk to untreated Chlamydiainfection in men is:
  8. epididymitis.
  9. Reiter syndrome.
  10. orchitis.
  11. chronic prostatitis/chronic pelvic pain syndrome.
  12. transmission to a female partner resulting in pelvic inflammatory disease.
  13. In addition to treatment for chlamydia, what other medication is recommended as a first-line treatment for gonorrhea?
  14. Ciprofloxacin
  15. Levofloxacin
  16. Ceftriaxone
  17. Cefixime
  18. Penicillin VK
  19. Which subtypes of human papillomavirus (HPV) are responsible for development of malignancies including cervical, penile, and anal?
  20. 16 and 18
  21. 13 and 14
  22. 6 and 11
  23. 31 and 33
  24. 26 and 28
  25. HPV vaccines are indicated for which groups?
  26. All sexually active women
  27. All sexually active men who have sex with men (MSMs)
  28. Men and women up to age 26 years
  29. Only women up to age 26 years
  30. Only women with a family history of cervical cancer
  31. Which STI often has no visible genital lesion because it has usually resolved by the time of presentation and is associated with tender, often suppurative adenopathy?
  32. Chancroid
  33. Herpes simplex virus type 2 (HSV-2)
  34. Herpes simplex virus type 1 (HSV-1)
  35. Donavanosis
  36. Lymphogranuloma venereum
  37. Which of the following is not a reportable STI in every state?
  38. HSV
  39. Syphilis
  40. Chancroid
  41. Chlamydia
  42. Human immunodeficiency virus (HIV)
  43. Which of the following tests should be used to monitor the clinical response to treatment in patients with syphilis?
  44. Treponema pallidumparticle agglutination (TP-PA)
  45. Rapid plasma reagin (RPR)
  46. Fluorescent treponemal antibody absorption (FTA-ABS)
  47. Darkfield microscopy
  48. Tzanck test
  49. What is the treatment of choice for primary, secondary, and early latent syphilis?
  50. Azithromycin
  51. Benzathine penicillin
  52. Probenecid penicillin
  53. Ceftriaxone
  54. Procaine penicillin
  55. Which statement is true regarding the likelihood of recurrent genital lesions in patients with HSV-1 and HSV-2?
  56. No difference except in HIV patients in whom HSV-1 recurs more often
  57. No difference except in HIV patients in whom HSV-2 recurs more often
  58. HSV-1 recurs more often
  59. HSV-2 recurs more often
  60. No difference
  61. What is the causative organism for lymphogranuloma venereum?
  62. Calymmatobacterium
  63. Klebsiella
  64. Chlamydia
  65. Haemophilus ducreyi
  66. Trichomonas
  67. Gardasil in males is recommended:
  68. to prevent transmission of HPV to their partners.
  69. only for persons with documented HPV.
  70. to prevent anal cancer and genital warts.
  71. to prevent genital warts only.
  72. only in men older than 26 years.
  73. Donovan bodies are seen on:
  74. Thayer-Martin medium in gonorrhea.
  75. ulcer scraping in primary syphilis.
  76. biopsy of condyloma acuminata.
  77. lymph node aspiration in lymphogranuloma venereum.
  78. biopsy of ulcer in granuloma inguinale.
  79. Clue cells are diagnostic of:
  80. Bacterial vaginosis (BV).
  81. Trichomonas.
  82. Scabies.
  83. Candidavulvovaginitis.
  84. Torulopsis glabratavulvovaginitis.
  85. HIV is what type of virus?
  86. Single-stranded RNA
  87. Double-stranded RNA
  88. Single-stranded messenger RNA (mRNA)
  89. Single-stranded DNA
  90. Double-stranded DNA
  91. The HIV envelope precursor protein gp160 is cleaved into what two envelope proteins?
  92. gp 123 and gp33
  93. gp 124 and gp40
  94. gp 141 and gp 20
  95. gp 120 and gp41
  96. gp 120 and gp6
  97. HIV infects which immune cells?
  98. Macrophages
  99. B cells
  100. CD4 T cells
  101. CD8 T cells
  102. Natural killer (NK) cells
  103. The initial screening test for HIV is:
  104. Western blot.
  105. indirect immunofluorescence assay.
  106. nucleoside amplification assay.
  107. rapid enzyme immunoassay (EIA).
  108. viral culture.
  109. Antiretroviral therapy is recommended for:
  110. patients with CD4 count of < 200 only.
  111. patients with CD4 count of < 350 only.
  112. patients with CD4 count of < 500 only.
  113. patients with CD4 count of < 500 and symptoms.
  114. all patients with HIV.
  115. What factor is not associated with increased risk of seroconversion with HIV after a needle stick?
  116. Recent infection by patient
  117. Deep exposure of needle
  118. Visible blood on injuring device
  119. Prior placement of injuring device in artery or vein
  120. Patient dying within 2 months of exposure
  121. Polymorphisms of which gene are associated with development of HIV-associated nephropathy (HIVAN) in African-American patients?
  122. Tyrosine kinase
  123. Antichymotrypsin-1
  124. Apolipoprotein-1
  125. Tumor necrosis alpha
  126. Interleukin-10
  127. Which type of antiretroviral medications are associated with formation of urinary tract stones?
  128. Integrase inhibitors
  129. Fusion inhibitors
  130. Protease inhibitors
  131. Non-nucleoside reverse-transcriptase inhibitors (NNRTIs)
  132. CCR5 blockers
  133. What is the best diagnostic test to detect HIV in the acute phase of infection?
  134. Indirect immunofluorescence assay
  135. Viral load assay
  136. Western blot
  137. HIV-1/HIV-2 serology assay
  138. Rapid enzyme immunoassay
  139. What class of medication can have a prolonged half-life when used in association with protease inhibitors and NNRTI's for treatment of HIV?
  140. Alpha-blockers
  141. 5-alpha reductase inhibitors
  142. Beta-3 agonists
  143. PDE5 inhibitors
  144. Fluoroquinolones
  145. What type of genitourinary (GU) cancer is not increased in frequency in patients with HIV?
  146. Prostate cancer
  147. Kidney cancer
  148. Penile cancer
  149. Testis cancer
  150. Kaposi sarcoma

