[STDs] Atlas of Genital Herpes Disease

These are the images, diagnosis and treatment of the disease caused byGenital Herpes. This is a Viral Sexually Transmitted Diseases.

Genital Herpes

Genital herpes is the most common cause of genital ulceration in most countries, with an estimated incidence in the United States up to one million cases per year and a prevalence of 50 to 60 million persons. Most cases of recurrent genital herpes are caused by herpes simplex virus type 2 (HSV-2), but up to half of all initial genital infections are due to HSV type 1 (HSV-1), the usual cause of orolabial herpes. Infection with either HSV type is lifelong, with virus persisting in neural tissue, especially the cranial or dorsal spinal nerve root ganglia, and at infected mucocutaneous sites. The presence of specific antibody denotes current infection and the potential for clinical recurrences, subclinical viral shedding, and transmission to sex partners. HSV infections have long been viewed as mostly latent with relatively infrequent reactivation. However, recent research shows unapparent viral replication to be much more frequent than previously understood, and herpes is more accurately characterized as a continuously active infection than a recurrent one.

Both symptomatic and asymptomatic recurrences are substantially more frequent for genital HSV-2 than for genital or oral HSV-1. Almost all genital HSV-2 infections are acquired by genital or anal intercourse, whereas most genital HSV-1 infections are acquired by orogenital exposure. Because of the reduced recurrence frequency, genital to genital HSV-1 transmission probably is uncommon. Therefore, HSV-2 seroprevalence in a population accurately denotes genital infection, whereas HSV-1 antibody reflects orolabial infection plus a substantial (albeit unquantified) proportion with genital herpes. Owing to varied clinical manifestations, complexity of diagnosis, multiple treatment options, multifaceted prevention strategies, and the need for sophisticated counseling, the clinical management of genital herpes is more complex than that of any STD except HIV/AIDS.

Most genital HSV infections are subclinical, but many apparently asymptomatic persons have mild or nonspecific symptoms whose significance is not understood until infection is suspected by transmission to a partner or through serological testing. No cure exists, but therapy with acyclovir and related drugs accelerates healing of lesions and reduces the frequencies of recurrent outbreaks, asymptomatic reactivation, and sexual transmission of HSV-2. The most common serious complication is perinatal transmission resulting in neonatal herpes, which often is fatal or causes permanent neurodevelopmental. sequelae. Other biomedical complications in adults include meningitis (primarily HSV-2), encephalitis (mostly due to HSV-1), aggressive and persistent mucocutaneous ulceration in persons with AIDS or other immune deficiencies, erythema multiforme, Stevens Johnson syndrome, and rare cases of systemic dissemination with hepatic necrosis which often is fatal. Herpetic whitlow and keratoconjunctivitis can result from auto-inoculation during initial and less commonly during recurrent herpes. The psychological impact of genital herpes also can be substantial, primarily resulting from fear of transmission to sex partners.

As for all inflammatory STDs, HSV-2 infection (but apparently not HSV-1, whether oral or genital) is associated with enhanced sexual acquisition of HIV, even when asymptomatic. Owing to the high prevalence of HSV-2 in almost all populations at risk for HIV, genital herpes has greater populationlevel impact on HIV transmission than all other STDs, accounting for up to half of all HIV infections worldwide. Unfortunately, however, treatment of HSV-2 infected persons with acyclovir does not reduce the risk of HIV infection. At least part of the explanation appears to be frequent viral replication and a subclinical inflammatory response that persist at mucosal and cutaneous sites of recurrent outbreaks regardless of antiviral therapy, which includes activated lymphocytes and dendritic cells that are especially susceptible to HIV.

The priority that should be accorded prevention efforts against genital and neonatal herpes is controversial, as is serological screening for HSV-2 in persons at risk. However, there is no debate about the diagnostic utility of HSV type-specific serological tests or viral detection by culture or polymerase chain reaction (PCR) in patients with genital herpes or genital ulcer disease. Virus type should be determined in all patients with genital herpes, because of the differences between genital HSV-1 and HSV-2 infection in clinical course, the potential for sexual transmission, and susceptibility to HIV.

