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In the name of ALLAH, the Beneficent the Merciful

Granuloma Inguinale

MUHAMMAD KHAWAR NAZIR


WEEKEND CELEBRATIONS
Granuloma Inguinale
At a Glance
•GI or donovanosis - chronic ulcerative debilitating
disease, mainly affects the genital organs.

•Caused By Gram-negative bacteria Klebsiella


granulomatis

•Affects mostly people of lower socioeconomic status of


tropical and sub-tropical areas

•Diagnosis is made by demonstrating intracellular


Donovan bodies on histology
Epidemiology and Mode of Transmission

• The mode of transmission of granuloma inguinale (GI) is controversial

• It is generally considered sexually transmitted, but fecal contamination and


autoinoculation remain a possibility, especially in the setting of infected
children and adults without sexual activity and primary involvement of
remote extragenital sites

• Transmission rate between sexual partners is low compared with other


sexually transmitted diseases and was found to be not more than 50 percent

• The incidence of GI is also relatively low among both prostitutes and their
conjugal partners. Nevertheless, this disease predominantly affects sexually
active individuals

• Moreover, donovanosis, being an ulcerative disease, increases the risk of HIV


transmission
Epidemiology and Mode of Transmission

• Transvaginal transmission of donovanosis during delivery has


been reported, with an apparent predilection to ear structures of the
newborn.

• Low socioeconomic classes

• No racial predilection

• Both male and female predominance

• Delay in seeking medical attention due to the painless nature


of the ulcers and the possible embarrassment or fear from medical
or surgical intervention

• Late cases can be very debilitating and are much more difficult to
manage.
Epidemiology and Mode of Transmission

• GI is endemic in warm, moderately humid areas like


South Africa, India, Southern China, and Brazil.

• There are new endemic areas of donovanosis, mainly


South and Central America, India, and Papua New
Guinea, but the overall incidence of GI seems to be
decreasing, especially in Papua New Guinea.

• The disease has nearly been eradicated from Australia,


with only five cases reported in 2004, and is rare in North
America and Europe.
Etiology
• Klebsiella granulomatis, previously called
Calymmatobacterium granulomatis.

• The name has been changed after sequencing the phoE and
16S ribosomal RNA genes and demonstrating close homology with
K. pneumoniae and K. rhinoscleromatis.

• Gram-negative, nonmotile, pleomorphic bacterium that stains


well with Giemsa, Wright's, or silver stains but is periodic acid-
Schiff–negative.

• The mature form is encapsulated, while the immature form is not.


The immature non-encapsulated form may assume a closed-
safety-pin appearance due to bipolar chromatin densities.
Etiology

• Difficult to culture and store this organism; however, it may be


cultured using embryonic chick heart or chick embryo amniotic fluid

• Also been cultured in human peripheral blood mononuclear cells after


decontaminating the specimen with amikacin, vancomycin, and
metronidazole, and in HEp-2 cells after adding gentamicin and
cycloheximide

• Facultative organism that resides in the cytoplasm of large mononuclear


cells

• Pathogenic only to humans and the developing chick embryo. It was


isolated from the feces of 2 out of 4 patients with donovanosis, although
it has not been successfully cultured from feces

• It is still unknown if this organism has a natural habitat


Clinical Findings
History and Cutaneous Lesions

• Incubation period extends from 3 days to 3 months but is usually


2 to 3 weeks

• Single or multiple papules or nodules later develop and grow into a


painless ulcer that may extend to the adjacent tissues and moist
folds, forming "kissing lesions."

