In the name of ALLAH, the Beneficent the Merciful

CHANCEROID

LYMPHOGRANULOMA VENEREUM

GRANULOMA INGUINALE

MUHAMMAD KHAWAR NAZIR

 TODAYS DISCUSSION

• EPIDEMIOLOGY
• ETIOLOGY AND PATHOGENESIS
• CLINICAL FINDINGS
• LABORTARY TESTS
• HISTOLOGY
• DIFFERENTIAL DIAGNOSIS
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WORKING ON THE SKIN
 CHANCEROID
At a Glance:

STD Acute ulcerative Disease

Often associated with inguinal adenitis or bubo

Haemophilus ducreyi

Developing countries (Africa, the Caribbean, and Southwest Asia)

Painful soft ulcers with ragged undermined margins develop 1 to 2

weeks after inoculation.

Azithromycin and ceftriaxone are recommended as a single-dose

treatment.
 EPIDEMIOLOGY
• Developing countries, especially in Africa and Asia

• common in all 18 countries in which adult HIV prevalence

• Epidemic in California in 1981, number of cases increased,

peaking in 1987 at 5035 cases. In 1996, only 386 cases of
chancroid were reported

• Interpretation of chancroid surveillance data is

difficult, because confirmatory culture media or DNA
amplification methods are not commercially available

• True incidence is probably vastly greater than reported

• act.
 EPIDEMIOLOGY
• Prevalence of chancroid is higher in lower socioeconomic
groups

• Recent epidemics in the industrialized countries have

usually been associated with commercial sex work, use of
crack cocaine, syphilis, and an increased risk of HIV
infection

• Lower-class prostitutes appear to be a reservoir

• Men have a markedly higher incidence

• Transmission rate from females to males is not known, but a

transmission rate from males to females of 70 percent
per sex
PAGES FROM HISTORY
 Etiology and Pathogenesis
• Historical Aspects :
• Chancroid, or soft chancre (ulcus molle), was first distinguished from syphilis
by Basserau in France in 1842.

• In 1889, the causative bacillus was discovered and described by Ducrey,

a bacteriologist at the University of Naple

• still unclear who was the first to culture H. ducreyi

• H. ducreyi is a Gram-negative, facultative anaerobic coccobacillus that requires

hemin (X factor) for growth
• small, nonmotile, and non–spore-forming

• exact taxonomy is still controversial

 Biochemistry
• Nitrate reduction is a characteristic of the genus

• Oxidase positive and catalase negative and have a

broad range of phosphatase activity

• Alkaline phosphatase reaction is used in the

identification of the organism

• Differentiation from other hemin-requiring strains of

Haemophilus is made by the organism's lack of
requirement for nicotinamide adenine dinucleotide (V
factor) and its failure to produce hydrogen sulfide,
catalase, or indole.
 Growth Requirements
• Fastidious bacillus

• To get optimal rates of positive culture results, Nsanze et al

recommend the use of 2 media simultaneously

• 1) Gonococcal agar supplemented with bovine hemoglobin

• 2) Mueller-Hinton agar supplemented with chocolate horse

blood

• each with 5 percent fetal calf serum and vancomycin

• Growth is best at 30ºC to 33ºC (86ºF to 91.4ºF) in a water-

saturated atmosphere
 Genetics and Virulence
• The H. ducreyi genome is being cloned

• shares a significant gene pool with members of the

Pasteurellaceae and the Enterobacteriae families

• core plasmid conferring ampicillin resistance in H. ducreyi is

found in other species of Haemophilus and Neisseria

• Production of -lactamase is mediated by plasmids (5000 and 5700

kd) identical to the two types of Neisseria gonorrhoeae
-lactamase plasmid

• Isogenic mutants of H. ducreyi now can be constructed, and the

virulence properties of specific mutants can be determined

• An isogenic hemoglobin receptor–deficient mutant of H. ducreyi was

reported that showed attenuated infection in a human model
 Genetics and Virulence

• Three major factors seem to be important in

the pathogenesis of H. ducreyi infection

1) Adherence to the epithelial surface,

2) Rate of production of exotoxins (e.g.,
cytolethal distending toxin),
3) Resistance of the host defense mechanism

• Details about pathogenesis are still unclear

 Clinical Findings
• Incubation period is between 3 and 7 days,
rarely more than 10 days

