Granuloma inguinale
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Granuloma inguinale is a
bacteria Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...
l
disease A disease is a particular abnormal condition that negatively affects the structure or function of all or part of an organism, and that is not immediately due to any external injury. Diseases are often known to be medical conditions that a ...
caused by ''
Klebsiella granulomatis ''Klebsiella granulomatis'' is Gram-negative, rod-shaped bacterium of the genus ''Klebsiella'' known to cause the sexually transmitted disease granuloma inguinale (or donovanosis). It was formerly called ''Calymmatobacterium granulomatis''. It ...
'' (formerly known as ''Calymmatobacterium granulomatis'') characterized by
genital ulcer A genital ulcer is an open sore located on the genital area, which includes the vulva, penis, perianal region, or anus. Genital ulcers are most commonly caused by infectious agents (fungal infections, secondary bacterial infections, or sexually t ...
s. It is
endemic Endemism is the state of a species being found in a single defined geographic location, such as an island, state, nation, country or other defined zone; organisms that are indigenous to a place are not endemic to it if they are also found elsew ...
in many less-developed regions. It is also known as donovanosis, granuloma genitoinguinale, granuloma inguinale tropicum, granuloma venereum, granuloma venereum genitoinguinale, lupoid form of groin ulceration, serpiginous ulceration of the groin, ulcerating granuloma of the pudendum, and ulcerating sclerosing granuloma. Oral manifestations are also notably seen. The lesions of oral cavity are usually secondary to active genital lesions. The disease often goes untreated because of the scarcity of medical treatment in the countries in which it is found. In addition, the painless
genital A sex organ (or reproductive organ) is any part of an animal or plant that is involved in sexual reproduction. The reproductive organs together constitute the reproductive system. In animals, the testis in the male, and the ovary in the female, a ...
ulcers can be mistaken for
syphilis Syphilis () is a sexually transmitted infection caused by the bacterium ''Treponema pallidum'' subspecies ''pallidum''. The signs and symptoms of syphilis vary depending in which of the four stages it presents (primary, secondary, latent, an ...
. The ulcers ultimately progress to destruction of internal and external tissue, with extensive leakage of
mucus Mucus ( ) is a slippery aqueous secretion produced by, and covering, mucous membranes. It is typically produced from cells found in mucous glands, although it may also originate from mixed glands, which contain both serous and mucous cells. It is ...
and
blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the c ...
from the highly
vascular The blood vessels are the components of the circulatory system that transport blood throughout the human body. These vessels transport blood cells, nutrients, and oxygen to the tissues of the body. They also take waste and carbon dioxide away f ...
lesions. The destructive nature of donovanosis also increases the risk of
superinfection A superinfection is a second infection superimposed on an earlier one, especially by a different microbial agent of exogenous or endogenous origin, that is resistant to the treatment being used against the first infection. Examples of this in bact ...
by other
pathogen In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a germ ...
ic microbes.


Symptoms and signs

Small, painless nodules appear after about 10–40 days of contact with the bacteria. Later, the nodules burst, creating open, fleshy, oozing lesions. The
infection An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable dise ...
spreads, mutilating the infected tissue. The infection will continue to destroy the tissue until treated. The lesions occur at the region of contact typically found on the shaft of the
penis A penis (plural ''penises'' or ''penes'' () is the primary sexual organ that male animals use to inseminate females (or hermaphrodites) during copulation. Such organs occur in many animals, both vertebrate and invertebrate, but males do n ...
, the
labia The labia are part of the female genitalia; they are the major externally visible portions of the vulva. In humans, there are two pairs of labia: the ''labia majora'' (or the outer labia) are larger and thicker, while the ''labia minora'' are fol ...
, or the
perineum The perineum in humans is the space between the anus and scrotum in the male, or between the anus and the vulva in the female. The perineum is the region of the body between the pubic symphysis (pubic arch) and the coccyx (tail bone), includi ...
. Rarely, the
vagina In mammals, the vagina is the elastic, muscular part of the female genital tract. In humans, it extends from the vestibule to the cervix. The outer vaginal opening is normally partly covered by a thin layer of mucosal tissue called the hymen ...
l wall or
cervix The cervix or cervix uteri (Latin, 'neck of the uterus') is the lower part of the uterus (womb) in the human female reproductive system. The cervix is usually 2 to 3 cm long (~1 inch) and roughly cylindrical in shape, which changes during ...
is the site of the lesion. At least one case in
India India, officially the Republic of India (Hindi: ), is a country in South Asia. It is the seventh-largest country by area, the second-most populous country, and the most populous democracy in the world. Bounded by the Indian Ocean on the so ...
led to partial auto
amputation Amputation is the removal of a limb by trauma, medical illness, or surgery. As a surgical measure, it is used to control pain or a disease process in the affected limb, such as malignancy or gangrene. In some cases, it is carried out on indi ...
of the penis. The patient tested positive for
HIV The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immune ...
-2 and had been infected for six years.


