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The nodular type consists of soft lumps that are typically beefy red in colour and tend to bleed
easily. These are usually painless despite ulceration.
The hypertrophic or verrucous type consists of large dry warty masses that resemble genital
warts.
The necrotic type presents as dry ulcers that evolve into scarred areas .
Complications such as bleeding, secondary infection and swelling (lymphoedema) may occur. Local lymph
nodes may be enlarged and may become abscesses or ulcers as the infection spreads into the overlying
skin.
In the early stages it may be difficult to differentiate granuloma inguinale from chancroid. In the later
stages, the condition may look like lymphogranuloma venereum. It may also be confused with other
conditions, such as penile or vulvar cancer or syphilis.
Granuloma inguinale
If there are no signs of healing within the first few days of treatment with initial antibiotic
therapy, the addition of intravenous gentamicin may be necessary.
Sexual activity should not take place until all lesions are completely healed. Follow-up examination is
necessary to ensure a complete recovery.
If granuloma inguinale is left untreated or treatment is delayed it may cause widespread destruction of
the genitals and leave permanent swelling and scarring. Infection may also spread to other parts of the
body and cause secondary problems such as pneumonia or heart failure.
Part 1 of 6: Overview
In the first stage, the small pimple will begin to spread and eat away
at the surrounding tissue. As the tissue begins to wear away, it turns
pink or a faint red. The bumps then turn into raised red nodules with a
velvety texture. This happens around the anus and genitals. Although
the bumps are painless, they can bleed if they are injured.
Stage Two
In the second stage of the disease, bacteria begin to erode the skin.
Once this occurs, you will develop shallow ulcers that will spread from
the genitals and anus to the thighs and lower abdomen (inguinal
area). You will notice that the perimeters of the ulcers are lined with
granulated tissue. A foul smell may accompany the ulcers.
Stage Three
Medscape
Granuloma Inguinale (Donovanosis)
Author: Jerry J Fasoldt, MD; Chief Editor: Dirk M Elston, MD
Background
Granuloma inguinale is a chronic bacterial infection that frequently is associated with other sexually transmitted
diseases. Granuloma inguinale is characterized by intracellular inclusions in macrophages referred to as Donovan
bodies. Granuloma inguinale usually affects the skin and mucous membranes in the genital region, where it results
in nodular lesions that evolve into ulcers. The ulcers progressively expand and are locally destructive, as
demonstrated in the image below.
Pathophysiology
The intracellular organism responsible for granuloma inguinale was initially described by Donovan over a century
ago, and subsequently, the bacterium was classified in 1913 as Calymmatobacterium granulomatis. Although
Anderson suggested that the organism be eponymously named Donovania granulomatosis, Carter et al
discovered that the molecular structure of the causative organism was similar to Klebsiella species and
reclassified the gram-negative pleomorphic bacillus as Klebsiella granulomatis.[1, 2]
The mode of transmission of granuloma inguinale primarily occurs through sexual contact; however, it is
hypothesized to have low infectious capabilities because repeated exposure is necessary for clinical infection to
occur. Additionally, granuloma inguinale may also be obtained through the fecal route or by passage through an
infected birth canal.
Epidemiology
Frequency
United States
Fewer than 100 cases of granuloma inguinale are reported annually, many of which are thought to be acquired
during foreign travel.
International
Granuloma inguinale is rare in temperate climates, but it is common in the tropics and subtropics. Granuloma
inguinale is endemic in Western New Guinea, the Caribbean, Southern India, South Africa, Southeast Asia,
Australia, and Brazil.
Mortality/Morbidity
If granuloma inguinale remains untreated, secondary infections and lymphedema/elephantiasis may occur.
Persistent granuloma inguinale lesions continue to expand and are locally destructive. Treated granuloma
inguinale lesions tend to exhibit extensive fibrosis, resulting in strictures. Squamous cell carcinomaand less
often basal cell carcinoma can develop in long-standing lesions and/or scars. Also see Complications.