EPIDEMIOLOGY

Incidence and Prevalence

• National seroprevalence of HSV-2 antibody in 14- to 49-year-old U.S. residents was 16% in 2005–2008, stable since 2001–2004 (17%)

• About 45 million persons in the United States are infected with HSV-2; the total with genital herpes, including HSV-1, probably exceeds 60 million

• Initial visits to physicians for genital herpes rose from ~100,000 per year in 1970s to ~300,000 annually in 2006–2009

• In western Europe, HSV-2 seroprevalence is generally lower than in United States; 10–15% in most

countries

• HSV-2 seroprevalence is >50% in many developing countries

• HSV-1 seroprevalence (mostly reflecting orolabial infection) is 50–90% in adults in most countries

Transmission

• Requires direct contact with infected tissues or secretions

• Most genital infections are acquired from partners with subclinical infection

• Prior infection apparently confers resistance, if not complete immunity, to reinfection with the same HSV type at any anatomic location

° Superinfections with same virus type uncommon

° Mutually infected sexually active couples do not reinfect one another

• Autoinoculation can result in herpetic whitlow or keratoconjunctivitis

° Mostly during primary infections

° Rare in persons with longstanding, recurrent herpes

• No documented transmission by fomites, shared clothing or towels, or environmental exposure (e.g.,

toilets), notwithstanding occasional assertions by patients or face-saving explanations by naïve clinicians

• Perinatal transmission to newborns, especially following new infection in late pregnancy

Age

• In the United States in 2005–2008, HSV-2 seroprevalence was 1% at age 14–19, 10.5% at age 20–29,

20% at age 30–39, 26% at age 40–49

• All ages are susceptible, but in the United States genital HSV-2 is acquired most frequently by persons

age 25–35 years

Sex

• Women are more susceptible to genital HSV than men, owing to larger surface area exposed and

increased mucosal exposure

• National seroprevalence of HSV-2 in the United States in 2005–2008 was 21% in women, 12%

in men

Sexual Orientation

• MSM generally higher HSV-2 seroprevalence than age-comparable heterosexual men (e.g. 25–30%)

Other Risk Factors

• Race/ethnicity: HSV-2 seroprevalence in the United States during 2005–2008:

° African Americans, 39%

° Whites, 12%

° Mexican Americans, 10%

• Independent of race, HSV-2 and HSV-1 prevalences are highest in lower socioeconomic populations

CLINICAL CLASSIFICATION

Primary Genital Herpes

• Definition: Patient’s first infection with either HSV type

• Seronegative at onset for both HSV-1 and HSV-2

• Symptomatic cases commonly are severe, often prolonged (3–4 weeks) if untreated

• Frequent mucosal involvement (e.g., cervicitis, urethritis), regional lymphadenopathy, regional neuropathy, fever, headache, malaise

• Up to 50% of cases due to HSV-1, acquired primarily by orogenital exposure

Initial Nonprimary Genital Herpes

• Definition: Initial infection in persons with prior infection with opposite HSV type; usually newly acquired HSV-2 in persons seropositive for HSV-1

• Systemic manifestations uncommon

• About 40% of apparent initial cases actually are the first-recognized recurrent outbreaks of HSV-2 in persons with longstanding infection; i.e., patient is seropositive to HSV-2 at onset

Recurrent Genital Herpes

• Definition: Second or subsequent outbreak due to same virus type

• Genital HSV-1 reactivates less frequently than HSV-2

• Most episodes clinically mild and briefer than initial herpes

• Cervicitis, urethritis, lymphadenopathy, neuropathy, and systemic manifestations can occur but are uncommon

Subclinical Infection

• Most genital HSV infections are subclinical, including primary, nonprimary initial, or recurrent herpes

• Includes truly asymptomatic and symptomatic but unrecognized infection

• In genital HSV-2, the virus can be detected by culture 2–7% of asymptomatic days in first 6– 12 months after symptomatic initial herpes, 1–3% of days thereafter

• Using PCR testing 4 times daily, patients with genital HSV-2 have a mean of 18 reactivations per year, often lasting <24 hours, mostly asymptomatic; some patients have >100 reactivations per year; some reactivations last 6 hours or less.

