Chancroid 

Updated: Aug 05, 2019
Author: Joseph Adrian L Buensalido, MD; Chief Editor: Pranatharthi Haran Chandrasekar, MBBS, MD 

Overview

Background

Chancroid is a bacterial sexually transmitted disease (STD) caused by infection with Haemophilus ducreyi. It is characterized by painful necrotizing genital ulcers that may be accompanied by inguinal lymphadenopathy. It is a highly contagious but curable disease.

Chancroid was once highly prevalent in many areas of the world, but collaborated efforts in increasing social awareness and subsequent changes in sexual practices, along with improved diagnosis and treatment options, have eradicated chancroid as an endemic disease in industrialized countries.[1] In 2000, the proportion of chancroid among genital ulcerative diseases (GUD) decreased from 69% to 15%.[2] It remains prevalent in certain underdeveloped regions such as Asia, Africa, and the Caribbean.[2] However, despite the presence of joint STD/HIV control programs, prevention control methods have not been consistently implemented.[1] In these areas, outbreaks occur in cities among workers in the sex trade. Individuals traveling to these high-risk areas are at risk of contracting the disease. In addition, individuals from high-risk areas who travel to other countries to work in the sex industry remain a source of outbreaks in the industrialized world.

Chancroid is a subclass of sexually transmitted genital ulcerative diseases that are of worldwide concern owing to their role as cofactors in the transmission of HIV.[3, 4, 5, 6] Ulcerative STDs penetrate the skin of the external genitalia, colonize the subcutaneous tissue, and produce tissue damage, causing ulceration.[7] Skin abrasion and microtrauma is necessary to penetrate normal skin. The disruption of the mucosal barrier increases the risk of HIV access to the bloodstream and inflammatory cells and serves as a focus for bacterial and viral shedding.[8] A report from the World Health Organization (WHO) estimates that the presence of ulcerative STDs increases the risk of HIV transmission by 10%-50% in women and 50%-300% in men.[9] Multiple genital ulcers, purulent ulcer base, and multiple genital ulcerative lesions increase the likelihood of HIV shedding.[10]

Recently, the etiologic agent of chancroid, H ducreyi, has been isolated among chronic limb ulcers in the Asia Pacific region. H ducreyi should be considered as a cause of chronic limb ulcers in endemic areas[11, 12] and as a common cause of nongenital cutaneous ulcers, mostly in children in tropical countries, especially the South Pacific region.[2]

This photograph shows an early chancroid on the pe This photograph shows an early chancroid on the penis, along with accompanying regional lymphadenopathy. Courtesy of the CDC/Dr. Pirozzi.

See 20 Signs of Sexually Transmitted Infections, a Critical Images slideshow, to help make an accurate diagnosis.

Pathophysiology

Chancroid is caused by H ducreyi, a small, gram-negative, facultative anaerobic bacillus that is highly infective. It is pathogenic only in humans, with no intermediary environmental or animal host. H ducreyi enters the skin through disrupted mucosa and causes a local inflammatory reaction. It produces a cytocidal distending toxin that appears to be responsible for its destructive effects.

H ducreyi penetrates the skin through breaks in the mucosal barriers and microabrasions on the skin. It produces a cytocidal distending toxin (HdCDT), which causes cell cycle arrest and apoptosis/necrosis of human cells and contributes to the aggravation of ulcers.[13] Phagocytosis by macrophages is also impaired.[14, 15] Other virulence mechanisms include LspA proteins, which have antiphagocytic functions, DsrA map, which facilitates adherence, and an influx transporter that protects H ducreyi from antimicrobial killing.[16, 17, 18]

H ducreyi is transmitted sexually by direct contact with purulent lesions and by autoinoculation to nonsexual sites, such as the eye and skin. The organism has an incubation period of 1 day to 2 weeks, with a median time of 5-7 days. The disease typically begins as a small inflammatory papule at the site of inoculation; within days, the papule may erode to form an extremely painful deep ulceration. Without treatment, the lesions may last weeks to months, and complications such as suppurative lymphadenopathy are more likely.[4, 19, 20]

Epidemiology

Frequency

United States

The Centers for Disease Control and Prevention (CDC) collects data from state health departments in the United States and has published information regarding prevalence of STDs, including chancroid, since 1941, when 3,384 cases were reported. Starting in 1994, a significant decrease in the number of chancroid cases was reported. Only 782 cases were recorded in 1994 and steadily decreased over the following years. In 2010, 24 cases were reported from 9 different states, while, in 2013, only 10 cases of chancroid were documented.[21] In 2017, a total of 7 cases were reported.[22]

