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Chancroid is a sexually transmitted disease caused by the organism Haemophilus
ducreyi.1,2 It is characterized by painful
genital ulcers and tender inguinal adenopathy that may suppurate.
Also known as “soft chancre,” chancroid is one
of the three major causes of genital ulcer disease among young sexually active
patients in the United States; the other major causes are genital
herpes and syphilis.
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Chancroid is a common cause of genital ulcer disease throughout
the world but is not commonly reported in the United States. Although the
prevalence of chancroid is low in the United States, the reason
for this low prevalence may be due to underdiagnosis. Most clinicians do
not have clinical experience with chancroid and thus do not consider
it in the differential diagnosis. Most laboratories do not have
the capability of isolating H ducreyi. Chancroid was
more prevalent in the past (eFig. 258.1).3 Chancroid
cases peaked to a high of 5001 in the United
States in 1988; however, cases have steadily declined with the lowest
number, 17, in 2005, and only 33 cases reported in 2006.3 In
comparison, there were 9756 cases of primary or secondary syphilis reported
in 2006.3 Of the cases in 2006, 12 were in males
and 21 were in females. They were reported from just 8 states with
most (82%) from southern states: 14 from South Carolina,
5 from North Carolina, 5 from Texas, and 1 case each from Louisiana,
Virginia, and Florida. The remaining 6 cases were from New York
and Michigan.
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Other data suggest that the disappearance of chancroid in the
United States may be due to lack of testing and underreporting.4-11 In
a survey of 405 sexually transmitted disease (STD) clinics, only
32 (8%) tested patients for chancroid.4 Surveys
in California from 1996 to 2003 found that less than 300 tests for
chancroid were done, accounting for less than 0.1% of all
tests done for STDs.5 However, in genital ulcer
studies where testing for H ducreyi was done, chancroid
has frequently been found. In a study in Brooklyn, New York, H ducreyi was
identified in 27 of 65 (42%) cases in which a microbiologic
diagnosis was established.6 Coinfection with syphilis
was common. In New Orleans, Louisiana, similar findings were found
in 299 men with nonsyphilitic genital ulcer disease; 39% had H
ducreyi, 19% had herpes simplex virus (HSV), and
the culture was negative in 41%.11 Using the
sensitive polymerase chain reaction (PCR), it appears that chancroid
may be even more common than previously thought. In a PCR study
in Jackson, Mississippi, 59% of genital ulcer cases were
due to H ducreyi.7,8 In another
PCR study in STD clinics in 10 cities in the United States, H
ducreyi accounted for a large proportion of genital ulcer
cases.9 Cases of chancroid were identified in Memphis and
Chicago and accounted for 12% to 20% of genital
ulcer. In 10 patients with chancroid in Memphis, none were identified
clinically. Thus, the burden of chancroid in the United States is
unknown.
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Chancroid is extremely common in certain developing countries.
It is a major cause of genital ulcer disease in sub-Saharan Africa and
in many parts of southeast Asia and Latin America.12-15 Definitive
epidemiologic data are not generally available in these resource-poor
countries because diagnosing chancroid is extremely problematic.
Epidemiologic studies, primarily from Africa, demonstrate that the
presence of genital ulcer disease, much of which may represent chancroid,
is strongly associated with an increased risk of heterosexual transmission
of human immunodeficiency virus (HIV).
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Chancroid should be considered in high-risk groups such as prostitutes,
drug users, and travel to a part of the world where chancroid is
endemic. As many as 10% of patients with chancroid are
coinfected with syphilis or herpes simplex virus (HSV).16
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Clinical Features
and Differential Diagnosis
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The incubation period of chancroid is 3 to 10 days.16-19 The
first lesion is generally a small papule that is surrounded by erythema.
Within 2 to 3 days, a pustule forms that ruptures and leaves a circumscribed
ulcer with ragged, undermined edges without induration (Fig. 258-1). The base of the ulcer is painful,
has an erythematous base with a granular appearance, and usually
is covered with a gray or yellow purulent exudate that bleeds when
scraped. A typical chancroid ulcer is about 1 to 2 cm in diameter,
but the size is variable, especially in HIV-infected patients.20 Often, infected
persons have more than one ulcer. In men, the most common sites
for the ulcers are on the distal prepuce, the mucosal surface of
the prepuce on the frenulum, or in the coronal sulcus. In women,
the majority of lesions are at the entrance to the vagina,
the labia, or perianal areas. With vaginal or cervical lesions,
there may be no symptoms. Unilateral painful tender inguinal adenopathy
is present in as many as 50% of patients. Involved lymph
nodes may become fluctuant to form painful buboes and if untreated
may rupture, forming inguinal ulcers (eFig. 258.2).