• Male: penis, scrotum, and glans are the most commonly affected

• Females: and the labia and perineum are most commonly affected
in females. Vaginal and cervical involvement has also been reported
and sometimes mistaken for squamous cell carcinoma

• The anus and colon may be infected, especially in homosexual


males
Clinical Findings

• GI most commonly presents as

Beefy red

Easily bleeding

Foul-smelling ulcers with granulation tissue


Granuloma inguinale on the inner prepuce. Two beefy red erosive
plaques that bleed easily. (Used with permission from Shukrallah
Zeynoun, MD.)
Clinical Findings

• The ulcers may have

Hypertrophic or verrucous borders


resembling condylomata acuminata

It may also present as soft, red nodules


that eventually ulcerate
Granuloma inguinale. Nodular variety evolving into a large,
exuberant ulcer. (Used with permission from A. Eichmann,
MD.)
Ulcerated lesions on penis & pubic area
Clinical Findings

• In long-standing donovanosis

• the lesions may be necrotic, quite


destructive of tissue, and have a copious
gray, foul-smelling exudate
Granuloma inguinale. Large
ulcerovegetative type.
Clinical Findings
• Tissue overlying the regional lymph nodes may
evolve into an abscess or pseudobubo that
later ulcerates

• Lymph nodes per se are rarely involved unless


there is a bacterial superinfection

• In the rare dry cicatricial form, the


nonbleeding ulcers form band-like scars and
lead to digital lymphedema due to
constriction
Clinical Findings
• HIV co-infection may alter the clinical
presentation of GI

• Natural history is usually more rapid, and ulcers


may persist for longer periods, lead to more
tissue destruction, and need more prolonged
antibiotic treatment

• Extragenital dissemination of GI has been


reported in HIV-positive patients
Diagnosis and Laboratory Tests

• Demonstrating the Donovan bodies on smear


or biopsy specimen makes the diagnosis of GI

• Although they are more easily visualized


with properly done smears rather than
biopsy
Tissue smear showing Donovan bodies
which are Gram-negative (A)
Tissue smear showing Donovan bodies
readily stained with Giemsa stain (B)
Diagnosis and Laboratory Tests
• Secondary bacterial infection and debris
may affect the smear result

• It is recommended to wipe the ulcers gently with


cotton swabs first before taking the smear but
not to clean the ulcers with saline first

• Tissue for smear or crush preparations are


better taken from the advancing edge of the
ulcer, and tissue preparation should be made
immediately, before the desiccation of
histiocytes
Diagnosis and Laboratory Tests

• Serology is not helpful in making the


diagnosis

• PCR has so far only been used for


research purposes
Histologically

• Epidermis
Pseudoepitheliomatous hyperplasia and/or
ulcerations, depending on the site biopsied

• Dermis
A dense mixed inflammatory cell infiltrate is
usually seen composed of PMN cells, plasma
cells, histiocytes, and rare lymphocytes. Edema
and endothelial cell swelling are often noted
Acanthosis at the edge of ulce
Abundant Neutrophils at the surface as well as in
intra and sub epidermal location.
Histologically
• Hypertrophic and the cicatricial forms of GI may
exhibit fibrosis.Clusters of Donovan bodies are seen in
the vacuolated cytoplasm of the large mononuclear cells

• Using Giemsa, Wright's, or silver stains, these Donovan


bodies appear as safety-pin–like structures measuring
1 to 2 m x 0.5 to 0.7 m

• These Donovan bodies may also be occasionally found


extracellularly or within neutrophils
Differential diagnosis of Donovan
Bodies

• Frisch bacilli in Mikulicz cells of rhinoscleroma,

• Amastigotes of leishmania,

• Chlamydial inclusion bodies of lymphogranuloma


venereum,

• Histoplasmosis, and

• Michaelis-Gutmann bodies of Malakoplakia


Differential Diagnosis
• Most Likely 

Ulcerative disease of the genital area

• Primary syphilis (hard indolent ulcer) with indolent lymphadenopathy

• Secondary syphilis (pale, white, moist plaques)  

• Lymphogranuloma venereum (prominent inguinal lymphadenopathy)

• Chancroid (painful ulcers with painful lymphadenopathy) Note that


the above diseases may co-exist.
Differential Diagnosis
Always Rule Out 

• Long-standing necrotic lesions of the penis, vulva, or cervix 

• Squamous cell carcinoma

• Genital amebiasis

• Chronic herpes simplex of the immunosuppressed

• Extragenital involvement  

• Leishmaniasis   Scrofuloderma   Deep mycosis Disseminated form with


bone involvement  
• Tuberculosis
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