Editing Sexually Transmitted Infections (section)

=== Infectious ===

==== Epidemiology ====
* In sexually active young US men, genital herpes is most common type of ulcer followed by syphilis
* Chancroid occurs in some parts of the US
* Lymphogranuloma venereum is increasing in incidence in MSM, including in the US.
* Donovanosis/granuloma inguinale is endemic in some tropical and developing areas, including India; Papua, New Guinea; the Caribbean; central Australia; and southern Africa but usually does not occur in the US

==== Diagnosis and Evaluation ====
* '''History and physical exam'''
* '''Labs:'''
** '''Herpes: Culture or NAAT/PCR testing for HSV, and diagnostic serology for determining the specific type of HSV'''
** '''Syphilis: serologic testing and a darkfield examination if possible'''
** '''Chancroid: testing for H. ducreyi should be performed in environments where chancroid is prevalent'''
** '''Patients who are not known to be HIV positive should be tested for HIV'''
** Even after complete diagnostic evaluation, 25% of patients with genital ulcers will have no laboratory-confirmed diagnosis.
* '''Biopsy of ulcers is indicated if they are unusual or do not respond to initial therapy'''

===== Herpes =====
* '''Most common cause of genital ulcers'''
* '''Caused by the herpes simplex virus, a double-stranded DNA virus'''
** '''HSV-1 causes mainly oral infections but now accounts also for 5-30% of first episodes of genital HSV infections'''
** '''HSV-2 causes the majority of genital herpes and is transmitted by sexual contact'''
* Females are more susceptible to HSV-2 infection and are more likely to have symptomatic infections. Most HSV-2 transmission thus occurs from individuals who do not know they are infected
* '''HSV-2 infection seems to protect against HSV-1 infection, but HSV-1 gives only a small amount of protection from infection with HSV-2'''
* '''Pathophysiology'''
** HSV initiates replication in epithelial cells at the site of entry, damages the cells, and enters the ends of peripheral sensory nerves. Once in the nerve cell body, HSV enters a latent state
** Recurrence and reactivation of virus occur with transportation in the peripheral nerves back to the mucosal or skin surface.
*** '''Events that trigger reactivation of HSV include local trauma such as surgery or ultraviolet light, immunosuppression, or fever'''
** '''Incubation period: 4-7 days after sexual intercourse'''
* '''Diagnosis and Evaluation'''
** '''History and Physical Exam'''
*** '''History'''
**** '''Patients have pain, burning, or itching, and 80% of women report dysuria.'''
**** '''Other associated symptoms include flu-like symptoms, fever, headache, malaise, and myalgias.'''
**** '''Possible complications include aseptic meningitis and autonomic dysfunction that can lead to urinary retention'''
*** '''Physical Exam'''
**** '''The classic first presentation of primary herpes is clusters of erythematous papules and vesicles on the external genitalia that do NOT follow a neural distribution'''
**** '''Tender inguinal and femoral lymph nodes may be present.'''
**** '''Over the next 2- 3 weeks, 75% of patients have new lesions, which can progress to vesicles and pustules and can coalesce into ulcers before crusting and healing'''
**** '''Primary genital HSV-1 infection cannot be distinguished from HSV-2 infection on clinical examination alone, but requires laboratory testing.'''
**** Insert figure
*** '''Labs'''
**** '''Options: NAAT or cell culture of a lesion'''
***** '''NAAT is preferred''' due to increased sensitivity, and viral cultures are limited by the rate of viral shedding that can be intermittent and, therefore, cause false-negative results
**** '''While the Tzanck preparation has historically been used, it should not be solely relied upon as it is non-specific and insensitive.'''
**** '''In patients with no active lesions, serology must be used; specific immunoglobulin G (IgG) testing can distinguish the two types of HSV'''
** '''Recurrent episodes'''
*** '''Genital HSV-1 recurs much less frequently than genital HSV-2 infections'''
*** '''HSV recurrences decrease after the first year'''
** '''Management'''
*** '''Treatment for a first clinical episode should be started on clinical grounds before laboratory confirmation of diagnosis.'''
*** '''Currently available medications do not eradicate the virus, but aim to reduce the signs and symptoms of infection and prevent new lesions.'''
**** '''Treatment of recurrent episodes reduces their severity and duration'''.
***** Oral therapy within 24 hours of the first signs or symptoms of recurrence increases the chance of resolving a recurrence without lesions
*** '''Options (3): -clovir'''
***# '''Acyclovir'''
***#* May be needed for those with neurologic complications, those unable to take oral medications, or those with widespread disease (e.g., immunocompromised patients)
***# '''Valacyclovir'''
***# '''Famciclovir'''
*** '''Treatment is usually 7 to 10 days''' but should be extended if lesions are not adequately healed
*** '''Lesions heal in 5-10 days in the absence of antiviral treatment'''