Adenopathy is less common in women. Most buboes arise 1 to 2 weeks
after the appearance of the primary ulcer.
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As with other STDs, coinfection with HIV may result in atypical
manifestations of chancroid. There may be numerous lesions, extragenital
involvement, and delays in resolution after treatment.20,21
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The differential diagnosis of genital ulcer disease in sexually
active persons is broad and is greatly influenced by the geographic
location in which the infection was acquired. Worldwide, the main
infectious causes of genital ulcer disease are HSV (genital herpes), Treponema
pallidum (syphilis), Hemophilus ducreyi (chancroid), Chlamydia
trachomatis (lymphogranuloma venereum), and Klebsiella
granulomatis, formerly known as Calymmatobacterium
granulomatis (donovanosis or granuloma inguinale). In the
United States, most cases are due to HSV, followed by syphilis and
chancroid. Noninfectious causes include drug eruptions and Behçet
disease. In the United States, the combination of a painful ulcer
with tender inguinal adenopathy is suggestive of chancroid, and
when accompanied by suppurative inguinal adenopathy is almost pathognomonic.
However, patients with H ducreyi infection may
have ulcers that can be confused with other causes of genital ulcer
disease such as HSV or syphilis; as many as 10% with chancroid
may be coinfected with T pallidum or HSV.
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Diagnostic Evaluation
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Diagnosis of chancroid on clinical grounds alone is difficult
because the presentation is often not classic, and many clinicians
have little experience with the disease. Definitive diagnosis requires
isolation of the organism from a genital ulcer or involved lymph
nodes.2 However, the organism is fastidious and
is difficult to isolate. For culture, a swab should be used to obtain
material from the purulent base of an ulcer (undermined edge after
removing superficial pus) and should be plated directly onto culture
medium.22,23 The material should be cultured on
special media (GC agar base contained 1% to 2% hemoglobin,
5% fetal bovine serum, and 3 ug/mL vancomycin)
that is not widely available. Sensitivity of culture is ~75% compared
to PCR.13,24 Gram stain of purulent material may be
misleading because most genital ulcers are polymicrobial; therefore,
it is not recommended as a diagnostic test.
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Given the low sensitivity of culture, alternative non-culture-based
diagnostic tests have been evaluated. Serologic assays lack sensitivity
during the acute infection and are not available commercially. Most
promising are PCR-based techniques. These assays have high sensitivity
and identify patients with chancroid, from whom bacterial cultures
for H ducreyi are negative. Multiplex PCR assays
that can simultaneously amplify and subsequently detect DNA from H
ducreyi, T pallidum, and HSV from genital ulcer specimens
are undergoing field trials and show promise. Multiplex PCR
was found to have a sensitivity of 95% and 98% in
studies conducted in Lesotho and New Orleans,13,24 with
a specificity of 99.6% in the series from New Orleans.