Race
The incidence is higher in blacks than in whites in the United States. The incidence is higher in native persons
than in Europeans in Western New Guinea. The incidence is higher in Hindus than in Muslims in India. These
differences are more likely the result of disparities in socioeconomic status and living conditions than of a racial
susceptibility.[3]
Sex
No sexual predominance is reported for granuloma inguinale.
Age
Granuloma inguinale most commonly is seen in sexually active people aged 20-40 years.
History
Although the exact incubation period for granuloma inguinale is unknown, it ranges from a day to a year, with the
median time being 50 days. [3]
Physical
Morphology
The 4 main types of cutaneous lesions are as follows:
Nodular: The initial granuloma inguinale lesion is a papule or nodule that arises at the site of inoculation.
The nodule is soft, often pruritic and erythematous, and eventually ulcerates. A nodule may be mistaken for a
lymph node [ie, pseudobubo].
Ulcerovegetative (most common): These granuloma inguinale lesions develop from nodular lesions and
consist of large, usually painless, expanding, suppurative ulcers. The ulcers have clean, friable bases with
distinct, raised, rolled margins and have a tendency to bleed easily. The ulcers are "beefy red" and slowly
expand centrifugally, eventually becoming more granulomatous with serpiginous borders. They are commonly
located in the skin folds, and autoinoculation is a common feature, resulting in lesions on adjacent skin. Ulcers
often become secondarily infected with other types of bacteria and emit a putrid odor.
Cicatricial: Dry ulcers evolve into cicatricial plaques and may be associated with lymphedema.
Hypertrophic or verrucous (relatively rare): This proliferative reaction, with the formation of large
vegetating masses, may resemble genital warts.
Elephantiasislike swelling of the external genitalia is a frequent complication and is found most often in infected
females in the late stage of granuloma inguinale.
Note the clinical penile images below.
MD.
Distribution
The most common locations of granuloma inguinale lesions in men are the sulcocoronal and
balanopreputial regions, as well as the anus.
In women, granuloma inguinale lesions occur on the labia minora, the mons veneris, the fourchette,
and/or the cervix. Cervical involvement occurs in 10% of cases.
Children are frequently infected via contact with an adult; however, this is not necessarily the result of
sexual abuse.[3]
Extragenital involvement
Causes
Granuloma inguinale is caused by Klebsiella granulomatis, a gram-negative pleomorphic bacillus formerly known
as Calymmatobacterium granulomatis.
Diagnostic Considerations
Mycobacterial infection
Cutaneous tuberculosis
Ovarian cancer[4] : One case report describes a patient with chronic granuloma inguinale (donovanosis)
who presented with recurrent abdominal pain. Results of abdominal computed tomography (CT) scanning showed
pelvic masses that mimicked ovarian cancer.
Carcinoma of the cervix: One report describes cervical donovanosis, which, on an MRI, was
indistinguishable from carcinoma of the cervix. [5]
Differential Diagnoses
Chancroid
Herpes Simplex
Lymphogranuloma Venereum
Syphilis
Laboratory Studies
Although isolation of Klebsiella granulomatis has been reported, the organism is extremely fastidious and
culture is beyond the capability of most laboratories. The easiest method to visualize the organism is via smears
from the base of the ulcer. The organisms are seen within the cytoplasm of histiocytes. Characteristically, they
exhibit bipolar staining, which has been likened to a safety-pin appearance, and are referred to as Donovan
bodies. The organisms can occasionally be identified in tissue biopsy specimens with the use of special stains.
If a quick diagnosis is necessary, a smear can be performed. First, a cotton swab is gently rolled
over the ulcer so as not to cause bleeding. The swab is then rolled over a glass slide. The slide is allowed to air
dry and is then stained with Giemsa stain or pinacyanol to demonstrate Donovan bodies.
