LSUHSC SECTION OF INFECTIOUS DISEASES DELGADO PERSONAL HEALTH CENTER GENITAL ULCER DISEASE STEPHANIE N. TAYLOR, MD LSUHSC SECTION OF INFECTIOUS DISEASES MEDICAL DIRECTOR, DELGADO PERSONAL HEALTH CENTER NEW ORLEANS, LA

DISCLOSURE I have no financial interests or other relationship with manufacturers of commercial products, suppliers of commercial services, or commercial supporters. My presentation will not include any discussion of the unlabeled use of a product or a product under investigational use.

GENITAL ULCER DISEASE STDs Non-STDs Differential Diagnosis: Syphilis, Herpes, Chancroid LGV, Granuloma inguinale, Ectoparasites (infected) Non-STDs Trauma, fixed drug eruption, neoplasia Aphthous ulcers, non-STD infection, Crohn’s Ds. Behçet’s Syndrome – Oral and/or genital ulcers (not alone), cutaneous lesions, uveitis, arthritis, phlebitis Reiter’s Syndrome – arthritis, conjunctivitis, urethritis, circinate balanitis, keratoderma blennorrhagicum

Primary and secondary syphilis — Rates by state: United States and outlying areas, 2008 Note: The total rate of P&S syphilis for the United States and outlying areas (Guam, Puerto Rico and Virgin Islands) was 4.5 per 100,000 population. The Healthy People 2010 target is 0.2 case per 100,000 population.

Primary and secondary syphilis — Age- and sex-specific rates: United States, 2008

Primary and secondary syphilis — Male-to-female rate ratios: United States, 1981–2006

Primary and secondary syphilis — Reported cases Primary and secondary syphilis — Reported cases* by stage and sexual orientation, 2008 *20% of reported male cases with P&S syphilis were missing sex of sex partner information. †MSM denotes men who have sex with men.

Primary and secondary syphilis — Cases by sexual orientation and race/ethnicity, 2008

SYPHILIS STAGING INFECTION PRIMARY CHANCRE SECONDARY LATENCY (3 WEEKS) PRIMARY CHANCRE (1-3 MONTHS) SECONDARY (1-3 MONTHS / 60-90%) LATENCY (2-50 YEARS) 70% 30% LIFETIME LATENCY TERTIARY

PRIMARY SYPHILIS

PRIMARY SYPHILIS

Manifestations of Secondary Syphilis Rash (may be anywhere or look like anything) Mucous patches; condylomata lata Lymphadenopathy ‘Moth eaten’ alopecia Systemic symptoms (fever, headache, fatigue, arthralgia/myalgia)

SECONDARY SYPHILIS

SECONDARY SYPHILIS

SECONDARY SYPHILIS

SECONDARY SYPHILIS Adenopathy Patchy Alopecia

SECONDARY SYPHILIS Condyloma lata

LATENT SYPHILIS Period during which there is no clinical evidence of disease Serological tests are positive Arbitrarily divided into “early latent” (infection occurred within the last year) or “late latent”

TERTIARY SYPHILIS Slowly progressive disease - affects any organ system and produces clinical illness years after initial infection NEUROSYPHILIS - meningitis, general paresis, optic neuritis (  WBCs, + CSF VDRL,  Prot.) CARDIOVASCULAR - aortic aneurysm, aortic regurgitation GUMMATOUS - large indurated lesions of skin, GI tract, mouth

DIAGNOSIS Darkfield examination of material from a moist lesion – 70-80% sensitive Serologic Tests Non-treponemal (Non-specific) – RPR, VDRL, ART Treponemal (Specific) – FTA-ABS, TPHA, IgG Silver stain of biopsy material DNA Methods (PCR, etc.)

Specific Serologic Tests (IgG, MHA-TP, FTA-Abs, etc) Detect antibody to specific treponemal antigens (fewer false positives) May be negative in primary syphilis (70 – 80% sensitive) Remain positive for life

Non-specific Serologic Tests (RPR, VDRL, ART, etc) Detect antibody to cardiolipin, cholesterol and lecithin (false positives are possible) May be negative in primary syphilis (70%– 80% sensitive) but almost always positive in secondary syphilis Reported as reactive, weakly reactive, non-reactive or may be quantified

Non-specific Serologic Tests (RPR, VDRL, ART, etc) Quantification: 1:1 1:2 1:4 1:8 1:16 1:32 1:64 …. 1:512 etc. Titers decrease after successful therapy (re-check at 6 and 12 months) A fourfold decrease (2 dilutions) 6 months after treatment is considered a sign of successful treatment

Non-specific Serologic Tests (RPR, VDRL, ART, etc) Titers should eventually fall to zero (non-reactive) after treatment 10% – 15% of patients remain “serofast” at a low titer - This can result in problems with test interpretation years later

Syphilis: 2006 CDC STD Treatment Guidelines Primary, Secondary, and Early Latent Benzathine penicillin 2.4 MU IM PCN allergic– Doxy. 100 mg po bid for 14 days Late Latent Benzathine penicillin 2.4 MU IM q wk. x 3 injections PCN allergic – Doxy. 100 mg po bid x 4 weeks Neuro-Syphilis – Aqueous crystalline PCN 3-4 MU IV q 4 hrs 10-14 days – PCN Allergic need to be desensitized Special Circumstances Pregnant and PCN allergic – desensitize and treat HIV – Same tx. for stage of syphilis in non-HIV pt.

