1. 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

2. 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.

3. 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

4. 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.

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

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

7. 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.

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

9. 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% %
LIFETIME LATENCY TERTIARY

10. PRIMARY SYPHILIS

11. PRIMARY SYPHILIS

12. 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)

13. SECONDARY SYPHILIS

14. SECONDARY SYPHILIS

15. SECONDARY SYPHILIS

16. SECONDARY SYPHILIS
Adenopathy Patchy Alopecia

17. SECONDARY SYPHILIS
Condyloma lata

18. 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”

19. 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

20. 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.)

22. 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

23. 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

24. Non-specific Serologic Tests (RPR, VDRL, ART, etc)
Quantification:
1:1 1:2 1:4 1:8 1:16 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

25. 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

26. 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 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.

27. 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

28. 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

29. CHANCROID
Genital Ulcer with Inguinal Buboes in 50%

30. 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

31. 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

32. 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

33. 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)

34. 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

35. 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)

36. 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

37. HERPES SIMPLEX

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

39. RECURRENT HERPES SIMPLEX

40. 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

41. 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

42. 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

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

44. 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

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

46. 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

47. 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

48. 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

49. 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

50. 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