PCR offers similar advantages for the diagnosis of HSV and syphilis.23 Although
there is no FDA-approved PCR test for H ducreyi in
the United States, some commercial laboratories have PCRs for H
ducreyi.2
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Even if chancroid is diagnosed definitively, it is recommended
that patients also be tested for HIV, and if the initial test is
negative, retesting for both syphilis and HIV 3 months later.16
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The Centers for Disease Control and Prevention (CDC) criteria
make a definite diagnosis of chancroid only with isolation of H ducreyi from
a lesion. A probable diagnosis is made if there are clinical findings
compatible with the diagnosis (painful genital ulcer and tender,
suppurative, inguinal adenopathy) with a negative dark-field microscopic
examination for T pallidum, a negative serologic
test for syphilis, and a negative culture for HSV or a clinical
presentation not typical for herpes.2 Even
with careful evaluation, the sensitivity and specificity of using
clinical criteria for diagnosing chancroid are limited. In a study conducted
in South Africa, the diagnostic accuracy of clinical criteria by
experienced clinicians for laboratory-confirmed cases of chancroid
was only 42% in men and 57% in women.12 Similarly,
in a study in New Orleans, the diagnosis of chancroid by strict
clinical criteria was very specific (94%) but lacked sensitivity
(34%).11 In a study in Lesotho, chancroid
was the clinical diagnosis in 80% of patients with genital
ulcer disease, and in this study, the sensitivity was high (95%);
however, the specificity was poor at 29% for culture and
41% for PCR.13 Because there is a lack
of rapid and reliable diagnostic tests and typically treatment consists
of single-dose therapy, treatment decisions for chancroid are generally
based on a clinical diagnosis. Even if chancroid is diagnosed definitively,
it is recommended that patients also be tested for HIV, and if the
initial test is negative, retesting for both syphilis and HIV 3
months later.16
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Successful antimicrobial treatment of genital ulcers caused by H
ducreyi cures infection, resolves clinical symptoms, and
prevents transmission to others.2 However, in cases
of extensive ulcerative disease, scarring may result despite successful
antimicrobial therapy. A number of agents have been used and are
recommended for the treatment of chancroid including erythromycin, trimethoprim-sulfamethoxazole,
ciprofloxacin, ceftriaxone, and azithromycin. The CDC currently
recommends 1 of 4 antibiotic regimens for treatment of chancroid:
azithromycin: 1 g orally in a single dose; ceftriaxone: 250 mg intramuscularly
in a single dose; ciprofloxacin: 500 mg orally twice a day for 3
days; or erythromycin base: 500 mg orally 3 times a day for 7 days.2
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All 4 regimens are effective for treatment of chancroid in patients
with HIV infection. Ciprofloxacin is contraindicated in pregnant
and lactating women. A successful response to therapy is usually
evident within 48 to 72 hours, as evidenced by decreased ulcer tenderness
and pain. Complete healing of ulcers may take up to 28 days, but
is often achieved in 7 to 14 days. Clinical improvement of ulcerative
disease without lymphadenitis usually occurs shortly after treatment
is initiated. Relief of pain is noted by most patients within 48
hours, and objective improvement in the ulcers is usually evident
within 72 hours. Patients should be reexamined 3 to 7 days after
beginning therapy. If no clinical improvement is evident after 7
days, the diagnosis may be incorrect or the patient could be coinfected with
syphilis, HIV, or other agents.2 Other considerations
include poor adherence with medications or that the organism may
be resistant to the regimen prescribed.2
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Prior to effective antimicrobial therapy, failure to aspirate
fluctuant buboes was associated with the development of draining
fistulas or secondary ulcers at the site of the ruptured buboe.
Even since the availability of antimicrobials agents for chancroid,
healing of fluctuant adenopathy has been shown to be slower than
that of the ulcers and may require needle aspiration through adjacent
intact skin. In a study of 35 patients with inguinal lymphadenitis,
8 of the patients developed fluctuance that required needle aspiration
despite successful treatment of the genital ulcer with erythromycin.25 In
a small study performed during a chancroid epidemic in New Orleans,27 patients
with inguinal buboes were randomly assigned to either needle aspiration
or incision and drainage.26 Both groups ultimately
did well without any adverse events during the period of follow-up,
but the patients managed with needle aspiration often required repeated aspirations.
Thus, either modality can be used to treat fluctuant lymphadenitis
associated with chancroid. In advanced cases, scarring may result
despite eradication of infection.2
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Response may be delayed in some patients. In uncircumsized men,
healing is slower with ulcers under the foreskin. Patients with
HIV infection must be closely monitored, as they may require longer
courses of treatment than the standard regimens outlined above.
Treatment failures have been observed with several of these regimens,
and there is some suggestion that those individuals who are most
immunosuppressed are at the greatest risk for failure of standard
regimens. The erythromycin 7-day regimen appears to be most successful
in HIV-infected persons.
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To prevent further spread of H ducreyi disease,
it is critical to identify all sexual contacts of infected individuals.
The CDC recommends that all persons who have had sexual contact with
a patient with proven H ducreyi infection within
the 10 days before onset of the patient’s symptoms should
be examined and treated.2,16 The examination and
treatment of contacts should be administered even in the absence
of symptoms.2 Standard precautions are recommended.16 Regular
condom use may decrease transmission.16