Pathology

  1. A 32-year-old sexually active woman has the lesion in Figure 15-1A and Bexcised from her vulva. The diagnosis is condyloma acuminata. The most appropriate next step is:

FIGURE 15-1A AND B (From Bostwick DG, Cheng L. Urologic surgical pathology. 3rd ed. St. Louis: Saunders; 2014.)

  1. acetic acid test.
  2. podophyllin to the base of the lesion.
  3. HPV vaccine.
  4. vaginoscopy.
  5. cystoscopy.
  6. A 22-year-old sexually active man has a 2-mm raised red lesion in the suprapubic area. A biopsy is performed (depicted in Figure 15-2) and read as molluscum contagiosum. The patient is concerned and desires treatment. The most appropriate treatment is:

FIGURE 15-2 (From Bostwick DG, Cheng L. Urologic surgical pathology. 3rd ed. St. Louis: Saunders; 2014.)

  1. wide local excision.
  2. 5-Fluorouracil cream.
  3. Ciprofloxacin for 2 weeks.
  4. Bactrim for 4 weeks.
  5. Liquid nitrogen application.

Answers

  1. d. Chlamydia. Chlamydiais the most common bacterial STI in the United States. The 1,422,976 cases of Chlamydia trachomatis infection reported to the Centers for Disease Control and Prevention (CDC) in 2012 was the largest number ever reported to the CDC for any condition. The second most common bacterial STI is gonorrhea.
  2. e. Transmission to a female partner resulting in pelvic inflammatory disease.Up to 75% of women with chlamydial infection can be asymptomatic. Ascending chlamydial infection can result in scarring of the fallopian tubes, pelvic inflammatory disease, risk for ectopic pregnancy, pelvic pain, and infertility. The risk of untreated chlamydial infection producing pelvic inflammatory disease is estimated to be between 9.5% and 27% of cases.
  3. c. Ceftriaxone.As of 2007, quinolones are no longer recommended in the United States for treatment of gonorrhea and associated conditions such as pelvic inflammatory disease. As of August 2012, because of high resistance, cefixime is no longer recommended as first-line therapy to treat gonorrhea. Current treatment of uncomplicated gonococcal infections of the cervix, urethra, and rectum are ceftriaxone, 250 mg IM, single dose PLUS azithromycin, 1 g orally in single dose, or doxycycline, 100 mg orally twice per day for 7 days.
  4. a. 16 and 18.Types 6 and 11 are nononcogenic and are responsible for about 90% of anogenital warts. Other subtypes including 16 and 18 account for cervical cancer, and other types of anogenital cancer including vulvar, vaginal, anal, and penile.
  5. c. Men and women up to age 26 years.In June 2006, a quadrivalent HPV vaccine (Gardasil; Merck, Sharpe, and Dohme Corporation) was licensed for use in the United States in females aged 9 to 26 years. In October 2009, this vaccine also was licensed for use in males aged 9 to 26 years. This vaccine provides protection against HPV types 6, 11, 16, and 18. In October 2009, a bivalent HPV vaccine (Cervarix; Glaxo SmithKline Biologicals, Research Triangle Park, NC) that provides protection against types 16 and 18 was licensed for use in females aged 10 to 25 years.
  6. e. Lymphogranuloma venereum.A self-limited genital ulcer or papule sometimes is present at the site of infection but usually has disappeared by the time of presentation. The secondary stage is the most common presentation in heterosexuals and is marked by tender inguinal and/or femoral lymphadenopathy, typically unilateral.
  7. a. HSV.Diseases that must be reported to local health authorities: Syphilis, gonorrhea, chlamydia, chancroid, HIV infection, and acquired immunodeficiency syndrome (AIDS) are reportable diseases in every state.
  8. b. RPR. Nontreponemal tests (RPR or VDRL) are used to monitor disease activity.A fourfold change in titer equivalent to a change of 2 dilutions (e.g., from 1:16 to 1:4) is considered necessary to demonstrate a clinically significant difference.
  9. b. Benzathine penicillin.Benzathine penicillin is the treatment of choice for all of the stages of syphilis. Treatment varies by dose and duration of therapy. Not considered appropriate treatments are combinations of benzathine and procaine penicillin (Bicillin C-R), or oral penicillin.
  10. d. HSV-2 recurs more often.Genital HSV-1 recurs much less frequently (0.02 per month) than genital HSV-2 infections (0.23 per month), on the order of 10-fold less.
  11. c. Chlamydia.Lymphogranuloma venereum (LGV) is an infection by Chlamydia, specifically serovars L1, L2, or L3.
  12. c. To prevent anal cancer and genital warts.The quadrivalent vaccine is used in males to prevent genital warts and in both genders to prevent anal cancer. MSMs are particularly at risk for developing anal intraepithelial neoplasia and anal cancer. As in women, it is best started in males before the onset of sexual activity.