Alternatively, a crush preparation can be performed. A small piece of tissue should be obtained
from the ulcer edge or base via punch biopsy, curettage, or a thin wedge resection. Next, the tissue is crushed
between 2 glass slides, separated, and then air dried. A Wright-Giemsa, Warthin-Starry, toluidine blue, or
Leishman stain may be used to demonstrate the Donovan bodies.
Lastly, a tissue biopsy specimen can be obtained; however, the organisms may be difficult to find
in early or secondarily infected lesions, or on routine stained sections with hematoxylin and eosin. Thin, paraffinembedded sections stained with Giemsa or silver stain may facilitate identification of the rod-shaped,
encapsulated organisms within the macrophages.
Polymerase chain reaction techniques may be more sensitive ; however, they are currently only used for
scientific research.
An indirect immunofluorescent technique is available to test serum; however, it is not accurate enough for
confirmatory diagnosis.
Culture of Klebsiella granulomatis from feces has been reported using a monocyte co-culture system and
a modified Chlamydia culture.
Papanicolaou smears may identify Donovan bodies in patients undergoing routine cervical cytological
screening.
A British Association for Sexual Health and HIV (BASHH) clinical guideline summary is Donovanosis
(granuloma inguinale). In: Sexually transmitted infections: UK national screening and testing guidelines.[6]
Imaging Studies
If bony involvement is suspected in granuloma inguinale, radiography or other imaging studies are
indicated.
Other Tests
Testing for other sexually transmitted diseases is warranted because multiple coexisting infections are
common.
Histologic Findings
The epidermis displays acanthosis at the ulcer edge, with pseudoepitheliomatous hyperplasia variably present. A
dense dermal infiltrate of histiocytes and plasma cells is present, with a scattering of small neutrophilic abscesses.
The macrophages are large and vacuolated, and they contain intracellular bacilli (ie, Donovan bodies), which are
best visualized using special stains such as a Warthin-Starry, Wright-Giemsa, or Leishman stain. Klebsiella
granulomatis does not stain well with hematoxylin and eosin.
Medical Care
The recommended antibiotic for granuloma inguinale is either trimethoprim/sulfamethoxazole [7] or doxycycline.
Alternatives include ciprofloxacin, erythromycin, or azithromycin. [8] The antibiotic should be given for at least a 3week course and continued until reepithelialization of the ulcer occurs and any signs of the disease have resolved.
If the granuloma inguinale ulcers do not respond within the first days of therapy, add an aminoglycoside (eg,
gentamicin at 1 mg/kg IV q8h). Relapse of granuloma inguinale may occur up to 18 months after treatment. In
some countries, tetracycline is no longer recommended, owing to bacterial resistance. [9]
Special considerations
Pregnancy and HIV-associated granuloma inguinale are special concerns in the treatment of this condition. The
addition of a parenteral aminoglycoside (eg, gentamicin) to the treatment regimen should be considered for
pregnant women and for persons with HIV-associated granuloma inguinale.
Pregnancy is a relative contraindication for the use of sulfonamides. In pregnant and lactating women with
granuloma inguinale, the Centers for Disease Control and Prevention [10] recommends erythromycin with or without
a parenteral aminoglycoside; however, recent data suggest erythromycin may increase the risk of congenital
malformation.[11] Doxycycline and ciprofloxacin are contraindicated in pregnancy.
HIV-associated granuloma inguinale may take longer to heal, and the addition of a parenteral aminoglycoside to
the regimen is highly recommended.[12] Note that malignant transformation and autoamputation have both been
reported in HIV-positive patients with granuloma inguinale.[13, 14]
Sexual contacts within 60 days prior to the onset of the patient's symptoms of granuloma inguinale should be
examined and offered therapy.
A clinical guideline summary is available from the US Centers for Disease Control and Prevention: Diseases
characterized by genital ulcers. Sexually transmitted diseases treatment guidelines 2006.[15]
Surgical Care
Once granuloma inguinale is healed, disfiguring genital swellings may need to be surgically corrected.
