Practice Essentials
Chancroid is a sexually transmitted genital ulcer disease (GUD) caused by the gram-negative bacillus Haemophilus ducreyi. H ducreyi produces skin lesions in children that resemble ulcers associated with the tropical disease yaws. [1, 2] However, in adults, chancroid is characterized by the presence of painful ulcers (see image below) and inflammatory inguinal adenopathy. [3] Multiple nonindurated ulcers with ragged edges may develop around the initial ulcer. Painful inguinal lymphadenitis (bubo) can develop, and the lymph node may suppurate and drain to the skin, resulting in ulceration. [4]
In most areas of the United States, chancroid cases are mandatorily reportable to health departments.
Chancroid usually starts as a small papule that rapidly becomes pustular and eventually ulcerates. The ulcer enlarges, develops ragged undermined borders, and is surrounded by a rim of erythema. Unlike syphilis, lesions are tender and the border of the ulcer is not indurated. Courtesy of Hon Pak, MD.
Chancroid is often referred to as a soft chancre because the lesions are usually not indurated. In contrast, a syphilitic chancre is nontender and indurated. The identification of the causative agent of chancroid was first reported in 1889 by August Ducrey, following experiments in which he autoinoculated patients' forearms with pus from their genital ulcers. [5, 6, 7]
Causes
H ducreyi (a short gram-negative bacillus) causes chancroid. See Pathophysiology. Chancroid is closely associated with prostitution. H ducreyi can survive only in subgroups of the population with a sufficient turnover of sex partners. Chancroid is not a sustainable infection in sexual networks with low rates of partner change.
Diagnosis
A probable chancroid diagnosis can be made if all the following criteria are met [8, 9, 10] :
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The patient has 1 or more painful genital ulcers.
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The patient has no evidence of Treponema pallidum infection by darkfield examination of ulcer exudate or by serologic testing for syphilis performed at least 7 days after the onset of ulcers.
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The clinical presentation, the appearance of genital ulcers, and, if present, the presence of regional lymphadenopathy are typical for chancroid.
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Test results for herpes simplex virus (HSV) performed on the ulcer exudate are negative. [11]
The combination of a painful ulcer and tender inguinal adenopathy, symptoms occurring in one third of patients, suggests a diagnosis of chancroid; when accompanied by suppurative inguinal adenopathy, these signs are almost pathognomonic.
Prognosis
The prognosis is excellent if chancroid is treated properly and if no co-infection with HIV is present. As many as 5% of patients have a chancroid relapse and usually respond to a repeat course of their original therapy. No adverse effects of chancroid on pregnancy outcome have been reported. Phimosis, balanoposthitis, and rupture of buboes with fistula formation and scarring are reported complications of chancroid.
Treatment
See Treatment.
Pathophysiology
H ducreyi produces a potent cytolethal distending toxin, which is an important virulence factor in the pathogenesis of chancroid, probably contributing to both the generation and the slow healing of ulcers. [12, 13, 14, 15]
H ducreyi contains a fimbrialike protein (Flp) operon that encodes proteins that contribute to adherence and pathogenesis. The production and secretion of 3 Flp proteins, Flp1, Flp2, Flp3, has been demonstrated to contribute to microcolony formation and attachment to human foreskin fibroblasts cells in vitro. [16] In a small human trial, injection of a deletion mutant that lacked expression of all 3 Flp proteins into volunteers demonstrated significantly reduced size of papule formation, as well as pustule formation rate. [17]
Chancroid, or soft chancre, facilitates human immunodeficiency virus (HIV) transmission. The chemokine receptors CCR5 and CXCR4 belong to the class of 7 transmembrane G-protein–coupled receptors, and their natural ligands are key players in the recruitment of immune cells to sites of inflammation. CCR5 and CXCR4 are the 2 main co-receptors essential for HIV entry. Macrophages in chancroid lesions have significantly increased expression of CCR5 and CXCR4 compared with peripheral blood cells, and CD4 T cells have significant up-regulation of CCR5. The beta-chemokine RANTES (regulated on activation, normal T cell expressed and secreted) are important ligands for CCR5. RANTES is present throughout the papular and pustular stages of chancroid infection but is not present in uninfected control skin. [18]