CHANCROID ETIOLOGY EPIDEMIOLOGY Haemophilus ducreyi Fastidious organism difficult to isolate Requires supplemented chocolate agar and 5% CO2 for growth EPIDEMIOLOGY Seen more commonly in third world countries Only 25 cases reported in the U.S. in 2008, but outbreaks have been seen in the past

CLINICAL MANIFESTATIONS Incubation period 5-7 days A papule develops initially but goes on to erode into a painful, soft, and non-indurated ulcer 50% of patients will develop painful local adenopathy which may suppurate or rupture

CHANCROID Genital Ulcer with Inguinal Buboes in 50%

Chancroid: 2006 CDC STD Treatment Guidelines Azithromycin 1 gm orally single dose Ceftriaxone 250 mg IM single dose Ciprofloxacin 500 mg po bid for 3 days Erythromycin base 500 mg po qid for 7 days

Herpes Simplex Virus - Pathophysiology Mucocutaneous infection; retrograde migration along sensory nerves; latency in dorsal spinal root or trigeminal ganglia; re-activation and recurrent outbreaks. HSV–1: most infections are orolabial 20% of new genital herpes cases HSV-2: almost always genital infection orolabial infection is rare

GENITAL HERPES Most common cause of genital ulcer disease in N.A. Primary Infection 80-90 % due to HSV-2 Typically most severe, systemic symptoms common Mult. painful vesicles, shallow ulcers, heal 2-3 wks Recurrences Less severe lesions Shorter duration Most patients with HSV-2 asymp. or do not recognize symptoms Asymptomatic viral shedding occurs without outbreaks

Genital herpes — Initial visits to physicians’ offices: United States, 1966–2005 Note: The relative standard error for genital herpes estimates range from 20% to 30%. SOURCE: National Disease and Therapeutic Index (IMS Health)

Disease Spectrum in HSV-2 Seropositive Persons 20% - Clinical manifestations are recognized as genital herpes 60% - Clinical manifestations are not recognized as genital herpes 20% - Subclinical

Genital Herpes Initial Presentations for Care 20% - True primary infection 40% - Non-primary first episode of genital HSV 40% - First clinical manifestations of a prior genital HSV infection (recurrence)

Features of Primary HSV-2 Infection 3-week illness Many lesions, frequently bilateral Mucosal involvement is common Pain may be severe Lymphadenopathy is common Systemic symptoms are common

HERPES SIMPLEX

Features of Recurrent Genital Herpes 5 – 10 days Fewer lesions, usually unilateral Mucosal involvement is uncommon Lymphadenopathy is uncommon Systemic symptoms are uncommon

RECURRENT HERPES SIMPLEX

Recurrence of Herpes Outbreaks Mean number of outbreaks in first year after initial genital HSV-2 infection: - men 5.2 outbreaks/year - women 4.0 outbreaks/year Rate declines over time Rates are lower in genital HSV-1 infection ? Precipitating factors

Subclincal Shedding of HSV Seen in > 95% of persons with HSV-2 (much less common in genital HSV-1) More frequent in first year after infection (detected on 5 – 10% of days by culture and 20 – 30% of days by PCR) Less frequent over time (2 –3% of days) Responsible for most transmission

Diagnosis of Genital Herpes Clinical diagnosis has good specificity in classic cases but lacks sensitivity due to atypical and subclinical cases Culture (or DFA) 50 – 70% sensitivity “Type specific” serologic assays with good sensitivity and specificity are now available

Treatment of Genital Herpes Primary and Non-primary Initial Infections Treat most patients

CDC 2006 STD Treatment Guidelines Treatment of First Episode Acyclovir 400 mg TID for 7-10 days Acyclovir 200 mg 5x/day for 7 – 10 days Valacyclovir 1 g BID for 7 – 10 days Famciclovir 250 mg TID for 7 – 10 days

Treatment of Genital Herpes Primary and Non-primary Initial Infections - treat most patients Episodic Recurrences - treatment may have minimal benefit

CDC 2006 STD Treatment Guidelines Treatment of Episodic Recurrences Acyclovir 400 mg TID for 5 days Acyclovir 800 mg BID for 5 days Acyclovir 800 mg TID for 2 days Valacyclovir 500 mg BID for 3 days Valacyclovir 1000 mg q day for 5 days Famciclovir 125 mg BID for 5 days Famciclovir 1000 mg BID for 1 day

Treatment of Genital Herpes Primary and Non-primary Initial Infections - treat most patients Episodic Recurrences - treatment may have minimal benefit Suppressive Therapy - indicated when outbreaks are frequent - should be discussed with all patients

CDC 2006 STD Treatment Guidelines Suppressive Therapy Acyclovir 400 mg BID Valacyclovir 1 g q day Valacyclovir 500 mg q day Famciclovir 250 mg BID Reassess the need for continued therapy

HSV - 2006 STD Treatment Guidelines Initial Episode Acyclovir, famcicloivir, or valacyclovir X 7-10 days Recurrences Acyclovir, famcicloivir, or valacyclovir X 5 days 2006 STD Guidelines – add 1, 2 and 3-day regimens Suppressive Therapy Indicated for patients with 6 outbreaks a year Reduces the frequency and asymptomatic shedding

Approach to the Patient with GUD History and exam - if the presentation is “classic” then treat based on your clinical diagnosis Testing - syphilis serology and darkfield (if available) - culture or serology for herpes (if available) - HIV testing If diagnosis is not clear, treat for primary syphilis