In the past, the disease was considered endemic in several large US cities but is currently seen in sporadic cases associated with low socioeconomic status, poor hygiene, prostitution among sex workers, and drug abuse. The true incidence is difficult to determine and is probably underestimated because of unavailable diagnostic resources and because of the difficulties in culturing H ducreyi, even when laboratory resources are available.[23]

International

Chancroid is still endemic in many areas of the world. No specific monitoring for this disease exists. The unavailability of diagnostic tests and facilities in resource-limited settings and the difficulty in isolating the organism are recognized factors that contribute to the underreporting of the disease. Therefore, the true incidence of chancroid at present worldwide is unavailable.

Data from the WHO in 1995 suggested that 7 million cases of chancroid existed worldwide. Globally, it has been surpassed by herpes simplex virus (HSV) type 2 as the most common genital ulcerative disease. Chancroid is prevalent in Africa, the Caribbean basin, and Southwest Asia. It is thought to be the most common cause of genital ulceration in Kenya, Gambia, and Zimbabwe.[24, 25, 26] Recently, the prevalence of chancroid decreased substantially in the Philippines, Senegal, and Thailand. This development was probably brought by joint programs against HIV/AIDS and related STDs in those areas.[27]

Local outbreaks in various parts of Europe have been reported. The Health Protection Agency in the United Kingdom reported 450 cases of chancroid from 1995-2000. From 1995-2005, 3% of genital ulcer cases from an STD clinic in Paris were due to chancroid.[28] The European Centre for Disease Prevention and Control released a surveillance report on sexually transmitted infections in Europe from 1990-2010, and it was noted that the prevalence of chancroid had decreased dramatically, that some countries had no reported cases, and that some countries even stopped mandatory notifications.[29]

Mortality/Morbidity

Chancroid is not a lethal disease and does not cause systemic infection, not even in individuals with HIV infection.[30] Even if left untreated, the genital lesion resolves spontaneously within 1-3 months. However, untreated infection can lead to development of painful inguinal lymphadenopathy, which can ulcerate to form buboes in 25% of cases. It is characterized by one or more painful genital ulcers that are associated with unilateral painful inguinal lymphadenopathy in approximately 50% of cases. Left untreated, suppurative bubo formation occurs in approximately 25% of cases, which can progress to spontaneous rupture with formation of a deep nonhealing inguinal ulcer.

Chancroid is easily curable with appropriate antibiotic therapy, although patients with HIV infection require longer courses of therapy. The true impact of the disease lies in the well-known association of genital ulcer disease with increased transmission rates of HIV and other STDs. Previous infection does not confer immunity against the disease, and reinfection is possible.[31] Patients with chancroid and HIV coinfection are more likely to experience multiple chronic genital ulcerations and inguinal lymphadenopathy.[32]

Superinfection of lesions, known as phagedenic chancroid, may lead to widespread disfiguring necrosis and may require surgical excision.

Race

Although no proven racial predilection exists, chancroid is most commonly observed in nonwhite people. This observation is not unexpected, given the prevalence of the disease in areas of Africa, Asia, and the Caribbean.

Sex

Chancroid is most commonly observed in nonwhite men who are uncircumcised. A 2006 meta-analysis showed that circumcision is somewhat protective against infection with syphilis and chancroid.[33] Circumcision and its role in HIV and sexually transmitted infection (STI) risk reduction among men who have sex with men (MSM) still needs further investigation.[34] Women represent only 10% of known cases because they are more likely to be asymptomatic carriers.

Chancroid is more commonly identified in individuals of lower socioeconomic status, commercial sex workers, and travellers from endemic areas.[35] According to Benson and Hergenroeder,[35] there have been no reported cases of chancroid among homosexual males, bisexuals, or lesbian females, but recent reports have documented chancroid to occur together with other STIs.[36, 37]

Age

Although it can affect people of any age, chancroid predominantly affects younger sexually active people. The most common age group affected was 21-30 years.[38] Females aged 15-19 years have the highest prevalence among women in the United States, followed by those aged 20-24 years. In males, the highest prevalence is in those aged 20-24 years.

 

Presentation

History

Patients present with extremely painful suppurative ulcers that may be single or multiple. The infection begins as a papule, which quickly progresses to a pustule and subsequent ulcer formation.[39]

An asymptomatic carrier state is common among women. It is more difficult to diagnose chancroid in women than in men. In women with lesions of the vulva, vagina, or cervix, the chief symptom may be dysuria or dyspareunia and might be overlooked as a typical lower urinary tract infection.[40] They may also have a higher incidence of resolution after papule formation without ulcer formation.