Medication Summary
The goal of pharmacotherapy for granuloma inguinale is to reduce morbidity and to prevent complications.
Antibiotics
Class Summary
Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the
clinical setting.
View full drug information
Ciprofloxacin (Cipro)
Bactericidal fluoroquinolone antibiotic that inhibits the bacterial enzymes topoisomerase II (DNA gyrase) and
topoisomerase IV, which are required for bacterial DNA replication, transcription, repair, and recombination.
View full drug information
Azithromycin (Zithromax)
Azalide antibiotic (subclass of macrolide antibiotics) that inhibits bacterial protein synthesis by binding 50S
ribosomal subunits of susceptible organisms; may be bacteriocidal or bacteriostatic depending on concentration
and type of microorganism.
Deterrence/Prevention
Positive strides have been made in reducing the incidence of granuloma inguinale in endemic regions.
Australia and its surrounding indigenous areas have witnessed a decrease in the incidence of
granuloma inguinale through the establishment of a National Donovanosis Eradication Advisory Committee. The
committee consists of project officers representing different geographic areas who work closely with primary care
healthcare providers.
The goal is to develop educational materials, conduct in-service teaching for staff in rural and
remote areas, implement common protocols for treatment and diagnosis, and undertake active surveillance.
Since the development of the committee in 2001, the number of new cases of granuloma inguinale has fallen to
the lowest levels since the commencement of accurate epidemiological data collection.
This committee represents a proven model of public health intervention, using centralized officers
with expertise in sexually transmitted infection who liaise with primary healthcare providers. A similar model may
help reduce the incidence of disease in other endemic areas. [16]
Complications
The most serious complication of granuloma inguinale is carcinoma, which is reported to occur in 0.25%
of patients. This includes squamous cell carcinoma andbasal cell carcinoma. Of note, squamous cell carcinoma is
sometimes difficult to histologically distinguish from pseudoepitheliomatous hyperplasia associated with the
lesions of granuloma inguinale. Furthermore, it is possible for granuloma inguinale and squamous cell carcinoma
to coexist in the same lesion.[17]
Once the lesions have healed, extensive fibrosis, stricture formation, and phimosis, leading to significant
deformity and functional disability, may occur.
Elephantiasis of the genitals may develop secondary to lymphatic destruction.
Granuloma inguinale may also progress to involve extragenital sites, with potentially fatal systemic spread
to the viscera.
Granuloma inguinale also increases the risk of acquiring HIV, and the risk is augmented with chronic
lesions. Co-infection with HIV results in persistent ulcers that require intensive prolonged treatment with
antibiotics.[3]
Autoamputation of the penis has been reported in a man with long-standing granuloma inguinale
associated with underlying HIV-2 infection.[13]
Prognosis
Patient Education
For excellent patient education resources, visit eMedicineHealth's Sexual Health Center and Pregnancy
Center. Additionally, see eMedicineHealth's patient education articles Sexually Transmitted Diseases, Birth Control
Overview, andBirth Control Methods.
GRANULOMA INGUINALE
(Donovanosis)
1.
Identifikasi
Granuloma inguinale adalah penyakit menular yang disebabkan oleh bakteri, menyerang kulit dan selaput lendir
genitalia externa, daerah inguinal dan anal. Penyakit ini berlangsung kronis, progresif dan destruktif,
penularannya sangat lambat. Penyakit ditandai dengan munculnya nodula, papula menyebar secara pelahalahan, tidak lunak, exuberant, granulomatous, ulcerative dan terjadi pembentukan jaringan parut.
Lesi berbentuk khas berupa granuloma berwarna merah seperti daging sapi, meluas kepinggir dengan ciri khas
pada ujungnya menggulung dan akhirnya membentuk jaringan ikat. Lesi tidak mudah remuk (nontriable). Lesi
biasanya muncul pada bagian-bagian tubuh yang hangat dan lembab, misalnya didaerah lipat paha, daerah
perianal, serotum, vulca dn vagina. Hampir 90% daerah yang terkena adalah daerah genitalia, daerah inguinal
sekitar
10%,
daerah
anal
sekitar
1-5%.