• No prodromal symptoms

• Chancre begins as a soft papule surrounded by

erythema

• After 24 to 48 hours it becomes pustular,

eroded, and ulcerated
Sharply circumscribed ulcer
 Clinical Findings

• Vesicles are
not seen
• edges of the
ulcers are
often ragged
and
undermined
 Enlarging cjanceroid with grey exudate, which has
destroyed the frenulum ( Kissing Ulcer )

• ulcer is usually covered by

a necrotic yellowish gray
exudate
• ground is composed of
granulation tissue that
bleeds readily on
manipulation
• In contrast to those of
syphilis, chancroid ulcers
are usually tender, not
indurated (soft chancre),
and painful
• diameter varies from 1 mm
to 2 cm
 Clinical Findings
• Half of males have a single ulcer, and most
lesions are found on the external or internal
surface of the prepuce, on the frenulum, and on
the glans

• The meatus and shaft of the penis and the anus

are involved less frequently

• Edema of the prepuce is often seen. Rarely, if

the chancre is localized in the urethra

• H. ducreyi causes purulent urethritis

Sharply circumscribed ulcer on glans
 Clinical Findings

• In Females the lesions are mostly localized on the

vulva especially on the fourchette, the labia
minora, and the vestibule. Vaginal, cervical, and
perianal ulcers have also been described

• Extragenital lesions of chancroid have been

reported on the breasts, fingers, thighs, and inside
of the mouth

• Trauma and abrasion may be important for such

extragenital manifestations
Vulvar Chanceroid with undermined edges
 Clinical Findings
• Painful inguinal adenitis (bubo) occurs in up to 50 percent of
patients within a few days to 2 weeks (average, 1 week) after
onset of the primary lesion

• The adenitis is unilateral in most patients, and erythema of the

overlying skin is typical

• Buboes can become fluctuant and may rupture spontaneously

• pus of a bubo is usually thick and creamy

• Buboes are less common in female patients

• systemic infection by H. ducreyi has never been observed

Small, soft ulcer on the internal surface of the prepuce with
painful, fluctuant inguinal adenitis (bubo).
 Clinical Variants of Chancroid
• Giant chancroid
Single lesion extends peripherally and shows extensive ulceration

• Large serpiginous ulcer

Lesions become confluent, spreading by extension and autoinoculation. The groin or
thigh may be involved (ulcus molle serpiginosum)

• Phagedenic chancroid
Variant caused by superinfection with fusospirochetes. Rapid and profound
destruction of tissue can occur (ulcus molle gangrenosum)

• Transient chancroid
Small ulcer resolves spontaneously in a few days, may be followed 2–3 wk later by
acute regional lymphadenitis (French: chancre mou volant)

•  Follicular chancroid
Multiple small ulcers occur in a follicular distribution

• Papular chancroid
Granulomatous ulcerated papule may resemble that of donovanosis or condylomata
lata (ulcus molle elevatum).
 Laboratory Tests
• Bacterial culture of H. ducreyi currently remains the primary tool for the diagnosis of
chancroid in the clinical setting

• However, the advent of more sensitive DNA amplification techniques has

demonstrated that the sensitivity of H. ducreyi culture is only 75 percent at best.

• The bacillus will survive only 2 to 4 hours on a swab unless refrigerated. Swabbed
material from the purulent ulcer base should be inoculated directly onto an appropriate
culture medium, because no satisfactory transport system is available

• simultaneous use of two primary isolation media from a nutritionally rich agar base
supplemented with hemoglobin and serum is recommended for high culture sensitivity

• Small, non-mucoid, yellow-gray, translucent colonies appear in 2 to 4 days after

inoculation

• The identification of H. ducreyi is performed following the recommendations of

Lubwama: demonstration of hemin requirement, oxidase and catalase test, -lactamase
test, and hydrogen sulfide and indole activity

• Testing of antibiotic susceptibility is recommended, because clinically significant

antimicrobial resistance of H. ducreyi has become common
 Laboratory Tests
• Direct examination of clinical material by
Gram or Giemsa stain may be helpful, but
reported sensitivity and specificity values are
low—10 percent to 63 percent and 51 percent
to 99 percent, respectively

• The bacilli are usually found in small clusters

or parallel chains of two or three organisms
streaming along strands of mucus. This
pattern has been described as a "school of
fish" or "railroad track"
Smear from soft ulcer showing a "school of fish"
pattern (Giemsa stain).
 Laboratory Tests

