This document summarizes several genital ulcer diseases other than syphilis. It describes the causative organisms, epidemiology, pathogenesis, clinical features, diagnosis and management of chancroid, donovanosis, lymphogranuloma venereum (LGV), herpes genitalis and provides comparisons of these diseases. It notes that HIV infection can result in larger, more persistent ulcers and increased risk of multiple buboes in chancroid patients.

1. Genital ulcer diseases other
than syphilis
Presenter : Dr. Sasmita Mishra
Moderator : Dr. Biswanath Behera

2. Chancroid
• Causative organism-Haemophilus ducreyi, fastidious gram negative coccobacillus
• Incidence- High risk
a) Lower socioeconomic status
b) Commercial sex workers
c) Uncircumcised men
Male to female ratio- 3:1-53:1
Prevalance- 0.0%-0.15%

3. Pathogenesis
Inoculation through minor trauma/ abrasion
IL-8 IL-6
Stimulate PMNs and stimulates CD4- Tcells
macrophages
Pustules ulceration by IL-2 activation
• Cytolethal Distending Toxin (CDT)- Virulence factor for ulceration

4. Clinical features
• Incubation period- 1-14 days (avg 7 days)
• Evolution of lesion-
Erythematous papule pustule ulcer
2-3 days 2-3 weeks (soft chancre)
• Characteristics of ulcer-
Single/Multiple, painful, non-indurated
undermined ragged edge
necrotic yellowish-gray exudate
Base with granulation tissue

5. Contd……….
• Onset- 1 -2 weeks , seen in- 50-60% cases, usually unilateral
• Lymph nodes –Painful, enlarged, tender, matted- Bubo
• If untreated, unilocular abscess sinus
• No systemic infection
• Asymptomatic carrier rare
• Females may have painless ulcer

6. Sites
• Genital:
Male- prepuce,frenulum, coronal sulcus
Female- Fourchette, vestibule, labia, clitoris, vagina
• Extragenital:
Breast, fingers, thigh, oral cavity, lip
Rarely involved due to autoinoculation
• Perianal ulcers- usually seen in men who have sex with men (MSM)

7. Clinical variants
• Giant chancroid.
• Large serpiginous ulcer (ulcus molle serpiginosum)
• Phagedenic chancroid (ulcus molle gangreosum)
• Transient chancroid (chancre mou volant)
• Follicular variant
• Papular (ulcus molle elevatum)
• Dwarf
• Pseudogranuloma inguinale

8. Complications
• Scar formation
• Fibrosis
• Lymphedema
• Phimosis
• Paraphimosis
• Urethral fistula

9. Diagnosis
• Usually clinically
• Gram’/Wright’s stain- School of fish appearance.
• Ito- Reenstierna test (intradermal test) - Obsolate now
• Definitive diagnosis- Culture ( Chocolate agar)
PCR (most sensitive)

10. Histopathology
• Shows 3 distinctive zones
a) Top zone- narrow, consisting of neutrophils,fibrin
erythrocytes, necrotic tissue
b) Middle zone- wide, newly formed blood vessels
with marked endothelial cell proliferation
c) Lower zone- dense infiltrate of plasma cells &
lymphoid cells

11. Differentials
• Genital herpes
• Syphilis
• LGV
• Behcet’s disease
• Apthousis
• Fixed drug eruption
• Traumatic lesions with secondary bacterial infection

12. Criteria for probable diagnosis according to CDC
• 1 or more painful genital ulcers
• Dark field examination of exudate- negative for T. Pallidum
• Non reactive serological tests - at least 7 days after onset of ulcers
• Typical clinical finding with regional lymphadenopathy
• Negative test for HSV (HSV PCR / Culture)

13. Management ( According to CDC)
• Azithromycin 1g orally as single dose, or
• Ceftriaxone 250mg IM as single dose, or
• Ciprofloxacin 500mg BD for 3 days, or
• Erythromycin 500mg TDS for 7 days

14. Drug resistance
• Plasmid mediated
• Integrated Conjugative resistance Element (ICE)- also responsible
• Resistance develop to ampicillin, chloramphenicol, tetracycline