Apabila tidak diobati penyakit ini sangat destruktif dan dapat merusk struktur alat kelamin dan menyebar
denan cara auto inokulasi kebagian lain dari tubuh. Diagnosa ditegakkan dengan pemeriksaan laboratorium
yaitu dengan ditemukannya Donovan bodies yaitu organisme berbentuk batang didalam sitoplasma. Donovan
bodies dapat dilihat pad preparat jaringn granulasi yag diwarnai dengan pengecatan Wright atau Giemsa.
Pemeriksaan histologis juga dapat dilakukan terhadap jaringan biopsi. Tanda phatoguonomis dan penyakit ini
adalah pada pemeriksaan mikroskopis sel-sel mononuklear yang terinfeksi dipenuhi dengan Donovan
bodies.Tidak dilakukan kultur, oleh karena sangat sulit dilakukan. Pemeriksaan serologis dan pemeriksaan PCR
hanya dilakukan untuk tujuan penelitian. Untuk menyingkirkan kemungkinan infeksi disebabkan oleh
Haemophilus
ducrey
dapat
dilakukan
dengan
kultur
menggunakan
media
selektif.
2.
Penyebab
Penyakit
Calymmatobacterium granulomatis (Donovania granulomatis), basil gram negatif, diduga sebagai penyebab,
namun
belum
pasti.
3.
Distribusi
Penyakit
Jarang ditemukan di negara maju (jarang ditemukan di Amerika Serikat, KLB kadang-kadang juga terjadi).
Penyakit ini endemis di wilayah tropis dan subtropis seperti: India Selatan, Papua Nugini, Australia tengah dan
utara, kadang-kadang Amerika Latin, Kepulauan Karibia, Afrika bagian tengah dan timur selatan. Lebih sering
ditemukan pada pria daripada wanita dan pada orang dengan status sosial ekonomi rendah; dapat terjadi pada
anak
berumur
1-4
tahun,
tetapi
paling
dominan
pada
usia
20-40
tahun.
4.
Reservoir: Manusia.
5.
Cara
Penularan
Diduga melalui kontak langsung dengan lesi selama melakukan hubungan seksual tetapi dalam berbagai studi
hanya 20-65% pasangan seksual yang terinfeksi, ada beberapa kasus penularan bukan melalui hubungan
seksual.
6.
Masa
Inkubasi: Tidak
diketahui,
mungkin
antara
sampai
16
minggu.
7.
Masa
Penularan
Tidak diketahui, penularan mungkin tetap berlangsun selama masih ada lesi terbuka pada kulit atau membrana
mukosa.
8.
Kerentanan
sangat
Kerentanan
bervariasi,
9.
tidak
terbentuk
dan
setelah
mendapatkan
Cara-cara
Kekebalan
infeksi.
Pemberantasan
A.
Upaya
Pencegahan
Kecuali cara-cara yang dapat diterapkan hanya untuk sifilis, maka cara-cara penanggulangan untuk sifilis,
seperti yang diuraikan pada 9A berlaku juga untuk pencegahan granuloma inguinalae. Program penyuluhan
kesehatan masyarakat pada daerah endemis ditekankan mengenai pentingnya diagnosa dini dan pengobatan
dini.
B.
Penanganan
Penderita,
Kontak
dan
Lingkungan
sekitar
1) Laporan kepada instansi kesehatan setempat: Penyakit ini wajib dilaporkan di semua negara bagian di
Amerika Serikat dan negara lain
2) Isolasi: Tidak ada, hindari
didunia,
kontak
Kelas
yang
3) Disinfeksi serentak: Disinfeksi dilakukan terhadap discharge dari lesi dan terhadap barang-barang yanga
tercemar.