Mechanism

The microorganism spreads from one host to another through contact with the open sores.


Diagnosis

The
diagnosis Diagnosis is the identification of the nature and cause of a certain phenomenon. Diagnosis is used in many different disciplines, with variations in the use of logic, analytics, and experience, to determine " cause and effect". In systems engin ...
is based on the patient's sexual history and on physical examination revealing a painless, "beefy-red ulcer" with a characteristic rolled edge of
granulation tissue Granulation tissue is new connective tissue and microscopic blood vessels that form on the surfaces of a wound during the healing process. Granulation tissue typically grows from the base of a wound and is able to fill wounds of almost any size ...
. In contrast to syphilitic ulcers, inguinal
lymphadenopathy Lymphadenopathy or adenopathy is a disease of the lymph nodes, in which they are abnormal in size or consistency. Lymphadenopathy of an inflammatory type (the most common type) is lymphadenitis, producing swollen or enlarged lymph nodes. In cli ...
is generally mild or absent. Tissue
biopsy A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a diseas ...
and Wright-Giemsa stain are used to aid in the diagnosis. The presence of Donovan bodies in the tissue sample confirms donovanosis. Donovan bodies are rod-shaped, oval organisms that can be seen in the
cytoplasm In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. The ...
of mononuclear phagocytes or
histiocyte A histiocyte is a vertebrate cell that is part of the mononuclear phagocyte system (also known as the reticuloendothelial system or lymphoreticular system). The mononuclear phagocytic system is part of the organism's immune system. The histiocyt ...
s in tissue samples from patients with granuloma inguinale.thefreedictionary.com > Donovan bodies
Retrieved on Nov 29, 2009
They appear deep purple when stained with
Wright's stain Wright's stain is a hematologic stain that facilitates the differentiation of blood cell types. It is classically a mixture of eosin (red) and methylene blue dyes. It is used primarily to stain peripheral blood smears, urine samples, and bone marr ...
. These intracellular inclusions are the encapsulated Gram-negative rods of the causative organisms. They were discovered by
Charles Donovan Charles Donovan MD (19 September 1863 – 29 October 1951) was an Irish medical officer in the Indian Medical Service. He is best remembered for his discoveries of ''Leishmania donovani'' as the causative agent of visceral leishmaniasis, and ''Kl ...
.


Classification

The first known name for this condition was "serpiginous ulcer", which dates to 1882. The proper clinical designation for donovanosis is "granuloma inguinale". A
granuloma A granuloma is an aggregation of macrophages that forms in response to chronic inflammation. This occurs when the immune system attempts to isolate foreign substances that it is otherwise unable to eliminate. Such substances include infectious ...
is a nodular type of inflammatory reaction, and inguinale refers to the inguinal region, which is commonly involved in this infection. The disease is commonly known as donovanosis, after the Donovan bodies seen on microscopy, which are a diagnostic sign. The causative organism, ''
Klebsiella granulomatis ''Klebsiella granulomatis'' is Gram-negative, rod-shaped bacterium of the genus ''Klebsiella'' known to cause the sexually transmitted disease granuloma inguinale (or donovanosis). It was formerly called ''Calymmatobacterium granulomatis''. It ...
'', was called ''Calymmatobacterium granulomatis'', and some sources still use this classification, from the Greek ''kalymma'' (a hood or veil), referring to the lesions that contain the bacteria. Prior to this, it was called ''Donovania granulomatis'', named after the Donovan bodies. The
specific Specific may refer to: * Specificity (disambiguation) * Specific, a cure or therapy for a specific illness Law * Specific deterrence, focussed on an individual * Specific finding, intermediate verdict used by a jury in determining the fina ...
name ''granulomatis'' refers to the granulomatous lesions. The organism was recently reclassified under the
genus Genus ( plural genera ) is a taxonomic rank used in the biological classification of extant taxon, living and fossil organisms as well as Virus classification#ICTV classification, viruses. In the hierarchy of biological classification, genus com ...
''Klebsiella'', a drastic
taxonomic Taxonomy is the practice and science of categorization or classification. A taxonomy (or taxonomical classification) is a scheme of classification, especially a hierarchical classification, in which things are organized into groups or types. ...
change since it involved changing the organism's
phylum In biology, a phylum (; plural: phyla) is a level of classification or taxonomic rank below kingdom and above class. Traditionally, in botany the term division has been used instead of phylum, although the International Code of Nomenclature f ...
. However,
polymerase chain reaction The polymerase chain reaction (PCR) is a method widely used to rapidly make millions to billions of copies (complete or partial) of a specific DNA sample, allowing scientists to take a very small sample of DNA and amplify it (or a part of it) t ...
techniques using a
colorimetric Colorimetry is "the science and technology used to quantify and describe physically the human color perception". It is similar to spectrophotometry, but is distinguished by its interest in reducing spectra to the physical correlates of color ...
detection system showed a 99% similarity with other species in the genus ''Klebsiella''. The clinical appearances of this lesion orally are classified into three types: Ulcerative, exuberant, cicatricial.