HISTORY

Incubation Period

• Usually 3–5 days for symptomatic initial herpes, sometimes 10 days, rarely up to 3 weeks

Symptoms

Primary Genital Herpes

• Multiple genital or perianal lesions, usually widely spaced and bilateral

• Vaginal discharge is common

• Urethral discharge is common in men, usually with severe dysuria

• Cutaneous lesions evolve over 7–15 days from papule, to vesicle, to pustule, to ulcer, to crust

• Lesions on mucosal and moist surfaces (e.g., vaginal introitus, labia minor, urethra, under foreskin,

rectum) ulcerate early, often with severe pain, and do not crust

• Repeated crops of lesions may appear over 2–6 weeks

• Infections acquired by receptive anal sex can have rectal pain, discharge, tenesmus, and other symptoms of proctitis (see Chap. 21)

• Often inguinal pain and swelling, usually bilateral

• Often neuropathic symptoms referable to sacral nerve roots, e.g., urinary retention, constipation, paresthesias

• Fever, malaise, headache often present; occasionally photophobia, stiff neck

First Episode Nonprimary Genital Herpes

• Usually fewer lesions than primary herpes

• Untreated duration typically 10–20 days

• Inguinal pain and swelling less common than in primary infection

• Genital discharge, dysuria, and systemic and neuropathic symptoms may occur but less commonly and often less severe than primary herpes

Recurrent Genital Herpes

• Usually clusters of few (2–10) lesions, lateralized to one side of midline

• Repeat outbreaks often recur within 2–3 cm of same location, but exceptions, i.e., recurrences in multiple locations, are common

• Following symptomatic initial infection, mean 4–5 outbreaks annually in first 1–2 years; 40% of patients have >6 and 20% have >10 outbreaks in first year

• Genital HSV-1 causes fewer symptomatic recurrences; in first 1–2 years, 40% have no symptomatic outbreaks, and 40% have only 1 or 2 recurrences

• Most recurrent outbreaks occur on genitals or perianally, but some persons have nongenital outbreaks such as buttock, upper thigh, lower abdomen (“boxer shorts” area)

• Atypical ulcerative lesions are common, i.e., without recognized vesicular or pustular stage

• Neurologic prodome commonly precedes recurrent outbreaks by 1–2 days; typically paresthesias (“tingling”, “burning”) or hypesthesia where lesions occur or in concordant sacral nerve distribution

• Neuropathic symptoms rare other than prodrome

• Inguinal swelling and systemic symptoms rare

• Debilitating, erosive ulcers are common in persons with HIV infection or other immunodeficiency

• CNS reactivation of HSV-2 is the main cause of the rare syndrome of recurrent aseptic meningitis (Mollaret meningitis, “benign recurrent lymphocytic meningitis”).

PHYSICAL EXAMINATION

• Genital HSV-1 and HSV-2 infections are clinically indistinguishable, except for differing frequencies of reactivation

• Initial genital herpes, especially primary, usually presents with multiple nonclustered lesions, bilaterally distributed

• Usual sites in initial herpes are those that receive maximum friction during sex, i.e., penis, introitus, labia minora, anus; less common on scrotum, labia majora, pubic area, or buttocks

• Erythematous papules, vesicles, pustules, ulcers, or crusts • Evolution from initial papule to crust and healing typically requires 10–15 days for initial herpes,7–10 days for reactivations

• Recurrent lesions typically occur in clusters, but single lesions are common

• Recurrent lesion locations:

° Usually genitals (penis, introitus, labia, vulva) or perigenital areas (e.g., anus, perineum)

° Can occur in any sacral nerve distribution, e.g. buttocks, upper things, lower abdomen, hip, etc. (“boxer shorts” area)

• Lesions generally not associated with hairs (vs. folliculitis)

• Ulcers usually tender, nonindurated

• Lesions may be small, “nonspecific” in appearance, mimicking excoriation and other noninfectious conditions

• Lymphadenopathy, when present, usually is bilateral, firm, moderately tender, without fluctuance or cutaneous erythema

• Erosive cervicitis in >50% of women with primary herpes; overt cervicitis uncommon in reactivation

• Urethritis in 30–40% of men with primary herpes, often meatal erythema and/or localized tenderness along penile shaft at sites of intraurethral lesions

• Occasional sacral nerve neurological deficits in primary infection (e.g., urinary retention, lax anal

sphincter)

• Deeply erosive genital, perianal, or perioral lesions are common in AIDS patients

• Signs of meningitis, e.g., nuchal rigidity, photophobia

• Erythema multiforme is an occasional systemic response to recurrent genital herpes

LABORATORY DIAGNOSIS

Diagnostic Principles

• Diagnosis in all suspected cases should be virologically confirmed and HSV type determined
• Identification of HSV in lesion by PCR or culture is definitive; negative result usually does not exclude herpes
• Type-specific HSV antibody testing often is diagnostically useful in patients with atypical or culturenegative lesions or who present without current lesions; seroconversion is diagnostically definitive
• Rule out syphilis, chancroid, and other causes of genital ulcer by epidemiologic assessment and appropriate laboratory tests
• Differential of genital ulcer disease includes traumatic lesions (e.g., excoriation in presence of pruritic
syndromes), folliculitis, fissures caused by vulvovaginal candidiasis, aphthous ulcers, Behçet disease,
ulceration due to erythema multiforme (Stevens Johnson syndrome), and other causes

Virologic TestsCulture• Isolation in cell culture is available in most clinical laboratories in industrialized countries
• Yield highest in initial episodes or from recurrent lesions ≤2 days old.