Painful inguinal lymphadenopathy with subsequent ulceration, usually unilateral, develops in approximately 50% of patients within 1-2 weeks.

Physical

Lesions

The lesion of chancroid is often termed as a soft chancre because it is not indurated, as opposed to the indurated syphilitic chancre. The lesion begins as erythematous tender papules that become pustular and later erode to form an extremely painful and deep ulcer with soft (in contrast to the chancre of syphilis) ragged margins.

The ulcer base is composed of easily friable granulation tissue that is usually covered with malodorous yellow-gray exudates.

Ulcers may be single or multiple, and as many as 10 ulcers have been reported on a single patient.

Men more commonly present with single ulcers, whereas women typically have multiple lesions. “Kissing ulcers” occur when one ulcer spreads the infection to the opposite skin surface. Kissing ulcers can form on the lips of the labia majora.

Individual ulcers vary in size from 1-20 mm, with 1-2 cm being the most common size.

In circumcised men, lesions are most commonly found on the coronal sulcus. In uncircumcised men, the lesions are commonly found on the prepuce. Lesions may be obscured by a painful phimosis in uncircumcised men.

In women, lesions are most commonly found on the fourchette, labia, vestibule, clitoris, cervix, and anus. Women may not have not external sores but may present with dysuria, dyspareunia, and vaginal or rectal discharge.

In both men and women, adjacent lesions may merge and form confluent lesions.

Superinfection of ulcers, especially fusospirochetal, may occur and cause deep, necrotic, and gangrenous ulcers. The infection rapidly spreads to subcutaneous and deeper tissues, leading to rapid destruction of the external genitalia, known as phagedenic chancroid.

Lymphadenopathy

Painful, usually unilateral, regional lymphadenopathy occurs in an approximately 50% of patients and is more common in men. Of patients with lymphadenitis, 25% may have progression to a suppurative bubo, which may rupture spontaneously and ulcerate. If untreated, chronic draining sinuses may follow.

Other types of chancroid

Chancroid lesions may not manifest as the usual tender nonindurated ulcers. Some other manifestations of chancroid have been observed, as follows:

  • Transient chancroid produces an ulcer that rapidly resolves in 4-6 days, followed 10-20 days later by a suppurative lymphadenitis.
  • Dwarf chancroid manifests as one or several herpeslike ulcerations, with or without inguinal lymphadenopathy.
  • Follicular chancroid produces ulcerations of the pilar apparatus in hair-bearing areas.
  • Giant chancroid consists of multiple small ulcerations, which coalesce to form a single large lesion.

Pseudogranuloma inguinale

Pseudogranuloma inguinale is another chancroid variety that closely resembles granuloma inguinale caused by Klebsiella granulomatis. Isolation of H ducreyi from lesions differentiates it from granuloma inguinale.

Causes

Chancroid is an STD that results from direct contact with H ducreyi from infected lesions. Risk factors include residing in an endemic area, lower socioeconomic status, prostitution (especially among commercial sex workers), and drug abuse. The incidence of chancroid in circumcised males is lower than that in uncircumcised males, suggesting circumcised men are at lower risk for this disease.[41]

 

DDx

Diagnostic Considerations

Herpes simplex and syphilitic chancre are the most common causes of genital ulcers. The documented decline in chancroid prevalence should be interpreted with caution owing to difficulty in isolation of H ducreyi. It should still be considered, especially in patients who have travelled to or are from endemic areas. Given this limitation, the Centers for Disease Control and Prevention (CDC) has proposed a case definition for probable chancroid, once all of the following criteria are met:[42]

  • One or more painful genital ulcers
  • Presentation and physical appearance of ulcers and lymphadenopathy typical of chancroid
  • No evidence of Treponema pallidum infection on darkfield examination of ulcer exudate and/or serological evidence at least 7 days after ulcer onset
  • Polymerase chain reaction (PCR) or culture of ulcer exudate negative for herpes simplex virus (HSV)

Other infectious causes include lymphogranuloma venereum and granuloma inguinale. Noninfectious causes include psoriasis, trauma, Behçet syndrome, and fixed drug eruptions.[43]

Differential Diagnoses

 

Workup

Laboratory Studies

No laboratory testing is able to immediately confirm the diagnosis of chancroid.[3]

