Chancroid overview

# Overview
Chancroid is a sexually transmitted disease caused by Haemophilus ducreyi, a fastidious Gram-negative coccobacillus. There are 3 classes of this bacteria, 2 of which cause genital ulcer disease and 1 that may be the cause of cutaneous limb ulcers. Pathogenesis involves secretion of 2 virulence factors: fimbrialike proteins (Flp) responsible for adhesion and H. ducreyi cytolethal distending toxin (HdCDT) which cause DNA double-stranded breaks that lead to cell cycle arrest and apoptosis in epithelial cells, fibroblasts, and lymphocytes. Chancroid must be differentiated from other diseases that cause genital ulcers and lymphadenopathy including syphilis, herpes simplex, dermatologic aspects of Behcet's disease, dermatologic manifestations of Lymphogranuloma venereum, donovanosis, and fixed drug eruption. The characteristic manifestation of chancroid is a painful, nonindurated ulcer. The ulcer looks similar to a syphilitic chancre. Approximately 50% of patients (predominantly in males) develop painful inguinal lymphadenopathy, known as buboes. Chancroid can be classified according to its clinical variants identified during a physical examination. Such variants include: dwarf, giant, follicular, transient, serpiginous, mixed, and phagedenic. Chancroid symptoms typically develop 4 to 10 days after infection. Lack of rapid and reliable laboratory tests make diagnosis and treatment decisions based on microbiologic findings difficult. Available laboratory tests involve acquiring a sample of ulcer exudate and include: Gram stain, culture, and multiplex Polymerase Chain Reaction (M-PCR). UNAIDS and the World Health Organization estimate the global incidence of chancroid to be approximately 6 million cases per year. Chancroid is a common cause of genital ulcer disease in developing countries, and is also prevalent in areas of crack cocaine use and prostitution in developed countries. The mainstay of therapy for chancroid is antimicrobial therapy with a single dose of Azithromycin or Ceftriaxone. Special considerations must be taken with patients who are HIV positive or with women who are pregnant or breastfeeding. Methods of primary prevention include: limiting the number of sexual partners, especially those who are prostitutes, using a barrier method of contraception, avoiding traveling to endemic areas of chancroid and prophylaxis with azithromycin. The goal of secondary prevention is to stop the spread of disease. Therefore infection individuals should abstain from sexual intercourse until symptoms reside.

# Historical Perspective
Chancoid has been known to humans since the time of the ancient Greeks. Chancroid was first differentiated from syphilis by Leon Bassereau in 1852. Augusto Ducrey identified Haemophilus ducreyi as the causative organism for chancroid in the 1890s.

# Pathophysiology
Chancroid may develop after transmission of Haemophilus ducreyi through breaks in human epithelium, most commonly through sexual contact. Fimbrialike proteins, Flp1, Flp2, Flp3, are suspected to form pili that assist in adhesion and microcolony formation. H. ducreyi induces secretion of interleukin-6 (IL-6) and interleukin-8 (IL-8), which causes inflammatory cells to form abscesses, leading to the formation of papules that may progress into pustules. H. ducreyi cytolethal distending toxin (HdCDT) is a major virulence factor that contributes to necrosis of myeloid and epithelial cells, causing ulceration. Associated conditions include: coinfection with Human Immunodeficiency Virus (HIV), since HIV and H. ducreyi facilitate each others infection, and coinfection with Treponema pallidum, since syphilis is shown to commonly occur with chancroid. On microscopic examination, a three-zone structure is typical.

# Causes
Haemophilus ducreyi is a fastidious Gram-negative coccobacillus causing chancroid, a gential ulcer disease. A genetically distinct non-sexually transmitted strain may also cause cutaneous limb ulcers.

# Classification
Chancroid may be classified according to its clinical variants identified during a physical examination. Such variants include: dwarf, giant, follicular, transient, serpiginous, mixed, and phagedenic.