Nucleic Acid Amplification Tests

• Test of choice when available; more sensitive than culture

• PCR and other NAATs are increasingly available in the United States and other industrialized countries

Other Tests

• Direct fluorescence microscopy for HSV less sensitive and does not differentiate HSV-1 from HSV-2; little clinical utility

• Cytologic identification of multinucleated giant cells (Tzanck test) is pathognomonic for herpes but

is insensitive and does not differentiate HSV-1, HSV-1, or varicella zoster virus

Serology

• Type-specific tests, based on antibody specific to HSV glycoprotein G1 (for HSV-1) or glycoprotein

G2 (for HSV-2)

° HerpeSelect IgG HSV-1 and HSV-2 ELISA or immunoblot (Focus Diagnostics)

° Captia IgG HSV-1 and HSV-2 ELISA (Trinity Biotech)

° BiokitUSA HSV-2 rapid point-of care test (Biokit USA)

° Kalon HSV-1 and HSV-2 ELISA (available in the United Kingdom and other countries)

° Several other assays now available in various countries and more are anticipated

• IgG HSV-2 ELISA (HerpeSelect) performance characteristics

° Optical density ratio >1.1 formally defines positive result

° Values 1.1–3.5 may be false positive and require repeat or confirmatory testing

° Values >3.5 are definitely positive

• Intermediate results have not been systematically studied for tests other than HerpeSelect; repeat or confirm positive results that do not accord with clinical manifestations or risk assessment

• HSV Western blot is serological gold standard; final arbiter of uncertain test results requiring confirmation

• An ELISA inhibition assay (Focus Diagnostics) may be useful for confirmation, but may not be commercially available

• Non-type-specific antibody tests

° May be used for inexpensive initial testing; negative result excludes HSV-1 and HSV-2; positive result requires follow-up type-specific test

° Numerous tests marketed worldwide falsely claim to be type-specific; avoid tests that do not explicitly detect antibody to HSV glycoproteins G1 and G2

• HSV-2 seroconversion

° IgG HSV-2 antibody (e.g., HerpeSelect): ~50% of newly infected patients seropositive at 3– 4 weeks, 70–80% at 6–8 weeks, >90% at 3 months

° Seroconversion is slower for Western blot: ~50% at 6–8 weeks, 80% at 3 months, ≥90% at 1 year

° Seroconversion time not well studied for most other assays

• ~5% of persons with HSV-2 infections and ~15% with HSV-1 do not develop detectable type-specific
antibody and have persistently false-negative results
• Antiviral therapy of initial HSV infection may delay or prevent seroconversion
• IgM antibody testing
° Measurable IgM antibody to HSV often does not precede IgG and IgM can persist in recurrent herpes;
therefore, positive IgM test does not reliably indicate infection
° False-positive results are common
° All IgM tests are non-type-specific
° Therefore, IgM testing is rarely useful in clinical diagnosis of either initial or recurrent infection;
routine IgM testing is not recommended

TREATMENT

Antiviral Therapy Principles

• Oral acyclovir, valacyclovir, or famciclovir are mainstays of treatment

• Valacyclovir and famciclovir are “pro-drugs”, i.e., converted to acyclovir and penciclovir during absorption

• Side effects and allergy are rare

• Treatment substantially speeds clinical resolution of initial herpes; lesser benefit for recurrent outbreaks

• Topical acyclovir or penciclovir has little clinical effect, rarely indicated

• HSV drug resistance is rare

° Primarily occurs in immunodeficient patients after prolonged or repeated drug exposure

° Alternative therapies include foscarnet, cidofovir, and topical trifluridine

Recommended Regimens

Initial (Primary and Nonprimary) Genital Herpes

All cases should be treated, even if apparently mild, to shorten duration of symptoms and prevent accelerated course. Even with prompt clinical response, relapse can occur if treatment is stopped early.

