Background
Chancroid is a genital ulcerative disease and sexually transmitted infection characterized by soft (nonindurated) ulcers with irregular borders and tender inguinal lymphadenopathy, or buboes. The causative organism, Haemophilus ducreyi, is a gram-negative, anaerobic, coccobacillus that is notable for its complex growth requirements. [1]
The bacterium was first identified by Auguste Ducrey in 1889 following the autoinoculation of patients’ forearms with purulent material obtained directly from their genital ulcers. These studies provided the foundation for the differentiation of chancroid from syphilis, at least in etiology, as autoinoculation of the later did not result in ulcer formation. [2] H ducreyi is strictly a human pathogen, without an identified reservoir and mostly acts extracellularly. [3, 4]
Pathophysiology
H ducreyi enters the skin through a break in the epithelium, usually microabrasions, following minor trauma such as that experienced during sexual intercourse. Once the bacteria have breached the integument, they recruit a host of inflammatory cells to the inoculated area, including polymorphonuclear neutrophils (PMNs), macrophages, dendritic cells, natural killer cells, and CD4 and CD8 cells. [5] The bacteria also induce the secretion of interleukin 6 (IL-6) and interleukin 8 (IL-8) from cells of the epidermis and dermis (keratinocytes, fibroblasts, endothelial cells, and melanocytes). IL-8, in turn, induces PMNs and macrophages to form abscesses, appreciated clinically as intradermal pustules. Simultaneously, IL-6 stimulates CD4 cell activity in the area through the up-regulation of T-cell interleukin 2 (IL-2) receptor expression.
The formation of the characteristic ulcers seen in chancroid is facilitated by H ducreyi' s cytolethal distending toxin (HdCDT) that causes apoptosis and necrosis of human cells such as myeloid cells, epithelial cells, keratinocytes, and primary fibroblasts. [6] The clinical manifestation of these processes is exacerbated by H ducreyi ’s ability to evade phagocytosis, leading to slow healing.
Pustules and ulceration do not manifest in all infected patients. However, in instances when they do develop, it has been described that these individuals mount an exceptional inflammatory response, involving several proinflammatory molecules, namely interleukin 1-beta, at a local level. [5]
For an unknown reason, macrophages in ulcers have greater CCR5 and CXCR4 chemokine receptors, which are used for human immunodeficiency virus (HIV) entry, when compared with cells outside a region of infection. HIV transmission is also facilitated by H ducreyi' s characteristic ulceration and disruption of the epithelium.
Epidemiology
Frequency
United States
Chancroid is noted to be endemic in certain regions of Africa, Asia, and Latin America. In the United States and other developed countries, however, it is essentially unseen at this time. (It is acknowledged that these data may be skewed by underdiagnosis, lack of reporting, and the difficulty in culturing H ducreyi.) In 2019, only 8 cases were reported in the United States involving 5 states. [7]
International
The global incidence of genital ulcer disease is more than 20 million cases per year, with a majority of these cases attributed to syphilis and herpes virus. [8] Even so, in 1997, the annual global incidence of chancroid was reported by the World Health Organization (WHO) and Joint United Nations Programme on HIV and AIDS (UNAIDS) to be about 6 million. [9]
Chancroid is more commonly diagnosed in heterosexual men, minority groups, or impoverished individuals. In addition, chancroid is associated with sexual exposure to a commercial sex worker, drug abuse, and/or alcohol abuse. [10]
Chancroid is more common in less developed areas, areas that are also notable for a greater prevalence of HIV (>8%). Chancroid infection is also commonly seen in individuals co-infected by syphilis or herpes simplex virus, both inside the United States (approximately 10% of patients) and, to a great extent, outside the United States. [8] Other risk factors are low education level, risky sexual behavior, the presence of other sexually transmitted diseases, older age, and male homosexuality. [11]
Given the absence of any determinant publications investigating circumcision and the prevalence of laboratory-diagnosed chancroid, there is still question as to the risk that noncircumcision imparts on these men. In some of these studies, genital ulcerative disease was diagnosed on the basis of clinical presentation without positive culture. In others, there was no direct comparison of study outcomes between uncircumcised and circumcised populations. [12]
Note that the frequency of chancroid, and other bacterial sexually transmitted diseases for that matter, has recently shifted away from bacterial infections and toward viral etiologies such as herpes simplex virus and HIV.
Mortality/Morbidity
If chancroid is diagnosed and treated early, it can be cured easily and quickly. H ducreyi produces painful genital ulcers and tender, enlarged inguinal lymph nodes known as buboes. These may rupture, after forming abscesses, and subsequent scarring may be permanent. Open sores secondary to H ducreyi infection also facilitate the transmission of HIV. Immunocompromised patients, such as those infected by HIV, have lower cure rates and can have more serious complications. [13]
Sex
The male-to-female ratio is between 3 and 25:1, [9] depending on the geographic region being studied. Although males are affected more often, female sex workers appear to harbor the disease.
Age
Mean patient age is 30 years.
Prognosis
Chancroid can be cured with early antibiotic treatment in immunocompetent patients. If chancroid has already progressed to later stages, or if the host is immunocompromised, treatment may fail, resulting in any of the aforementioned complications.
Patient Education
Topics of patient education should include, but are not limited to, condom use, regular genital self-examination, risky behaviors, and informing past and present partners.
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This photograph shows an early chancroid on the penis, along with accompanying regional lymphadenopathy. Courtesy of the CDC/Dr. Pirozzi.
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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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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.