# Differential Diagnosis
Chancroid must be differentiated from other diseases that cause genital ulcers and lymphadenopathy including syphilis, herpes simplex, Behcet's disease, lymphogranuloma venereum, donovanosis, and fixed drug eruption.

# Epidemiology and Demographics
UNAIDS and the World Health Organization estimate the global incidence of chancroid to be approximately 6 million cases per year. Chancroid is uncommon in developed countries but may be prevalent in areas of crack cocaine use and prostitution. Chancroid is a common cause of genital ulcer disease in developing countries. Lack of diagnostic testing and difficulty of culturing H. ducreyi make true incidence difficult to determine, therefore potentially leading to under-diagnosis of chancroid in both developed and developing countries. The male to female ratio of patients with chancroid ranges from 3:1 in endemic areas to 25:1 during outbreak situations. Chancroid is common in areas with high rates of Human Immunodeficiency Virus (HIV) infection because HIV infection is a risk factor for acquiring H. ducreyi.

# Risk Factors
Risk factors for chancroid include: multiple sex partners, unprotected sexual intercourse, travel to endemic areas in developing countries, lack of circumcision in males, and infection with Human Immunodeficiency Virus (HIV).

# Natural History, Complications, and Prognosis
Chancroid symptoms typically develop 4 to 10 days after infection. Initial indication of infection involves formation of erythematous papules which develop into pustules after several days. Approximately 1-2 weeks after pustule formation, the lesions may ulcerate. Patients typically develop 1 to 4 ulcers. Lymphadenopathy develops in approximately half of patients, predominantly in males, 1 to 2 weeks after appearance of the primary ulcer. In approximately 25% of patients with lymphadenopathy, lymph nodes may swell to form fluctuant buboes which may rupture and form giant ulcers. Prognosis is poor without treatment. Complications from chancroid include: superinfection of lesions, extensive adenitis, development of inguinal abscesses, and nonhealing ulcers.

# Diagnosis

## History and Symptoms
The characteristic manifestation of chancroid is a painful, nonindurated ulcer. The ulcer may range from 1/8 to 2 inches in diameter and has irregular and sharp borders. Ulcers may discharge a grey/yellow exudate. Other symptoms include painful inguinal lymphadenitis (predominantly in males), known as buboes, and dysuria and dyspareunia in females. Probable cause of chancroid also includes negative tests for Treponema pallidum or syphilis and Herpes Simplex Virus (HSV).

## Physical Examination
Patients may present with erythematous papules, pustules, or ulcers depending the stage of the chancroid. Ulcers are soft with irregular but sharp margins, and looks similar to a syphilitic chancre. Males typically have 1 ulcer while females typically have multiple. The most common location in males is the foreskin (prepuce). The most common location in females in the labia majora. Approximately 50% of patients may present with swollen inguinal lymph nodes.

## Laboratory Findings
Lack of rapid and reliable laboratory tests make diagnosis and treatment decisions based on microbiologic findings difficult. Available laboratory tests involve acquiring a sample of ulcer exudate and include: Gram stain, culture, and multiplex Polymerase Chain Reaction (M-PCR).

## Other Diagnostic Studies
There are no other diagnostic studies associated with chancroid.

# Treatment

## Medical Therapy
The mainstay of therapy for chancroid is antimicrobial therapy.  Azithromycin and Ceftriaxone are preferred because these agents offer the advantage of single dose therapy.  Ceftriaxone is the drug of choice for pregnant women.  Patients with HIV may require longer and repeated courses of therapy.

## Prevention
Since there is no vaccine for chancroid, methods of primary prevention include: limiting the number of sexual partners, especially those who are sex workers, using a barrier method of contraception, avoiding traveling to endemic areas of chancroid and prophylaxis with azithromycin. The goal of secondary prevention is to stop the spread of disease. Therefore infected individuals should abstain from sexual intercourse until symptoms reside.