• Valacyclovir 1.0 g PO bid for 7–10 days

• Acyclovir 400 mg PO tid for 7–10 days

• Famciclovir 250 mg PO tid for 7–10 days

• Severe cases requiring parenteral therapy: acyclovir 5–10 mg/kg body weight IV every 8 hours for 5–7 days or until improved, then oral valacyclovir, acyclovir, or famciclovir to complete 10–14 days total

Recurrent Genital Herpes

Suppressive therapy is generally preferable to episodic treatment of individual recurrences. Suppression

reduces symptomatic HSV-2 recurrences by 70–80% and in a randomized controlled trial valacyclovir reduced the frequency of sexual transmission by 48%; owing to aspects of study design, actual prevention efficacy may be higher. Acyclovir has not been studied for prevention of transmission but may have efficacy similar to valacyclovir. Famciclovir is somewhat less effective than valacyclovir in suppressing symptomatic recurrences and subclinical shedding. The option of suppressive therapy should be routinely discussed and offered to all patients with genital HSV-2 to help prevent sexual transmission and reduce the frequency of symptomatic reactivation; it is especially indicated for those with >6 outbreaks per year, clinically severe outbreaks, or significant psychological impact of recurrent herpes.

The efficacy of suppressive therapy has not been studied in genital HSV-1 infection and is less frequently indicated in such patients, owing to typically low frequencies of reactivation. Suppressive treatment may be interrupted periodically (e.g., at 1–2 year intervals) to reassess frequency and severity of outbreaks. Some experts recommend that suppressive therapy be deferred for several months after initial diagnosis of genital herpes in order to assess the frequency and severity of recurrent outbreaks unaffected by antiviral treatment and reduce the possibility of delayed seroconversion.

However, delayed treatment may be impractical in patients with new or susceptible sex partners, or for patients with severe psychological impact of newly acquired infection. Episodic therapy is preferred by some patients and speeds healing of recurrent outbreaks by 1–2 days if started within 1 day of onset, and patients with prodrome may abort mucocutaneous outbreaks by prompt treatment. Effective episodic therapy requires prior prescription so that patients have drug available for immediate self-treatment.

Suppressive Treatment

• Valacyclovir 500 mg PO once daily; or 1.0 g PO once daily if ≥10 symptomatic outbreaks per year

° It is plausible, but unproved, that 1.0 g daily may be more effective than 500 mg daily in preventing transmission, regardless of recurrence frequency

• Acyclovir 400 mg PO bid

• Famciclovir 250 mg PO bid

Episodic Treatment

• Valacyclovir 500 mg PO bid for 3 days

• Valacyclovir 1.0 g PO once daily for 5 days

• Acyclovir 800 mg PO tid for 2 days

• Acyclovir 800 mg PO bid for 5 days

• Acyclovir 400 mg PO tid for 5 days

• Famciclovir 1.0 g PO, 2 doses 12 hours apart

• Famciclovir 500 mg PO once, then 250 mg PO bid for 2 days

• Famciclovir 125 mg PO bid for 5 days

Supportive Therapy

• Keep lesions clean and dry by washing 2–3 times daily and wearing loosely fitting cotton underwear

• Topical anesthetic ointment may help control pain, especially in initial genital herpes

Management of Sex Partners

• Evaluate partners not known to have genital herpes

° Type-specific serological test to diagnose subclinical infection and determine susceptibility to infection

° Examine partners promptly (within 1–2 days) if symptoms of herpes appear

Counseling

Advise patient and partner(s) about:

• Available prevention strategies (see Prevention)

• Likelihood of recurrences, frequency of subclinical shedding, and potential for transmission, including differences between HSV-1 and HSV-2

• Elevated risk and frequency of recurrent outbreaks, subclinical viral shedding, and transmission in

first 6 months after initial infection

• Routine disclosure of genital HSV-2 to prospective new sex partners

• Methods to minimize impact of genital herpes on current and new sexual relationships

• Importance of not allowing herpes to substantially affect current or future committed sexual relationships

° Likelihood of mild or subclinical infection in partner if transmission occurs despite attempts to prevent it

° Treatment available in event of significant symptoms

° Main fear of genital herpes is transmission to new partners, generally not a concern in committed relationships

• Elevated risk of HIV infection if sexually exposed

• Risks and prevention of neonatal herpes

• During initial infection, avoidance of autoinoculation and resultant herpetic keratitis or whitlow

° Minimize manual contact with lesions

° Frequent hand washing or alcohol gel

° Autoinoculation is rare in recurrent or long-established HSV infection

• Rarity of HSV transmission in households, by fomites, or from contaminated surfaces; household members (other than sex partners) are not at risk .