15. Management of bubo
• Adequate antibiotic coverage with aspiration
• If size < 5 cm- heals with resolution of genital ulcer
• If size > 5 cm- not correspond to resolution of ulcer
• Advantage of Incision and drainage- Effective, safe method, avoids frequent
needle re-aspiration, early healing of lesion

16. Post- treatment follow up
• At 3rd day and 7th day of initiation of treatment
Symptomatic Significant
improvement re-epitheliazation
• If no response to treatment- coinfection with T. Pallidum/HSV suspected
• Sexual partner treated : < 10 days
• HIV and VDRL – to repeat after 3 months

17. Donovanosis
• Caused by- Klebsiella granulomatis, Gram negative intracellular bacteria
• Epidemiology- Risk factors includes
a) Low socioeconomic status
b) Overcrowding
c) Poor hygiene
• M:F- 4:1
• Prevalance- 6.3%
• Age group -20-40 yrs

18. Contd………
• Route of transmission- Trauma/abrasion during sexual contact
Autoinoculation
• Sites- Most common- Genitals ( Coronal sulcus, prepuce, glans penis in male,
labia minora, fourchette in female)
Others- Inguinal region, anal area, oral cavity
urethra and rectum spared

19. Clinical features
• Incubation period- 40-50 days
• Evolution- Single/Multiple firm papules
Granulomatous ulcer
• Ulcer characteristics-
Slowly progressive,painless
Beefy red in colour
Bleeds on touch
• Subcutaneous extension - Pseudobubo

20. Morphological variants
Classical granulomatous type-
• Most common presentation
• Edge thin and undermined
• Granulation tissue overflow from the edge
• Skin around ulcer slightly edematous and infiltrated
• Non capsulated organism found

21. Contd……..
Hypertrophic type-
• Ulcer edge thickened and raised above surrounding skin
• Consists of pale red, course ,warty granulation tissue ( Buckled appearance)
• No exudates
• Capsulated organism found

22. Contd……..
Sclerotic/Cicatrical :
• Early and extensive formation of fibrous tissue
• Results in deformities of genitalia
Phagedenic (Destructive/Necrotic type) :
• Due to superadded anaerobic infection Ulcer becomes painful

23. Complications
• Pseudoelephantiasis
• Epidermoid carcinoma
• Psoas/Perinephric abscess
• Spinal cord compression
• For oral lesions, leads to microstomia and nasal regurgitation

24. Differentials
• Primary syphilis
• Lymphogranuloma venerum
• Chancroid
• Chronic herpes simplex

25. Diagnosis
• Direct microscopy- Donovan bodies- Mononuclear cells with organism
( safety pin appearance)
Gold standard
• Biopsy- indicated in chronic ulcer
• Serological tests- Complement Fixation Test
• Culture
• Colorimetric detection system

26. Management (According to CDC)
• Azithromycin 1g orally once weekly, or
500mg daily for at least 3 weeks
and all lesions completely healed
Alternatively,
• Doxycycline 100mg BD for at least 3 weeks,or
• Ciprofloxacin 750mg BD for at least 3 weeks,or
• Erythromycin 500mg QID for at least 3 weeks, or
• Cotrimoxazole ( 160mg/800mg) BD for at least 3 weeks

27. Contd……..
• Sexual partner treated : < 60 days
• For pregnancy/Lactation- Macrolide regimen preferred
• For HIV infection treated as non- HIV patients
• if no improvement add Aminoglycoside ( Gentamicin 1mg/kg IV in
every 8 hours)

28. Post treatment follow up
• Monthly for first 3 months
• Subsequent follow ups- according to level of healing and relapses

29. Lymphogranuloma venerum
• Caused by- Chlamydia trachomatis (mostly serovar L2), prevalence-0.27%-11.5%
• Pathogenesis & pathology :
Thrombolymphangitis and perilymphangitis
Proliferation of endothelial cells
Draining lymph nodes enlarge and form necrosis

30. Contd………
Stellate abscess
Inflammation progress
Periadenitis with matting of lymph nodes
Loculated abscess
Rupture

31. Contd…….
• Chronic inflammation
Healing by fibrosis
Compromise blood supply Obstruction of lymph vessels
Ulceration Chronic edema
Induration/enlargement of
affected parts