Prevention

The disease is effectively treated with
antibiotics An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention o ...
, therefore,
developed countries A developed country (or industrialized country, high-income country, more economically developed country (MEDC), advanced country) is a sovereign state that has a high quality of life, developed economy and advanced technological infrastruct ...
have a very low incidence of donovanosis; about 100 cases are reported each year in the United States. However, sexual contact with individuals in endemic regions dramatically increases the risk of contracting the disease. Using condoms,
sexually transmitted disease Sexually transmitted infections (STIs), also referred to as sexually transmitted diseases (STDs) and the older term venereal diseases, are infections that are spread by sexual activity, especially vaginal intercourse, anal sex, and oral ...
testing before beginning a sexual relationship, and avoidance of these sexual contacts are effective preventative measures for donovanosis.


Treatment

Recommended regimen is
azithromycin Azithromycin, sold under the brand names Zithromax (in oral form) and Azasite (as an eye drop), is an antibiotic medication used for the treatment of a number of bacterial infections. This includes middle ear infections, strep throat, pneumon ...
1 gram oral/iv once per week, alternatively
doxycycline Doxycycline is a broad-spectrum tetracycline class antibiotic used in the treatment of infections caused by bacteria and certain parasites. It is used to treat bacterial pneumonia, acne, chlamydia infections, Lyme disease, cholera, typhus, an ...
100 mg orally twice a day or
ciprofloxacin Ciprofloxacin is a fluoroquinolone antibiotic used to treat a number of bacterial infections. This includes bone and joint infections, intra abdominal infections, certain types of infectious diarrhea, respiratory tract infections, skin infec ...
750 mg orally twice a day or
erythromycin Erythromycin is an antibiotic used for the treatment of a number of bacterial infections. This includes respiratory tract infections, skin infections, chlamydia infections, pelvic inflammatory disease, and syphilis. It may also be used duri ...
base 500 mg orally four times a day or
trimethoprim-sulfamethoxazole Trimethoprim/sulfamethoxazole, sold under the brand name Bactrim among others, is a fixed-dose combination antibiotic medication used to treat a variety of bacterial infections. It consists of one part trimethoprim to five parts sulfamethoxazo ...
one double-strength (160 mg/800 mg) tablet orally twice a day. All antibiotic regimens should last for at least 3 weeks and until all lesions have completely healed. Normally, the infection will begin to subside within a week of treatment, but the full treatment period must be followed to minimize the possibility of relapse. The CDC 2015 guidelines give azithromycin as the antibiotic of choice.


See also

* Chancroid *
List of cutaneous conditions Many skin conditions affect the human integumentary system—the organ system covering the entire surface of the body and composed of skin, hair, nails, and related muscle and glands. The major function of this system is as a barrier against t ...


References


Further reading

* Gavin Hart MD, MP
Transcript
of the lecture given at the Australian Society for Infectious Diseases/Australasian College of Tropical Medicine Conference at Palm Cove (Cairns), Queensland on 19 April 1999.


External links


Research supporting Klebsiella Genus classification
{{DEFAULTSORT:Granuloma Inguinale Bacterial diseases Bacterium-related cutaneous conditions Infections with a predominantly sexual mode of transmission