  13. e. Biopsy of ulcer in granuloma inguinale.Granuloma inguinale (GI) is an infection by the intracellular gram-negative bacterium Klebsiella granulomatis (formerly called Calymmatobacterium granulomatis) that produces genital ulcers. The bacterium is a strict human pathogen, which makes culture difficult. Diagnosis requires visualization of dark-staining Donovan bodies on crush preparation or biopsy, described by Donovan in 1905. These are intracellular inclusions of the bacteria within the cytoplasm of macrophages and appear deep purple when stained with a Wright, Giemsa, or Leishman stain.
  14. a. Bacterial vaginosis (BV). Characteristic findings for BV on microscopic exam are clue cells, which are vaginal epithelial cells covered with bacteria.
  15. a. Single-stranded RNA.The genetic material in HIV is single-stranded RNA. After entry into the targeted cell, the RNA is reverse transcribed by a reverse transcriptase into a double-stranded DNA. This new DNA is assembled into complexes, which then associate with the target cell chromatin and integrate via the action of viral integrase. The cell then translates and transcribes the viral genes to produce proteins that will assemble new copies of the virus. Copies of the virus are called virions.
  16. d. gp 120 and gp41.The virus is shaped like a sphere. It is covered by an outer envelope that is a lipid bilayer derived from the host cell when it buds out of the cell. Embedded in the envelope is a complex of proteins known as Env. There is initially a precursor gp160 that is cleaved by a protease in the trans-Golgi network. It is cleaved into an outer subunit glycoprotein 120 (gp120) and a transmembrane subunit glycoprotein 41 (gp41). After proteolysis, the gp120 and gp41 remain coupled as noncovalent heterodimers.
  17. c. CD4 T cells.Glycoprotein gp120 has a high-affinity binding site for the T lymphocyte receptor CD4.
  18. d. Rapid enzyme immunoassay (EIA).Diagnosis of HIV includes the use of serologic tests that detect antibodies against HIV-1 (and HIV-2) and by virologic tests that detect HIV antigens RNA. The initial test is a screening test for antibodies, the conventional or rapid EIA. The initial result can be obtained in 30 minutes. Positive or reactive screening tests must be confirmed by a supplemental antibody test, Western blot, and indirect immunofluorescence assay (IFA) or by a virologic test, the HIV-1 RNA assay.
  19. e. All patients with HIV.The benefit of treatment may depend on the starting CD4 count, but treatment guidelines recommend treatment for all patients regardless of CD4 count.
  20. a. Recent infection by patient.A review of factors for increased risk of infection done by the CDC identified four that increased risk: deep as opposed to superficial exposure (odds ratio [OR] 15, 95% confidence index [CI] 6-41), visible blood on the injuring device (OR 6.2, 95% CI 2.2-21), prior placement of the injuring device in an artery or vein (OR 4.3, 95% CI 1.7-12), and patient dying within 2 months of the exposure (preterminal disease) (OR 5.6, 95% CI 2-16). Recent infection by the patient was not associated with an increased risk of seroconversion.
  21. c. Apolipoprotein-1.African-Americans carrying two variants of the APOL-1 gene are at very high risk for HIVAN. These genes encode a secreted lipid binding protein called apolipoprotein-1 (apoL1). The variants G1 and G2 are common in African chromosomes but absent in European chromosomes; these variants lyse trypanosomes, including Trypanosoma brucei rhodesiense, which causes African sleeping sickness. Thus, these loci are thought to be selected out in this population. The presence of these two genes together increases the risk 29-fold, resulting in a 50% risk of developing HIVAN in untreated individuals as compared with a 12% baseline risk. Focal segmental glomerulosclerosis (FSGS) found in individuals with the two risk genes also occurs at an earlier age and progresses much more rapidly.
  22. c. Protease inhibitors.The protease inhibitors specifically have the possibility of stone formation. Indinavir can form crystals in the urine. Indinavir stones are typically radiolucent on both plain film and computed tomography scan but can also be mixed with calcium and appear radio-opaque. Newer inhibitors including lopinavir, atazanavir, amprenavir, and nelfinavir have also been associated with the development of stones, but with less frequency than reported for indinavir.
  23. b. Viral load assay.During this initial 3-month period, the “window” period, antibody screening tests may be negative but the person still infected. Virologic tests for HIV-1 RNA can be used to detect an acute infection in persons negative for HIV antibodies.
  24. d. PDE5 inhibitors.PDE5 inhibitors depend on CYP3A for clearance, and all protease inhibitors and NNRTIs are inhibitors of CYP3A to some extent. This can lead to a significant increase in the serum dose of PDE5 inhibitors, and therefore they should be started at the lowest dose possible in patients on these antiretroviral medications.
  25. a. Prostate cancer.The relative risk of prostate cancer in men with HIV compared to uninfected individuals has been reported as either no different or even less at 0.70.