32. Clinical features
• Incubation period- 3-12 days
• Divided into 3 stages :
a) Primary stage
b) Secondary stage (Inguinal syndrome)
c) Tertiary stage

33. Primary stage
• Four morphological forms:
a) Papules c) Vesicular lesions
b) Ulcer/Erosions d) Non- specific urethritis
• Most common form- Non indurated ulcer
• Usually unnoticed
• Tender, chord like swelling- Bubonulus

34. Sites
• In males :
Coronal sulcus > frenulum > prepuce > shaft of penis > urethra > scrotum
• In females :
Posterior vaginal wall > fourchette > posterior lip of cervix > vulva
• Very rare sites include :
Tonsils, nasolabial folds, sub- mammary region, umbilical area

35. Inguinal syndrome ( bubo)
• IP : 10 days- 6 months(avg- 10-30days)
• Unilateral inflammatory swelling
of inguinal lymphnodes
• Groove sign of Greenbalt (20% cases)

36. Genito-anorectal syndrome
• Mimics IBD - Proctitis and proctocolitis
• Symptoms- rectal bleeding, ‘pencil’ stool, constipation, haematochezia
• Early change – perianal edema multiple fissures
• Late change – mucosal ulceration
rugosities
stricture

37. Complications
• Lymphatic obstruction- Ram-horn penis, saxophone penis in male
Esthiomene in female
• Rectal strictures with/without proctitis and colitis
• Perianal abscess (perianal condyloma)
• Perianal fistula
• Rectovaginal fistula
• Urethral fistula

38. Bubo in LGV and Chancroid
Bubo in LGV Bubo in Chancroid
Genital ulcer not present Genital ulcer present
Bubo less painful Painful
Matting of lymph nodes present Absent
Multilocular suppurative swelling Unilocular suppurative swelling
Rupture to form multiple sinuses Rupture to form ulcer
Heals with scarring Heals with minimal scarring

39. Differentials
• Primary stage : Ulcerogenital diseases, trauma, balanitis, FDE
• Secondary stage : Incarcerated inguinal hernia, reactive inguinal lymphadenitis,
Bubonic plague,Lymphoma, IBD, cat-scratch disease
• Tertiary stage : Malignancy, deep fungal infection, hidradenitis suppurativa

40. Diagnosis
• Serological tests-
a) complement fixation test- titer > 1:64
b) Microimmunofluroscence- titer > 1: 256
• Polymerase chain Reaction (PCR)
• Histopathology- multiple stellate abscess
• Frei’s test- obsolete now
• Lymphangiography, CT scan or MRI- extent of lymph node involvement

41. Management (according to CDC)
• Doxycycline 100mg BD for 21 days, or
Erythromycin 500 mg QID for 21 days, or
Azithromycin 1 gm orally once weekly for 3 weeks
• Sexual partner treated : < 60 days with
Azithromycin 1 gm orally single dose, or
Doxycycline 100mg BD for 7 days
• Pregnancy/lactation- Erythromycin
• For HIV- same as non HIV for prolong duration

42. Herpes genitalis
• Caused by- both HSV-1(Pre.-2.2%) & HSV-2 (prevalence-7.9%-14.6%)
• Pathogenesis- Viral protein ICP-47
interacts with transporter activated protein
prevent interaction with HLA- 1 molecules
Downregulate CD8- T cell response to HSV
• Pathology :
Ballooning/Reticular degeneration
Multinucleated giant cells

43. Clinical features
Divided in 2 episodes :
a) Primary episode- true primary
Non primary
b) Recurrent episode
Primary episode :.
• Different stages of evolution
• Vesicles/ pustules/erythematous ulcers
• Resolves within 2-3 weeks
• More prodromal symptoms, lymphadenopathy
• More complications

44. Contd……
Recurrent episode :
• Multiple small, grouped,vesicular lesions
• Large coalescent areas of ulceration
• With polycyclic margin
• Less severe, less prodrome, confined