PREVENTION

Genital Herpes

• Transmission risk is low, perhaps zero, to partners infected with the same HSV type; partners can be serologically tested to assess susceptibility

• Disclosure of genital herpes to uninfected partners is associated with reduced transmission risk

• Condoms for vaginal or anal sex

° Reduces HSV-2 transmission risk by ≥90% for individual episodes of vaginal intercourse

° Long-term efficacy (use effectiveness) to prevent HSV-2 transmission probably 50–70%

• Suppressive therapy

° Valacyclovir reduces HSV-2 transmission risk by ≥50%

° Acyclovir probably has similar efficacy

° Famciclovir is less effective in suppressing viral shedding and may be less effective in preventing

transmission

• Avoid sex during symptomatic reactivations, from prodrome until healed

• Transmission probably is uncommon when all three strategies (condoms, suppressive therapy, avoiding sex during outbreaks) are used

Neonatal Herpes

• Highest risk is from maternal initial genital infection in third trimester; accounts for ~50% of neonatal herpes

• Serological testing of pregnant women and, if seronegative, their sex partners may help prevent neonatal herpes by identifying discordant couples and counseling them to avoid intercourse or orogenital exposure (depending on HSV type) in third trimester

• Cesarean section for women with clinically apparent herpes lesions at term

• HSV PCR with rapid results (<4 hours) is useful during labor; consider cesarean delivery for suspected initial infection, i.e., patient seronegative to the HSV type identified by PCR

• In recurrent genital herpes, prophylactic acyclovir during last month of pregnancy prevents otherwise unnecessary cesarean deliveries by reducing frequency of symptomatic reactivation; efficacy for preventing perinatal transmission is unknown.

8–1. Primary genital herpes. a. Multiple,

bilateral ulcers of vulva, anus, perineum, and

buttocks. b. Ulcerative cervicitis.

CASE 1

Patient Profile Age 22, single secretary

History Genital and perianal pain, vaginal discharge, fever, and headache for 7 days; boyfriend has recurrent genital herpes, but they carefully avoided sex during symptomatic episodes

Examination Multiple bilateral tender ulcers of labia and medial aspects of buttocks; ulcers and purulent exudate of cervix; tender inguinal lymphadenopathy bilaterally; temperature 38.1°C orally

Differential Diagnosis Genital herpes, contact dermatitis; syphilis and chancroid unlikely

Laboratory HSV-2 isolated from lesions and cervix; syphilis serology, HIV serology, screening NAATs for Chlamydia trachomatis and Neisseria gonorrhoeae (all negative)

Diagnosis Primary genital herpes

Treatment Valacyclovir 1.0 g PO bid for 10 days

Comment Primary infection (i.e., likely seronegative for HSV-1) is suggested by extensive lesions, inguinal lymphadenopathy, cervicitis, and systemic manifestations. The patient reported substantial pain relief after 3 days and her lesions were completely healed after 2 weeks. She was counseled about likelihood of both symptomatic recurrences and subclinical shedding, with risk of transmission to future sex partners (but not to her current boyfriend). Her partner was examined and counseled; he was unaware about subclinical viral shedding and transmission risk between symptomatic reactivations

8–2. Cluster of vesicular lesions typical of recurrent genital herpes of 2–3 days duration.

CASE 2

Patient Profile Age 38, radiology technician

History Penile “blisters” for 2 days, preceded by itching 1 day; two previous similar episodes since initial genital herpes, diagnosed clinically 8 months previously without laboratory confirmation

Examination Cluster of vesicular lesions of penis; no lymphadenopathy

Diagnosis Recurrent genital herpes

Laboratory HSV-2 isolated from lesions

Treatment Valacyclovir 500 mg PO daily as suppressive therapy

Comment Although clinical diagnosis per se did not require laboratory confirmation, viral culture or PCR was indicated to determine virus type. Pain and pruritus resolved over 3 days; the lesions became pustular, then crusted, and healed over 10 days. The patient was counseled about options of episodic or suppressive antiviral therapy, chose the latter, and was symptom-free for the next 6 months.