===== Syphilis =====
* '''Caused by Treponema pallidum'''
* '''Primary syphilis'''
** '''Incubation period: typically 2-3 weeks''', can range from 9-90 days for the appearance of lesions after infection
** '''Lesion'''
*** '''Called “chancre”'''
*** Occurs at the initial site of infection
**** In male, lesions are typically on the glans, corona or perineal area
**** In females, lesions are typically on the labia or perianal area
*** '''Usually single and painless''' but can be multiple, and up to 25% of chancres can be painful
**** '''See Figure'''
** '''Local non-tender lymphadenopathy is common'''
** '''Untreated lesions heal spontaneously in 3-8 weeks'''
* '''Secondary syphilis'''
** '''T. pallidum eventually becomes a systemic infection with bacteremia'''.
** '''Appears 3-5 months after the initial infection'''
** '''Characterized by a maculopapular rash, which is often widespread and involves the scalp, palms, and soles of the feet.'''
*** '''The rash can ulcerate and lead to condyloma lata, which are wart-like lesions'''.
** Additional symptoms include fever, malaise, weight loss, patchy alopecia, and ocular inflammation
** A broad vasculitis occurs in ≈10% of patients and may lead to hepatitis, iritis, nephritis, and neurologic problems including headache and cranial nerve involvement, especially VIII (auditory).
** Relapses usually occur in the first year after infection and rarely after the second year. The infection then becomes latent and asymptomatic.
*** Latent syphilis is defined as seroreactivity with no clinical evidence of disease
* Tertiary or late syphilis
** ≈35% of individuals with late latent syphilis will develop the late manifestations of syphilis, which include  neurosyphilis, cardiovascular syphilis, and gummatous syphilis.
* '''Diagnosis and Evaluation'''
** '''Labs'''
*** '''Darkfield examination'''
**** '''Cultures of T. pallidum are not possible'''
**** '''Direct tests include identification of T. pallidum under a dark-ground microscope'''
*** '''Serology'''
**** '''Categories of tests (2):'''
****# '''Non-treponemal''' (directed against phospholipids)
****# '''Treponemal''' (directed against T. pallidum polypeptides)
**** '''Non-treponemal'''
***** '''Includes:'''
****** '''Rapid plasma reagin (RPR) test'''
****** '''Venereal Disease Research Laboratory (VDRL) test'''
****** '''Toluidine red unheated serum test (TRUST)'''
***** '''Need confirmation with a treponemal test because they can be positive in other conditions such as:'''
****** '''Viral infections'''
****** '''Pregnancy'''
****** '''Malignancies'''
****** '''Autoimmune disease'''
****** '''Advanced age'''
***** '''Used to monitor disease activity'''
**** '''Treponemal tests'''
***** Includes
****** '''FTA-ABS:''' fluorescent treponemal antibody absorption test
****** '''MHA-TP:''' microhemagglutination assay for T. pallidum
****** '''TP-HA:''' T. pallidum hemagglutination assay
****** '''TP-PA:''' T. pallidum particle agglutination test
*** All patients with syphilis should be tested for HIV
* '''Management'''
** '''Antibiotics'''
*** '''Standard treatment for all stages of syphilis is benzathine penicillin G'''
**** Stage and clinical manifestations of syphilis determine the preparation, dosage, and length of treatment
*** '''Jarisch-Herxheimer reaction'''
**** '''Not an allergic reaction to penicillin but occurs with treatment of the treponemes, and more commonly with treatment with penicillin and in early syphilis.'''
**** '''Consists of fever, malaise, nausea, and vomiting;''' may also be associated with chills and exacerbation of secondary rash.
**** '''Management'''
***** '''Bed rest and nonsteroidal anti-inflammatory medications.'''

===== Chancroid =====
* '''Caused by H. ducreyi (gram-negative coccobacilli)'''
* '''Initial presentation of a papule that may progress to anogenital painful ulceration and lymphadenitis with progression to bubo formation'''
* '''Incubation period: 3-10 days'''
* Most common site of infection: prepuce
* '''Diagnosis and Evaluation'''
** '''Labs'''
*** '''Definitive diagnosis requires culture on media not routinely available.'''
*** '''Centers for Disease Control and Prevention suggests that a probable diagnosis of chancroid can be made if''':
***# The patient has one or more painful ulcers
***# No evidence of T. pallidum is present on darkfield examination of ulcers or by serologic testing for syphilis performed at least 7 days after onset of the ulcers
***# Ulcers and lymphadenopathy, if present, are typical for chancroid
***# Results of tests for HSV on the ulcer exudate are negative
*** Chancroid, like genital herpes and syphilis, is a risk factor for transmission of HIV; patients should be tested for HIV at the time of diagnosis of chancroid
* '''Management'''
** '''Options:'''
**# '''Azithromycin 1g in a single dose or'''
**# '''Ceftriaxone 250 mg IM in single dose''' or
**# Ciprofloxacin 500 mg orally BID x 3 days or
**# Erythromycin base 500 mg orally TID x 7 days

===== Lymphogranuloma venereum =====
* '''Caused by chlamydia'''
* '''A self-limited genital ulcer or papule is sometimes 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'''
** Inguinal lymphadenopathy are more common in males because the lymph drainage of the cervix and vagina are to the retroperitoneal rather than the inguinal lymph nodes
* Lymphogranuloma venereum proctocolitis can mimic inflammatory bowel disease, and complications include chronic colorectal fistulas and strictures
* '''Diagnosis and Evaluation'''
** '''Labs'''
*** '''Swab of lesions or aspiration of buboes from genitals or lymph node''', sent for culture, direct immunofluorescence, '''or nucleic acid detection'''
* '''Management'''
** '''Doxycycline''' 100 mg orally BID x 21 days

===== Donovanosis/Granuloma inguinale =====
* '''Caused Klebsiella granulomatis''' (intracellular gram-negative bacterium)
* '''Does not usually occur in the US'''
* '''The disease manifests as painless, slowly progressive ulcers on the genitals and perineum. Despite the name, inguinal involvement is uncommon (10%), but tender if present'''
* '''Lesions'''
** '''Described as beefy red because of high vascularity, and they bleed easily'''
** Insert figure

*'''Diagnosis and Evaluation'''
** '''Labs'''
*** '''Requires visualization of''' dark-staining '''Donovan bodies''' on crush preparation or biopsy
*'''Management'''
** '''Doxycycline''' 100 mg PI BID for at least 3 weeks and until all lesions have healed