Host polymorphisms in TLR9 and IL10 may alter manifestations of the disease. [19]
Together with the disruption of mucosal and skin barriers, the presence of cells with up-regulated HIV-1 co-receptors in H ducreyi –infected lesions provides an environment that facilitates the acquisition of HIV-1 infection. Effective and early treatment of genital ulceration, and chancroid in particular, may help to control the spread of HIV infection in tropical countries [20] ; however, at present, evidence to determine whether this will significantly reduce the risk of HIV acquisition is insufficient. [21, 22]
Epidemiology
Frequency
Chancroid is rarely reported in the United States, but regional outbreaks and some endemic transmission occur, principally among migrant farm workers and poor inner-city residents. [23] In 2016, just 7 chancroid cases in 6 states were reported to the Centers for Disease Control and Prevention (CDC). [24]
Because of a lack of readily available, accurate diagnostic tests, the global incidence of chancroid is unknown. An estimated 6 million cases of chancroid were documented to occur each year; however, this has declined over the last decade in formal endemic areas. [25] Chancroid is common in many of the world's poorest regions such as areas of Africa, Asia, and the Caribbean. These regions also have some of the highest rates of HIV infection in the world, and chancroid is common in all 18 countries where adult HIV prevalence surpasses 8%. In addition to regional outbreaks, individual cases are reported sporadically in the developed world, usually in individuals who have recently returned from chancroid-endemic areas or occasionally within the context of localized urban outbreaks, which may be associated with commercial sex work.
The first recorded case of chancroid in the Czech Republic (now Czechia) was reported in 2018. The patient was an adult, HIV positive, heterosexual male. [26]
Sex
Males develop chancroid most often, with a male-to-female ratio of 3-25:1. [27] Uncircumcised men develop chancroid more often than circumcised men. [28] Patients who are uncircumcised do not respond to treatment as well as those who are circumcised. [29, 30] Chancroid is more common in heterosexual men. [31]
Female prostitutes, either with active disease in the form of genital ulcers or as asymptomatic carriers, are an important reservoir for chancroid infection.
Age
Chancroid is most prevalent in sexually active and promiscuous males, with a mean patient age of 30 years.
Prognosis
Chancroid produces painful ulcers on the genitals, often (50%) associated with unilateral tender inguinal lymphadenitis (ie, a bubo). Left untreated, the buboes can form fluctuant abscesses that spontaneously rupture, resulting in a nonhealing ulcer.
Painful inguinal lymphadenitis may develop 1-2 weeks after the presentation of ulcers. [4]
Chancroid has been shown to be a major cofactor in the transmission of HIV-1 infection. [32] This relationship has been especially significant in the heterosexual spread of HIV in Africa. [20, 33] Chancroid-infected patients who have HIV should be monitored closely because they are more likely to experience treatment failure and to have ulcers that heal slowly.
Patient Education
The patient should be strongly advised to avoid sexual contacts while the ulcers are open because they are highly infectious and may cause a community outbreak.
Patients should be advised to avoid prostitutes, to use condoms, and to avoid having multiple partners.
Cocaine and alcohol abuse should be addressed because both contribute to higher rates of the disease.
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Chancroid usually starts as a small papule that rapidly becomes pustular and eventually ulcerates. The ulcer enlarges, develops ragged undermined borders, and is surrounded by a rim of erythema. Unlike syphilis, lesions are tender and the border of the ulcer is not indurated. Courtesy of Hon Pak, MD.
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This patient shows the characteristic lesions of chancroid. The bubo on the right side drained spontaneously. The bubo in the left inguinal canal required needle aspiration.
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Close-up view of chancroid ulcers.
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Large fluctuant buboes should be drained with the patient under local anesthesia and a large-gauge needle inserted through surrounding healthy skin. The insertion site should be superior or lateral to the bubo to prevent chronic drainage from the site.