• This arrangement, said to be characteristic of H.

ducreyi, is nevertheless not pathognomonic,
because most genital ulcers have a polymicrobial
flora

• Cotton or calcium-alginate swabs are

recommended for specimen collection. Some
authors do not recommend direct microscopy in
the routine diagnosis of chancroid
 Laboratory Tests

Serologic Tests

Many attempts have been made to develop serologic

tests for chancroid

Due to limited sensitivity in the detection of circulating

antibodies to H. ducreyi, serologic testing currently has
imited uslefulness in the routine diagnosis of chancroid
infection

But may be useful in population-based epidemiologic

research as a method of screening for past infection
 Laboratory Tests

Polymerase chain reaction (PCR)

• PCR procedures using different primers have shown greater sensitivity than
bacterial culture

• A multiplex PCR assay has been developed (Roche Molecular Systems,

Alameda, CA) for the simultaneous amplification of DNA targets from H.
ducreyi, Treponema pallidum, and herpes simplex types 1 and 2, which seems
to be a particularly attractive diagnostic tool in the investigation of genital
ulcers in patients

• Multiplex PCR has a resolved sensitivity and specificity for H. ducreyi of 98.4
percent and 99.6 percent, respectively.

• None of these PCR-based methods is commercially available yet, but their use
for routine diagnostic purposes would be clearly advantageous.
 Syndromic Management

• In resource-poor settings in which

diagnostic facilities are not readily available

• World Health Organization advocates the

use of a syndromic management approach
for patients with genital ulcer disease
 Histology
• Characteristic histologic features with three vertically arranged
zones have been described in chancroid

1) superficial necrotic zone

2) a zone of new blood vessel formation beneath

3) a deep zone consisting of dense lymphocytic and plasma cell

infiltrate

• Tissue biopsy is not a recommended diagnostic method, but

histologic examination may be useful to exclude malignancy in non-
healing or atypical ulcers

• Staining with H. ducreyi-specific monoclonal antibodies

demonstrates the organisms chiefly within the granulocytic infiltrate
and fibrin of the ulcer.
Zone of Neutrophil, fibrin& necrotic tissue beneath the
ulcer, underlying zone of vascular proliferation
 Differential Diagnosis

• 3 classic causative agents for genital ulceration are

H. ducreyi,
T. pallidum,
Herpes simplex

• The clinical appearance of the diseases caused by these three agents can be
extremely variable in both men and women

• Therefore clinical diagnosis of genital ulcer disease can be made with reasonable
certainty for only a minority of patients

• The cause of genital ulcers also differs considerably by geographic region

• In industrialized countries isolated painful chancres are most likely due to herpes
simplex virus

• In a high percentage of genital ulcers no pathogen can be isolated, but co-infections

of H. ducreyi with T. pallidum (ulcus mixtum) or herpes simplex virus are not
uncommon
 Differential Diagnosis

Disease/Condition Etiologic Agent

Most Likely

Genital herpes Herpes simplex virus types 1 and 2

Syphilis Treponema pallidum 

 
Lymphogranuloma venereum Chlamydia trachomatis serovars L1–L3 
 Differential Diagnosis

• Consider 

• Other bacterial sexually transmitted infection:

granuloma inguinale (donovanosis)Calymmatobacterium granulomatis  

• Other bacterial infections

Streptococcus sp., fusospirillary infections, Mycobacterium tuberculosis,

Corynebacterium diphtheriae (very rare)  

• Viral infections    

Acute HIV infectionHIV   

Ulcus vulvae acutum Epstein-Barr virus    
Cytomegalovirus   
Genital herpes zoster Varicella-zoster virus 
 Differential Diagnosis
• Consider 
• Parasitic infections    

AmebiasisEntamoeba histolytica    
LeishmaniasisLeishmania sp.     
ScabiesSarcoptes scabiei  

• Inflammatory diseases
(e.g., Behçet disease, aphthosis, Crohn disease, pyoderma gangrenosum)  

• Drug adverse effects    

Fixed drug eruptionFor example, trimethoprim-sulfamethoxazole   Toxic effectsFor

example, foscarnet 

• Traumatic and self-induced genital ulcers and neoplasms 

 Differential Diagnosis

• Always Rule Out 

• Genital herpesHerpes
simplex virus types 1 and 2 

• Syphilis T. pallidum  

• HIV infection HIV

BAADSHAAHI MOSQUE
THANK YOU