4)
Karantina:
Tidak
ada.
5) Imunisasi Kontak: Tidak dilkakukan, berikan pengobatan dengan segera apabila secara klinis dicurigai telah
terjadi
6) Investigasi
kontak
dan
sumber
infeksi:
Lakukan
pemeriksaan
terhadap
kontak
infeksi.
seksual.
7) Pengobatan spesifik: Erythromycin, TP-SMX dan doxycycline, dilaporkan cukup efektif tetapi strain resisten
terhadap obat dapat terjadi. Pengobatan diteruskan selama 3 minggu sampai lesi sembuh, kambuh jarang
terjadi tetapi kalau terjadi maka respons terhadap pengobatan kedua kurang. Dosis tunggal dengan cefriaxone
IM atau ciprofloxacin PO dilaporkan juga cukup efektif.
Granuloma inguinale (GI) adalah peny. infeksi oleh bakteri yg sifatnya kronik, progressif, cukup
infeksius, yg menyebabkan destruksi permukaan & pembentukan granuloma di kulit & jar. subkutan,
umumnya ditularkan melalui hub. seksual.
ETIOLOGI
GI, peny. yg disebabkan oleh Calymatobacterium granulomatosis yg merupakan bakteri Gram
negatif dgn ukuran 1,5 m x 0,7 m, pleomorfik, dan non motil.
Bakteri ini harus diisolasi dlm yolk sac embrio ayam, walaupun kemudian diketahui dpt juga tumbuh
pada medium yg mengandung kuning telur.
Ulkus granulomatous
Tipe yg paling umum & paling sering ditemukan, berwarna merah terang, seperti
daging.
Non tender ulcer yg mudah berdarah saat penyentuhan & menjadi semakin parah bila tdk diterapi.
2.
Tipe ini terdiri dari ulkus bertepi verukoid atau ireguler yg meninggi, dengan dasar granulomatous.
Tumbuh dengan tepi yg ireguler, biasanya sangat kering & dpt terjadi edema.
3.
Nekrotik
Kekeringan, sklerosis atau lesi sikatriks dengan jaringan fibrous dan parut.
Secara anatomi area yg terkena pada pria sulkus koronarius, regio subpreputium, dan anus, wanita,
labium mayora, serviks & traktus genital atas. GI juga dpt mengenai tulang & hepar walaupun jarang &
hal ini biasanya berhubungan dgn kehamilan & infeksi servikal. Lesi primer bisa titik seperti papul,
nodul subkutan /ulkus.
Percobaan inokular pada manusia menghasilkan lesi sesudah 21 hari.
PEMERIKSAAN PENUNJANG
Puncak konsentrasi metophrim dlm darah terjadi dalam 2 jam sedangkan sulfamethoxasole dlm
Jika 800 mg sulfamethoxasole diberikan dgn 160 mg trimetoprim 2 x/hr, maka puncak
Ampisilin.
Gentamisin.
Tetrasiklin.
Dianjurkan : 500 mg 4 x/hr, selama 10 20 hari. Tetrasiklin drug of choice untuk GI.
Tetrasiklin bersifat bakteriostatik, apabila diberikan dosis tunggal peroral puncak konsentrasi
tercapai dlm 2 4 jam. Tetrasiklin mempunyai waktu paruh 6 12 jam dianjurkan penggunaannya 2- 4
x/hr.
Penggunaan 250 mg setiap 6 jam menghasilkan konsentrasi plasma 2 2,5 ug/ml.
5.
Eritromisin.
Kloramfenikol.
Terapi Topikal
Dpt diberikan kompres hangat dgn kompleks iodim polivynilpyrolidone, quinolol sulfat / dgn
potassium permanganat.
Sekalipun tanda-tanda penyembuhan lesi sudah terjadi seminggu setelah R/, terapi tetap perlu
Dapat dilakukan pada komplikasi GI seperti elefantiasis, striktur dan abses pelvis.