Pathology

  1. d. Vaginoscopy.The figure shows marked papillomatosis with koilocytic atypia. The patient should have a thorough genital examination, including vaginoscopy for other lesions.
  2. e. Liquid nitrogen application.The biopsy shows an epidermal crater filled with molluscum bodies. This is usually a self-limited disease and requires no treatment. If treatment is desired, a local therapy is appropriate, such as curettage or liquid nitrogen application.

Chapter review

  1. When exposed to STIs, women are more likely to become infected and less likely to be symptomatic.
  2. Chlamydia is the most common sexually transmitted disease in the United States.
  3. Herpes simplex virus type 2 accounts for 90% of the genital herpes infections. Herpes simplex virus type 1 accounts for the remainder and is the common cause of cold sores; silent infection is common in this disease. The diagnosis is made by viral culture and subtyping. HSV enters the nerve and remains latent in the nerve cell body. It may cause aseptic meningitis and autonomic dysfunction, which may lead to urinary retention.
  4. Chancroid is caused by Haemophilus ducreyiand results in a painful, nonindurated ulcer covered by an exudate. Inguinal adenopathy occurs and may become suppurative.
  5. Chancre of syphilis is single, painless, indurated, and clean. It is associated with nontender inguinal lymphadenopathy.
  6. Latent syphilis is seropositive with no evidence of disease. Early latent syphilis occurs in less than 1 year. Late latent syphilis occurs beyond 1 year.
  7. Primary syphilis is the acute infection. Secondary syphilis is manifested by mucocutaneous and constitutional signs and symptoms that are often associated with a maculopapular rash. Tertiary syphilis is a systemic disease involving the cardiovascular, skeletal, and central nervous system.
  8. Treponemal tests for syphilis are generally positive for life and do not indicate treatment response. RPR, Venereal Disease Research Laboratory (VDRL), and the toluidine red unheated serum test (TRUST) are nontreponemal tests and correlate with disease activity. They usually become negative after treatment. Nontreponemal tests (RPR or VDRL) are used to monitor disease activity.
  9. The Jarisch-Herxheimer reaction occurs when patients with syphilis are treated with penicillin, resulting in the release of toxic products when the treponemes are killed. The symptoms include headache, myalgia, fever, tachycardia, and increased respiratory rate.
  10. Lymphogranuloma venereum presents as a single painless ulcer and painful inguinal adenopathy. Lymphogranuloma venereum is marked by tender inguinal and/or femoral lymphadenopathy, typically unilateral.
  11. Polymerase chain reaction (PCR) assays are used for diagnosing chlamydial infection.
  12. A strawberry rash on the vulva or strawberry cervix is seen in trichomoniasis.
  13. More than 99% of cervical cancers and 84% of anal cancers are associated with HPV 16 or 18. The most common serotype associated with squamous cell carcinoma of the penis is HPV 16.
  14. Biopsies of genital warts are not routinely indicated but should be performed when the wart is atypical, pigmented, indurated, or fixed and ulcerated.
  15. HPV vaccine is recommended for females age 9 to 26 years and may also be given to males of the same age range.
  16. The presence of sexually transmitted infections increases the risk for concurrent HIV.
  17. Ulcerative sexually transmitted infections including herpes, syphilis, and chancroid enhance the susceptibility to HIV per sexual contact.
  18. Antiviral therapy for HIV does not necessarily make the patient noninfectious.
  19. Men who are circumcised are at lower risk for HIV infection.