A definitive diagnosis of chancroid is based on isolation of H ducreyi on special media, but such tests are not readily available in many centers. In addition, lesion culture is inaccurate owing to the fastidious nature of the organism, with a sensitivity of less than 80%.[44, 45]

The nucleic acid amplification test (NAAT) is a multiplex PCR assay that yields a high detection rate,[46] although, no molecular assays have been cleared by the Food and Drug Administration (FDA) for use in the United States.[22]

The role of polymerase chain reaction (PCR) in rapid detection of H ducreyi is promising and may supersede culture in diagnosis.[44, 47]

Other Tests

When possible, every patient with chancroid should be tested for the other common STDs (syphilis, HSV, gonorrhea, chlamydia) and HIV.

Procedures

Needle aspiration and/or incision and drainage are recommended for buboes that are fluctuant and tender. As with other abscesses, incision and drainage may be a superior technique for preventing abscess recurrence.

Histologic Findings

Gram stain of the ulcer exudates may reveal short, plump, gram-negative rods in the classic school of fish appearance. Ulcer biopsy should reveal 3 distinct zones. The most superficial zone contains erythrocytes, fibrin, necrotic tissue, and neutrophils. The next zone consists of marked endothelial cell proliferation and many thrombosed new blood vessels. The deepest layer is characterized by a dense infiltrate of plasma and lymphoid cells.

 

Treatment

Medical Care

Treatment should be started as soon as the diagnosis of chancroid is suspected on clinical grounds owing to the lack of appropriate, fast, and sensitive laboratory tests.

The presence of an STI has long been recognized as a risk factor for the acquisition of an additional STI. Patients presenting with suspected or diagnosed chancroid should undergo complete evaluation for other possible concomitant STDs and receive appropriate antimicrobial therapy for the eradication of H ducreyi and the treatment of other more common STDs. The syndromic approach to the treatment of STIs was adopted because of the presence of coinfections with other STIs and HIV.[48]

Appropriate treatment of chancroid cures the infection, reduces the complications, and prevents transmission. The CDC’s 2015 Sexually Transmitted Diseases Treatment Guidelines and the UK National Guideline for the management of chancroid recommends the following antibiotic options:[49]

  • Azithromycin - 1 g orally (PO) as a single dose or
  • Ceftriaxone - 250 mg intramuscularly as a single dose or
  • Erythromycin base - 500 mg PO 3 times daily for 7 days or
  • Ciprofloxacin - 500 mg PO twice daily for 3 days

Azithromycin and ceftriaxone as single-dose treatments have the advantage of observed compliance.

Ceftriaxone is the treatment of choice in pregnant women, although data have suggested that ciprofloxacin presents a low risk to the fetus during pregnancy with potential toxic effects during breastfeeding.[50]

Sexual partners of patients with chancroid should be examined and treated regardless of the presence of symptoms if they had sexual contact within 10 days preceding the onset of symptoms.

Surgical Care

Drain fluctuant lymph nodes with either needle aspiration or incision.

Activity

Patients should abstain from unprotected sexual intercourse while undergoing treatment.

 

Medication

Medication Summary

The goal of therapy is the eradication of the organism and improvement of the patient's symptoms. In addition, prevention of transmission to other individuals is imperative. Circumcision has been shown to reduce incidence of chancroid in men.[33] Considerations for medical treatment include pregnancy, HIV status, and compliance. Medication to cover multiple STDs should be instituted. The syndromic management of genital ulcer disease (GUD) is being used as a principle in the treatment of chancroid in the tropics, and the medications recommended are very effective.[51]

Antibiotics

Class Summary

Therapy must be comprehensive and cover all likely pathogens in the context of the clinical setting.

Azithromycin (Zithromax)

Treats mild-to-moderate microbial infections.

Ceftriaxone (Rocephin)

Third-generation cephalosporin with broad-spectrum gram-negative activity. Lower efficacy against gram-positive organisms. Higher efficacy against resistant organisms. Arrests bacterial growth by binding to 1 or more penicillin-binding proteins.

Erythromycin (E.E.S., E-Mycin, Eryc, Ery-Tab, Erythrocin)

Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. For treatment of staphylococcal and streptococcal infections.

Ciprofloxacin (Cipro)

Fluoroquinolone with activity against pseudomonads, streptococci, MRSA, Staphylococcus epidermidis, and most gram-negative organisms, but no activity against anaerobes. Inhibits bacterial DNA synthesis and, consequently, growth.

 

Questions & Answers