8–3. Genital herpes: subclinical ulcerative lesion of labia minor, with mild surrounding edema.

CASE 3

Patient Profile Age 28, flight attendant

History Asymptomatic; sought health care after a partner informed her that he had gonorrhea

Examination Nontender ulcer of labia minor, with slight surrounding edema and faint erythema;

otherwise normal

Differential Diagnosis Herpes, syphilis, chancroid, traumatic lesion

Laboratory HSV-2 identified in lesion by PCR; darkfield microscopy negative for Treponema pallidum; type-specific serology positive for antibody to HSV-2; syphilis and HIV serologies negative; cervical NAAT positive for N. gonorrhoeae and C. trachomatis

Diagnosis Subclinical recurrent genital herpes; uncomplicated gonorrrhea and chlamydial infection

Treatment Patient elected suppressive therapy with valacyclovir 500 mg PO daily, primarily to prevent transmission to sex partners; ceftriaxone 250 mg IM (single dose), azithromycin 1.0 g PO (single dose)

Comment This case illustrates unrecognized but not truly asymptomatic recurrent genital herpes, which was diagnosed serendipitously when she presented for care because of exposure to gonorrhea. Although the patient initially denied symptoms suggestive of herpes, after palpating the lesion she recalled previous intermittent awareness of a painless swelling in the same spot. Presence of HSV-2 antibody was consistent with chronic infection.

8–4. Primary genital and oral herpes of 1 week duration: a. Pustular and crusted lesions of penis, with penile edema. b. Oral ulcers. HSV-2 was isolated from both genital and oral lesions.

The patient also complained of severe sore throat and fever. When oral HSV-2 infection is seen, it usually accompanies primary genital herpes. Oral HSV-2 rarely causes symptomatic

recurrences and asymptomatic oral viral shedding is infrequent.

8–5. Primary genital herpes with multiple ulcers of introitus and labia minor. Initial herpes lesions tend to be most prominent at sites of maximum friction during sex.

Primary genital herpes: a. Ulcerative lesions with penile edema; penile venereal edema can accompany urethritis as well as herpes. b. Urethritis with meatal ulceration in the same patient

8–6. Primary genital herpes: a. Ulcerative lesions with penile edema; penile venereal edema can accompany urethritis as well as herpes. b. Urethritis with meatal ulceration in the same patient; urethritis occurs in about one-third of men with primary genital herpes, often with meatal erythema and severe dysuria, sometimes the only manifestation of herpes

8–7. Primary genital herpes with multiple ulcers of foreskin and glans penis.

8–8. Primary anal herpes in a gay man. The patient also had fever and tenesmus, and
anoscopy showed ulcerative proctitis. HSV-2 was isolated

Early (1–2 days) vesicular lesions of initial, nonprimary genital herpes due to HSV-2 in a patient who was seropositive for HSV-1

8–9. Early (1–2 days) vesicular lesions of initial, nonprimary genital herpes due to

HSV-2 in a patient who was seropositive for HSV-1. Clear fluid-filled vesicles with

erythema have been described as “a dew drop on a rose petal,” pathognomonic

for herpes, including chickenpox and shingles. The patient also has penile warts.

8–10. “Nonspecific” superficial ulcerative lesion due to subclinical recurrent herpes.

The patient was asymptomatic until found to be HSV-2-

seropositive and counseled to be alert for previously unrecognized lesions.

8–11. “Nonspecific” labial ulcer resembling an excoriation in recurrent genital
herpes. Many recurrent herpes lesions lack the vesiculopustular characteristics
of classic herpes, perhaps especially when observed ≥2 days after onset or if
lesion is scratched or manipulated.

8–12. Initial genital herpes with a single large penile ulcer mimicking chancroid.

8–13. Large labial ulcers in a woman with initial genital herpes, mimicking chancroid. The
labium was edematous and had become bifurcated, so that the two ulcers were in apposition to
one another. Autoinoculation across apposed surfaces (“kissing lesions”) is considered a classic
sign of chancroid but can also occur in initial genital herpes.

8–14. Initial, nonprimary genital herpes, with a single labial ulcer.
The violaceous nodule anterior to the ulcer is a hemangioma.

8–15. Irregular, nonspecific-appearing penile ulcer in a man with recurrent genital herpes.

8–16. Initial genital herpes in a woman whose only symptom was dysuria, mimicking a urinary tract
infection. Edema surrounds the meatus and the urethra mucosa is ulcerated.