  20. There are two types of HIV viruses: HIV-1 and HIV-2. There are very few cases of HIV-2 in the developed world, and it is less easily transmitted and less virulent than HIV-1.
  21. HIV is a retrovirus that infects T cells and dendritic cells.
  22. Antiretroviral combination therapy delays the rate of progression of the disease and prolongs survival.
  23. Overt AIDS is marked by a low CD4 + T-cell count.
  24. Plasma HIV RNA load is the most accurate predictor of disease progression.
  25. The diagnosis of HIV is made by screening for anti-HIV-1 and anti-HIV-2 antibodies. If this is positive, confirmation is made by using Western blot analysis. After treatment, the nadir of plasma HIV RNA predicts long-term outcome.
  26. HIV testing is recommended for anyone diagnosed with a sexually transmitted infection or at risk for sexually transmitted infections.
  27. Herpes simplex virus increases HIV replication in persons infected with both viruses.
  28. Human papillomavirus infection increases the risk for carcinoma, especially in HIV-infected hosts.
  29. The most common intrascrotal pathologic process in AIDS patients is testicular atrophy.
  30. Voiding dysfunction is common in patients with advanced HIV infection.
  31. Urinary calculi have been associated with, most notably, protease inhibitors such as indinavir. These stones are soluble at an acidic pH.
  32. HIV-associated nephropathy is a glomerular disease that often presents as proteinuria.
  33. Patients with HIV are at particular increased risk for Kaposi sarcoma and non-Hodgkin lymphoma. Kaposi sarcoma presents as a raised, firm, indurated purplish plaque, reflecting the presence of abundant blood vessels, extravasated erythrocytes, and siderophages.
  34. Human herpesvirus 8 is essential for all forms of Kaposi sarcoma.
  35. HIV protease inhibitors are also potent antiangiogenic molecules and are useful in treating Kaposi sarcoma. However, localized lesions may be treated by irradiation, laser, cryotherapy, or intralesional injections of antineoplastic drugs. Corticosteroids should not be used to treat the lesions.
  36. There is an increased incidence of Kaposi sarcoma, non-Hodgkin lymphoma, and cervical cancer in patients with HIV infection. There also appears to be an increased incidence of the following GU tumors: testicular, renal, and penile.
  37. The risk of untreated chlamydial infection producing pelvic inflammatory disease is estimated to be between 9.5% and 27% of cases.
  38. Current treatment of uncomplicated gonococcal infections of the cervix, urethra, and rectum are ceftriaxone 250 mg IM single dose PLUS azithromycin, 1 g orally in single dose or doxycycline, 100 mg orally twice per day for 7 days.
  39. Donovan bodies noted in granuloma inguinale are intracellular inclusions of the bacteria within the cytoplasm of macrophages and appear deep purple when stained with a Wright, Giemsa, or Leishman stain.
  40. Characteristic findings for bacterial vaginosis on microscopic exam are clue cells, which are vaginal epithelial cells covered with bacteria.
  41. Factors that increase the risk for transmitting HIV include deep as opposed to superficial exposure (OR 15, 95% CI 6-41), visible blood on the injuring device (OR 6.2, 95% CI 2.2-21), prior placement of the injuring device in an artery or vein (OR 4.3, 95% CI 1.7-12), and patient dying within 2 months of the exposure (preterminal disease) (OR 5.6, 95% CI 2-16).
  42. PDE5 inhibitors depend on CYP3A for clearance, and all protease inhibitors and NNRTIs are inhibitors of CYP3A to some extent. This can lead to a significant increase in the serum dose of PDE5 inhibitors, and therefore they should be started at the lowest possible dose in patients on these antiretroviral medications.