45. Contd…..
• Risk of acquisition of HSV-1 with prior HSV-2- unusual
HSV-2 with prior HSV-1- common
• Previous HSV-1 infection with frequent recurrence- tested for HIV
• Herpes cervicitis in 60% cases

46. Complications
• Usually after untreated 1st episode
• CNS involvement
• Extragenital involvement
• Disseminated infections
• Secondary infections

47. Diagnosis
• Usually clinically
• Tzanck smear
• Histopathology
• Viral culture
• Serology
• PCR

48. Management ( according to CDC)
Primary episode:
• Acyclovir 400mg TDS for 7-10days, or
200mg orally five times/day for 7-10 days, or
• Valacyclovir 1 gm BD for 7-10 days, or
• Famciclovir 250mg TDS for 7-10 days
* Treatment extended –if no healing > 10 days

49. Contd………
• Recurrent episodes :
a) Suppressive therapy- Acyclovir 400mg BD, or
Valacyclovir 500mg/1 gm OD, or
Famciclovir 250mg BD
b) Episodic therapy- Acyclovir 400mg TDS for 5 days, or
800mg orally BD for 5 days, or
800mg orally TDS for 2 days

50. Contd…….
• Valacyclovir 500mg BD for 3 day, or
1 gm orally OD for 5 days
• Famciclovir 125mg BD for 5 days, or
1 gm BD for 1 day, or
500mg orally OD f/b 250mg BD for 2 days

51. Comparison of selected cases of genital ulcers
Disease Incubation
period
Ulcer
description
Inguinal
involvement
Miscellaneous Diagnosis
Chancroid 3-7days Painful,ragged
border, and
necrotic
exudates
Unilateral,
tender
lymphadenopat
hy in 50%,
progress to
suppurative
buboes
Ulcer can
persists for
weeks if
untreated.
Culture or PCR
of ulcer base
Donovanosis 1-360 days Painless, beefy
red, bleed easily,
and kissing
lesions
Superficial
spread to
inguinal region
can cause
pseudobuboes
Untreated lead
to scarring and
lymphedema
Donovan bodies
on microscopy
Genital HSV 2-7 days Painful,
clustered,
shallow and
erythematous
base
Bilteral ,tender
lymphadenopat
hy
Often
recurrent,ulcer
heals in aweek
PCR or culture
of vesicular fluid

52. Contd…….
Disease Incubation
period
Ulcer
description
Inguinal
involvement
Miscellaneous Diagnosis
LGV 3-30 days Variably painful,
transient
U/L or B/L,
variably painful,
delayed by 1-4
weeks, can
progress to
suppurative
buboes
Usually
solitary,often
subclinical and
heals without
treatment
NAAT, culture,
serology
Primary syphilis 14-28 days Painless,well
demarcated,smo
oth/shiny, and
indurated
border
U/L or B/L,
painless
lymphadenopath
y without
suppuration
Solitary lesions,
often
subclinical,
heals without
treatment
Dark-field
microscopy of
ulcer, serology

53. Effect of HIV on STDs
STDs Effects
Chancroid Large ulcer, longer persistence, multiple inguinal
buboes, frequent occurrence of giant and phagedenic
ulcer
Herpes genitalis Deep progressive ulcers, haemorrhagic and ecthyma
like lesions, hyperkeratotic verrucous
lesions,pseudotumour of tongue
Granuloma inguinale Larger,extensive lesion, pseudobubo may burst
producing ulceration, slow response to treatment
LGV Acute inflammation, bilateral inguinal bubo may burst
into ulceration.

54. Prevention
• Behaviour change
• Avoidance of unprotected sexual intercourse
• Correct use of condoms
• Periodic evaluation
• Health education, counselling
• Community awareness
• Availability of specific diagnostic tests

55. References
• Sharma Vinod K,editor. Sexually Transmitted Diseases and HIV/AIDS, 2nd ed.New
Delhi: Vinod Publishers; 2003
• Holmes king K,Sparling P. Frederick,Stamm Walter E, et.al. Sexually Transmitted
Disease,4th ed.New York: McGrawHill publishers;2008
• Sexually Transmitted Diseases Treatment Guidelines, Centre of Disease Control
and Prevention; 2015

56. THANK YOU